Pharmacetical Chemistry
Syllabus
(As per New ER2020) Pharmaceutical Chemistry
Introduction to Pharmaceutical Chemistry: Scope and objectives
Sources and types of errors: Accuracy, precision, significant figures
Impurities in pharmaceuticals: Source and effect of impurities in Pharmacopoeial substances, importance of limit test, Principle and procedures of Limit tests for chlorides, sulphates, iron, heavy metals and arsenic.
Volumetric Analysis: Fundamentals of volumetric analysis, Acid–base titration, non-aqueous titration, precipitation titration, complexometric titration, redox titration Gravimetric analysis: Principle and method.
Inorganic Pharmaceuticals: Pharmaceutical formulations, market preparations, storage conditions and uses of:
Haematinics: Ferrous sulphate, Ferrous fumarate, Ferric ammonium citrate, Ferrous ascorbate, Carbonyl iron
Gastrointestinal agents: Antacids: Aluminium hydroxide gel, Magnesium hydroxide, Magaldrate, Sodium bicarbonate, Calcium Carbonate, Acidifying agents, Adsorbents, Protectives, Cathartics
Topical agents: Silver Nitrate, Ionic Silver, Chlorhexidine Gluconate, Hydrogen peroxide, Boric acid, Bleaching powder, Potassium permanganate
Dental products: Calcium carbonate, Sodium fluoride, Denture cleaners, Denture adhesives, Mouth washes
Medicinal gases: Carbon dioxide, nitrous oxide, oxygen
Introduction to nomenclature of organic chemical systems with particular reference to heterocyclic compounds containing up to three rings.
viii Pharmaceutical Chemistry
Study of the following category of medicinal compounds with respect to classification, chemical name, chemical structure (compounds marked with*) uses, stability and storage conditions, different types of formulations and their popular brand names
Drugs Acting on Central Nervous System
Anaesthetics: Thiopental Sodium*, Ketamine Hydrochloride*, Propofol
Sedatives and Hypnotics: Diazepam*, Alprazolam*, Nitrazepam, Phenobarbital*
Antipsychotics: Chlorpromazine Hydrochloride*, Halo-peridol*, Risperidone*, Sulpiride*, Olanzapine, Quetiapine, Lurasidone
Anticonvulsants: Phenytoin*, Carbamazepine*, Clonazepam, Valproic Acid*, Gabapentin*, Topiramate, Vigabatrin, Lamotrigine
Anti-Depressants: Amitriptyline Hydrochloride*, Imipramine Hydrochloride*, Fluoxetine*, Venlafaxine, Duloxetine, Sertraline, Citalopram, Escitalopram, Fluvoxamine, Paroxetine
Drugs Acting on Autonomic Nervous System
Sympathomimetic Agents: Direct Acting: Nor-Epinephrine*, Epinephrine, Phenylephrine, Dopamine*, Terbutaline, Salbutamol (Albuterol), Naphazoline*, Tetrahydrozoline. Indirect Acting Agents: Hydroxy Amphetamine, Pseudoephedrine. Agents With Mixed Mechanism: Ephedrine, Metaraminol
Adrenergic Antagonists: Alpha Adrenergic Blockers: Tolazoline, Phentolamine
Phenoxybenzamine, Prazosin. Beta Adrenergic Blockers: Propranolol*, Atenolol*, Carvedilol
Cholinergic Drugs and Related Agents: Direct Acting Agents: Acetylcholine*, Carbachol, And Pilocarpine. Cholinesterase Inhibitors: Neostigmine*, Edrophonium Chloride, Tacrine Hydrochloride, Pralidoxime Chloride, Echothiopate Iodide
Cholinergic Blocking Agents: Atropine Sulphate*, Ipratropium Bromide
Syllabus ix
Synthetic Cholinergic Blocking Agents:
Tropicamide, Cyclopentolate Hydrochloride, Clidinium Bromide, Dicyclomine Hydrochloride*
Drugs Acting on Cardiovascular System
Anti-Arrhythmic Drugs: Quinidine Sulphate, Procainamide Hydrochloride, Verapamil, Phenytoin Sodium*, Lidocaine Hydrochloride, Lorcainide Hydrochloride, Amiodarone and Sotalol
Anti-Hypertensive Agents: Propranolol*, Captopril*. Ramipril, Methyldopate Hydrochloride, Clonidine Hydrochloride, Hydralazine Hydrochloride, Nifedipine,
Antianginal Agents: Isosorbide Dinitrate
Diuretics: Acetazolamide, Frusemide*, Bumetanide, Chlorthalidone, Benzthiazide, Metolazone, Xipamide, Spironolactone
Hypoglycemic Agents: Insulin and Its Preparations, Metformin*, Glibenclamide*, Glimepiride, Pioglitazone, Repaglinide, Gliflozins, Gliptins
Analgesic and Anti-Inflammatory Agents: Morphine Analogues, Narcotic Antagonists; Nonsteroidal Anti-Inflammatory Agents (NSAIDs) - Aspirin*, Diclofenac, Ibuprofen*, Piroxicam, Celecoxib, Mefenamic Acid, Paracetamol*, Aceclofenac
Anti-Infective Agents
Antifungal Agents: Amphotericin-B, Griseofulvin, Miconazole, Ketoconazole*, Itraconazole, Fluconazole*, Naftifine Hydrochloride
Urinary Tract Anti-Infective Agents: Norfloxacin,
Ciprofloxacin, Ofloxacin*, Moxifloxacin,
Anti-Tubercular Agents: INH*, Ethambutol, Para Amino Salicylic Acid, Pyrazinamide, Rifampicin, Bedaquiline, Delamanid, Pretomanid*
Antiviral Agents: Amantadine Hydrochloride, Idoxuridine, Acyclovir*, Foscarnet, Zidovudine, Ribavirin, Remdesivir, Favipiravir
Antimalarials: Quinine Sulphate, Chloroquine Phosphate*, Primaquine Phosphate, Mefloquine*, Cycloguanil, Pyrimethamine, Artemisinin
x Pharmaceutical Chemistry
Sulfonamides: Sulfanilamide, Sulfadiazine, Sulfametho xazole, Sulfacetamide*, Mafenide Acetate, Cotrimoxazole, Dapsone*
Antibiotics: Penicillin G, Amoxicillin*, Cloxacillin, Streptomycin, Tetracyclines: Doxycydine, Minocycline, Macrolides: Erythromycin, Azithromycin, Miscellaneous: Chloramphenicol* Clindamycin
Anti-Neoplastic Agents: Cyclophosphamide*, Busulfan, Mercaptopurine, Fluorouracil*, Methotrexate,-Dactinomycin, Doxorubicin Hydrochloride, Vinblastine Sulphate, Cisplatin*, Dromostenolone Propionate
Preface v
Inorganic Pharmaceutical Chemistry
Introduction of Pharmaceutical Chemistry and Quality Control of Drugs and Pharmaceuticals 2
Organic Pharmaceutical Chemistry
Hypoglycemic Agents/Antidiabetic Agents 213
xii Pharmaceutical Chemistry
Chemistry
Introduction to
and Quality Control of Drugs
and Pharmaceuticals
1 Define Pharmaceutical Chemistry. Give the scope and objectives of it.
☞ Pharmaceutical Chemistry:
It is the branch of pharmaceutical science that deals with the study of chemistry of medicinal substances.
☞ Scope and objectives:
It helps to impart the basic knowledge of the chemical structure, storage conditions and medicinal uses of organic and inorganic chemical substances, used as drugs and pharmaceuticals.
It helps to study pharmacological uses, doses and stability of the drugs.
It helps to study different formulations available in the market with their brand names.
It helps to study impurity testing and basic quality control testing of the drugs and pharmaceuticals.
It is focused on quality aspect of medicine and aims to assure
fitness for purpose of medicinal products.
2 Define the term “pharmacopoeia”. Give its Importance.
☞ Pharmacopoeia:
Pharmacopoeia is the official book of standards published by
respective Governments containing, the list of drugs, pharmaceuticals,
2
their formulae, identification, standardisation, does, uses, etc. The word pharmacopoeia is derived from the Greek Words: ‘Pharmacon’ means a ‘drug’
‘Poeio’ means ‘To make’’
Importance/Object/Need/Purpose/Scope of pharmacopoeia:
To ensure uniformity in composition of drug.
To ensure purity of drug.
To ensure potency of drug.
To study official preparations of drugs.
To refer procedures for testing of drugs.
List of Pharmacopoeia Published:
First edition in 1955
Second edition in 1966
Third edition in 1985
Fourth edition in 1996
Fifth edition in 2007
Sixth edition in 2010
Seventh edition in 2014
Eighth edition in 2018
3 Define ‘Monograph’. Give the contents of monograph.
☞ Monograph:
Monograph means detailed systematic account of the drug with reference to title, synonym, description, category, identification, official preparations, etc.
Contents of Monograph:
The monograph gives following details of an official compound.
Title: It is an approved name of drug or its preparation.
Synonym: It is an alternative name of the drug.
Description: It gives physical description of the substances like crystalline or amorphous nature, colour, odour, taste, etc.
Identification: Qualitative tests, coloured reactions, precipi-
tating tests, gas evolution are used for identification of drugs.
Test for purity: The upper and lower limits of purity are expressed numerically.
Dose and Dosage: The usual dose and route of administration are mentioned. Usual strength may be given for pharmaceutical dosage forms.
Storage: Storage conditions are important to take precautions in relation to effect of atmosphere, moisture heat, light, etc.
Cold – Between 2°C and 8°C
Cold – Between 8°C and 25°C
Warm – Between 30°C and 40°C Excessive heat – Any temperature above 40°C
Solubility: Solubility of the medicinal compounds is expressed as: Approximate solvent volume in ml for 1 gm of solute.
Very soluble – Less than 1
Freely soluble – From 1 to 10
Soluble – From 10 to 30
Sparingly soluble – From 30 to 100
Slightly soluble – From 100 to 1000
Very slightly soluble – From 100 to 10,000
Insoluble – More than 10,000
Limit of Impurities: Limit tests are important to determine
the permissive limits of tolerance.
Container: Specifications of container such as light resistant, well closed, tightly closed hermetically sealed containers are mentioned.
Labelling: Labelling of the drug or pharmaceutical preparations is as per the Drugs and Cosmetics, Act, 1940.
Physical Constants: Physical constants like melting point, boiling point, refractive index, optical rotation, viscosity, etc. are mentioned in pharmacopoeia for standardisation of pharmaceuticals.
Assays: The estimation of percentage purity of the active chemical constituent is known as assay.
The methods of quantitative analysis (assay) are mentioned in pharmacopoeia.
Category: It represents the main pharmacological action/ther-apeutic use of the drug.
4 Define quality control. Give functions and importance of quality control.
☞ Quality Control
It is the day-to-day process of controlling quality of every incoming
material till the finished product quality.
Functions of Quality Control
Analysis of raw materials.
Analysis of packaging materials.
Analysis of in-process products.
Analysis of final dosage forms.
Analysis of batch products (periodic analysis).
Recording the results of analysis in a standard format.
Importance of Quality Control
To avoid toxic and unwanted effects of impurities.
To avoid technical difficulties during manufacturing.
To maintain safety and effectiveness of products.
To maintain product with adequate physical and chemical stability.
To ensure quality drugs for consumption to the patients.
To maintain purity of product and thus protect public health.
To help in maintenance of quality of product with better utilization of labours and machines.
It helps in adjustment and setting of machineries.
It helps in product development and in research with control
over wastes and scraps.
It helps in decreasing the cost of manufacturing so that cost of final product may be decreased.
5 Define quality assurance. Give its functions.
☞ Quality Assurance:
It is the department which includes a total quality control, government regulations, company standards and development of standard operating procedures of analysis.
Functions
Development of standard operating procedures and supply to
every department of the company.
It has a responsibility of “total quality of the products”.
It gives guidelines during adjustment and setting of the machineries.
It helps to maintain quality of products with better utilisation of
labours and machines.
It helps in product development and research.
6 What are different methods used for quality control in pharmacy?
Quality control is to analyse a drug for quality and quantity. Following are various methods used for quality control.
Quality Control Methods
Qualitative analysis B. Quantitative analysis (estimation of % of drug, i.e. assay)
By colour, odour, solubility i. Chemical assay methods
Identification tests a. Volumetric analysis:
Boiling point, melting point • Acidimetry and
alkalimetry
Redox titrations
Precipitation
titrations
Complexometric
titrations
Gravimetric analysis
Estimation of
weight
Photometric methods
Electrochemical methods
Biological assay methods
7 Write in short about (a) “Significant Figures”,
(b) Precision, (c) Accuracy, (d) Absolute Error,
(e) Standard Deviation.
☞ (a) Significant Figures
Significant figures can be defined as the number of digits necessary to express the results of measurement consistent with the measured precision.
It should be clear that zeros are used to denote the significant
part of measurement.
Thus, zero within a number like 25.05 and 1350 are significant as they express the exact quantity while in the quantity 0.00035 kg the zero before the point, is not significant, but shows the order of magnitude of the other digits.
Precision:
The precision means the degree of reproducibility or agreement
between repeated measurements.
Precision is the variability among replicate measurements, i.e how close the values of the results of replicate measurements are to each other.
More the measurements, better is the precision and error will be
smaller.
Accuracy:
An accuracy means closeness of an experimental result with
true value or actual result.
Accuracy is the differences between the true value and the value
of experimental result.
An experimental procedure may be highly precise, but because
of some errors, the results could be inaccurate.
Accuracy expresses the correctness of the measurement.
Absolute Error (Eabs):
“The absolute error of a determination is the difference between the observed or measured value”.
The absolute error is a measure of the accuracy of the measurement.
The absolute error may be positive or negative.
Absolute Error (Eabs) = (X – T), where X – measured or observed value
T – accepted or true value.
Standard Deviation/root mean square deviation (S/SD):
It is one of the most common statistical terms used in analytical
chemistry.
The standard deviation is a measure of how spread-out numbers
is, in other words, it is a measure of precision.
(X X)2
n 1
It is abbreviated as S or SD.
,
SD
where,
n—Number of measurements.
8 Write a note on “errors in analysis”.
☞ Error:
Error is the difference between measured value and true value.
Though the measurements are made by different methods of quality control, systematically and carefully but there is some degree of error.
An error is associated with every measurement.
The analyst must try to reduce the magnitude of the error to an
accepted level.
Determinate errors/systematic errors: These types of errors are determinable and can be either avoided or corrected.
Instrumental error: It is caused by use of faulty equipment.
Personal error: It is the error made by person doing analysis.
Chemical error: This error is due to impurities in chemicals.
Methodological error: It arises due to faulty method used for analysis, e.g. incomplete reaction, incomplete heating.
Indeterminate errors/random errors: These errors are also called accidental errors. These errors are fluctuating and do not have a definite value and are difficult to locate. They arise
due to unknown and uncertain measurement or may be due to
differences in judgment and skill of analyst.
Hence, elimination of these errors is impossible to the analyst.
9 Define impurity. Discuss various sources of impurities in pharmaceutical substances.
☞ Impurity:
Impurity is an undesirable matter which may or may not be toxic but present in the pharmaceutical substances.
Sources of Impurities
Raw material used in manufacture: If raw material contains an impurity, then this impurity gets incorporated into the final product.
Impurities like lead, arsenic, etc. are present in the raw materials and hence found in substances as impurities, e.g. if copper foils are contaminated with arsenic, the final product CuSO4 may contain arsenic impurity.
Reagents used in manufacturing process: If reagents contain impurity, it is transferred to the final product, e.g. calcium carbonate is prepared by using calcium chloride and sodium carbonate. Thus, it may contain impurity of sodium carbonate or calcium chloride.
The process used in manufacturing: There are a number of chemicals which are manufactured from different raw materials by different methods or processes. Due to this some impurities get incorporated into the materials during manufacturing process.
Tap water is generally used in various manufacturing processes. Tap water contains chlorides, calcium, magnesium as impurities thus gets incorporated in the products.
Material of plant: Equipment and vessels used in manufacturing process are made of metals like copper, iron, aluminium, zinc but these metals are introduced as impurities by the solvent action of raw materials. Nowadays, these metals are replaced by stainless steel.
Intermediate products: Incomplete reactions produce unwanted intermediate products which may be the impurity in the final products.
Adulteration/accidental substitution: The cheap substances are added in pure substances as a substitute and, therefore, added substances act as an impurity in pure substance, e.g. sodium bromide is an impurity in potassium bromide as the sodium salt is cheaper.
Inadequate storage/defective storage
Many chemical substances undergo changes due to careless storage, thus may develop impurity in it.
Stored products may become contaminated with dust, the bodies of insects and even animals and insect excreta.
Many substances when exposed to light, air and moisture, may change the colour, properties and shelf life of products, e.g.
Due to careless storage, ferrous sulphate is slowly converted
into insoluble ferrous oxide by air and moisture.
Surgical solution of chlorinated soda deteriorates upon exposure to light and heat. Hence, it should be stored in well closed amber-coloured bottles in cool place.
Chloroform decomposes in presence of light and air and forms a phosgene gas which is toxic. So, it should be stored in well closed amber-coloured bottle.
Bismuth carbonate is blackened on long exposure to sunlight.
Manufacturing hazards: Impurity may get incorporated at various stages of manufacturing.
Particulate contamination: It involves the pieces of plastic, threads in the product and also come from improperly cleaned equipment and also due to wear and tear of equipment.
Process error: It involves incomplete reactions during processing.
Cross-contamination: Handling of powders, granules and tablets may produce considerable air-borne dust. This airborne dust may lead to cross-contamination of other products.
Microbial contamination: Liquids or creams may be contaminated due to bacteria and fungi from atmosphere.
Packing errors: The products of similar appearance such as
tablet of same size, colour and shape may be packed in the
similar containers and can cause danger due to mislabel-ling.
10 What are different types of impurities commonly occurring in pharmaceuticals?
Toxic impurity: If impurity is present above the prescribed limit and produces toxic effect on the body, it is called toxic impurity,
e.g. lead, arsenic impurities.
Harmless impurity: Some impurities are harmless but if present above the prescribed limit, they lower active strength of substances, e.g. impurities of sodium salts in potassium salts.
Impurity affecting storage property: For example, presence of small amount of moisture in the drug may reduce flow property and affect the storage.
Impurity causing technical difficulties: Impurities cause many technical problems during manufacturing, e.g. picking and sticking defects may occur in tablet manufacturing.
Impurities affecting taste, odour and appearance of the product.
Impurities even when present in traces, may show a cumulative
toxic effect after certain period.
Impurity which lowers the shelf life of the substances.
11 Discuss the effects of impurities.
☞ Effects of Impurities:
Impurities may produce toxic effect if present above certain
limits.
Impurities, even in small quantity, may show cumulative toxic
effect after a certain period.
Impurities may reduce active strength of the substance.
Impurities may change physical and chemical properties of the
substance and thus making it medically useless.
Impurities may cause technical difficulties in the formulations.
Impurities may produce incompatibility with other substances.
Impurities may lower the shelf life of the substance.
Impurities may affect and change the colour, odour, taste and
appearance and make the substance unhygienic.
12 Define the term “limit tests”. Explain BSR.
☞ Limit Tests:
These are qualitative tests used to identify the small amounts of impurities present in the substances.
BSR (Barium Sulphate Reagent)
It is used in limit tests for sulphate IP 85.
Composition of BSR
BaCl2 solution.
Sulphate-free alcohol.
Potassium sulphate solution.
Uses of ingredients
BaCl2 reacts with impurity to form BaSO4.
Alcohol prevents supersaturation.
Potassium sulphate increases the sensitivity of test.
13 Describe the limit test for chloride IP.
☞ Principle/Concept:
Chloride impurity reacts with silver nitrate to form a white precipitate of silver chloride in the presence of dilute HNO3. It is observed as opalescence.
Reaction
3
Cl– + AgNO
dilute HNO3
3
AgCl + NO –
Silver nitrate Silver chloride precipitation
Note
Purified water is used for dilution and it is free from dissolved
gas and impurities.
Standard solution is prepared as it gives maximum permissible
limit for comparison.
Dilute HNO3 is used as it avoids the reaction of acidic radicals other than chloride with that of AgNO3.
The opalescence is directly proportional to amount of chloride impurity present in the substance.
If test substance is coloured (KMnO4), then first it is deco-lourised and then followed for limit test.
Procedure
Limit test for chloride IP 66
Test solution
Standard solution
solution.
Weight of substance as per monograph.
1 ml of dilute HNO3.
Dilute up to 50 ml with water.
Add 1 ml of 5% AgNO3
1 ml of 0.01 N HCl solution.
1 ml of dilute HNO3.
Dilute with water up to 50 ml.
Add 1 ml of 5% AgNO3 solution.
Limit test for chloride IP 85
Test solution
Standard solution
Weight of substance as per monograph.
Add 10 ml of dilute HNO3.
Add water up to 50 ml.
Add 1 ml of 1% AgNO3 solution.
1 ml of 0.0585 w/v of NaCl solution.
Add 10 ml of dilute HNO3.
Add water up to 50 ml.
Add 1 ml of 1% AgNO3 solution.
Limit test for chloride IP 96
IP 96 prescribes use of 1 ml of 0.1 M AgNO3 solution. The chloride impurity is generally 25 parts per million. Standard chloride solution is taken 10 ml for the preparation of standard solution.
Stir both the solutions and keep it aside for 10 minutes.
Remarks
If opalescence produced in test solution is less than standard solution, substance passes the limit test for chloride IP.
14 Describe the limit test for sulphate IP.
☞ Principle/Concept:
Sulphate impurity reacts with barium chloride in the presence of dilute HCl to form white precipitation of barium sulphate. It is observed in the form of turbidity.
Reaction
SO – – + BaCl
dilute HNl
BaSO
+ 2Cl–
4 2 4
Barium chloride Barium sulphate precipitation
Note
Purified water is used for dilution and it is free from dissolved
gas and impurities.
Standard solution is prepared as it gives maximum permissible
limit for comparison.
Dilute HCl is used as it avoids the reaction of acidic radicals
other than sulphate with that of BaCl2.
Barium sulphate reagent: It is used according to IP 85. It contains BaCl2, K2SO4 and alcohol. Barium chloride reacts with sulphate impurity. Alcohol prevents supersaturation. Potassium sulphate increases rate of reaction and sensitivity.
Procedure
Limit test for sulphate IP 66
Test solution
Standard solution
Weight of substance as per monograph.
1 ml of dilute HCl.
Add water up to 50 ml.
Add 1 ml of BaCl2 solution.
2.5 ml of 0.01N H2SO4.
1 ml of dilute HCl.
Add water up to 50 ml.
Add 1 ml of BaCl2 solution.
Limit test for sulphate IP 85
Test solution
Standard solution
K2SO4.
Limit test for sulphate IP 96
It prescribes ethanolic sulphate standard solution which gives 10 ppm sulphate impurity and also use of 25% w/v barium chloride solution.
Stir well both the solutions and keep it aside for 5 minutes.
Weight of substance as per monograph.
Add 2 ml of dilute HCl.
Add water up to 45 ml.
Add 5 ml of BSR.
1 ml of 0.1089% w/v of
Add 2 ml of dilute HCl.
Add water up to 45 ml.
Add 5 ml of BSR..
Remarks
If turbidity produced in test solution is less than standard solution, sample comply with the limit test for sulphate IP.
15 Describe the limit test for iron IP.
☞ Principle/Concept:
Iron impurity reacts with thioglycolic acid in the presence of dil. ammoniacal alkaline medium to form purple-coloured ferric thioglycate.
Reaction
Fe++ + 2
CH2 SH
Ammonia
CH2
Fe
SH
+ 2H+
COOH
COO
2
Thioglycolic acid Ferric thioglycate (purple-coloured)
Note
Purified water is used for dilution purpose and it is free from
dissolved gases and impurities.
Standard solution is prepared as it gives maximum permissible
limit for comparison.
Ammoniacal alkaline medium is necessary for reaction of thio-
glycolic acid with iron impurity.
Citric acid prevents precipitation of iron with ammonia.
Thioglycolic acid is used because it reacts with ferrous form of iron and converts it into ferric form. Thus, it forms purple colour.
Procedure
Limit test for iron IP 66
Test solution
Standard solution
alkaline pH.
with water.
alkaline pH.
with water.
Weight of substance as per monograph.
Add 40 ml of water.
Add 2 ml of citric acid (20%).
Add ammonia to adjust
Adjust volume up to 50 ml
2 ml of standard iron solution (0.173 gm of ferric ammonium sulphate + 1.5 ml of HCl).
Add 40 ml of water.
Add 2 ml of citric acid.
Add ammonia to adjust.
Adjust volume up to 50 ml
Limit test for iron IP 85
Test solution
Standard solution
alkaline pH.
with water.
alkaline pH.
with water.
Weight of substance as per monograph.
Add 40 ml of water.
Add 2 ml of citric acid.
Add ammonia to adjust
Adjust volume up to 50 ml
2 ml of standard iron solution (0.1726 gm of ferric ammonium sulphate + 10 ml of 0.1 N H2SO4).
Add 40 ml of water.
Add 2 ml of citric acid.
Add ammonia to adjust
Adjust volume up to 50 ml
Stir well and keep aside for 5 minutes and observe.
Remarks
If purple colour obtained in test solution is less than standard solution, sample passes limit test for iron IP.
16 Describe the limit test for heavy metals IP.
☞ Principle/Concept:
Heavy metal impurity reacts with hydrogen sulphide/sodium sulphide in presence of acidic/alkaline medium respectively to form brown precipitation of metal sulphide.
Reaction
2
M + H S MS + 2H+
M + NaS MS + 2Na++
(Metal sulphides) (brown precipitations)
Note
Purified water is used for dilution purpose and it is free from
dissolved gases and impurities.
Standard solution is prepared as it gives maximum permissible
limit for comparison.
H2S and Na2S solutions are the reactants and require acidic/ alkaline media for their reactions respectively.
Acidic medium is adjusted by ammonia or acetic acid while alkaline medium is adjusted by NaOH.
IP 66 does not have limit test for heavy metals.
Procedure
Method ‘A’
Limit test for heavy metal IP 85
Test solution
Standard solution
As per monograph 25 ml solution prepared.
Add dilute acetic acid/ ammonia to adjust the pH between 3 and 4.
Add water up to 35 ml.
Add 10 ml of H2S solution.
Dilute it up to 50 ml with water.
Take 2 ml standard lead solution and dilute it up to 25 ml.
Add dilute acetic acid/ ammonia to adjust the pH between 3 and 4.
Add water up to 35 ml.
Add 10 ml of H2S solution.
Dilute it up to 50 ml with water.
Stir well and keep aside for 5 minutes. Observe and compare the brown colour produced.
Remarks
If brown colour obtained in test solution is less than standard solution, sample passes the limit test for heavy metal IP 85.
17 Describe the limit test for arsenic.
☞ Principle/Concept:
Arsenic impurity is converted into arsine gas which further reacts with mercuric chloride paper to form yellow stain of mercuric arsenide.
Reactions
Arsenic is converted into arsenic acid.
As H3AsO4
Arsenic acid is converted into arsenous acid.
H3AsO4 H3AsO3
Arsenous acid is converted into arsine gas.
H3AsO3 + 6[H] AsH3 + 3H2O
(Arsine gas)
Arsine gas is converted into mercuric arsenide.
AsH2
Note
2AsH3 + HgCl2 Hg
AsH2
+ 2HCl
Purified water is used for dilution purpose and it is free from
dissolved gases and impurities.
Standard solution is prepared as it gives maximum permissible
limit for comparison.
Lead acetate cotton plug is used to avoid the interaction of
hydrogen sulphide gas with mercuric chloride.
Stannated zinc is used for slow and steady evolution of nascent
hydrogen.
Time required for the preparation is more therefore, this test
should be observed after 40 minutes.
All reagents should be having AST grade (free from arsenic).
Procedure
Limit test for sulphate IP 85
Test
Standard
Substance as per monograph.
Add 1 gm of KI.
Add 10 gm of stannated zinc
0.2 to 1 ml standard arsenic solution.
Add 1 gm of KI.
Add 10 gm of stannated zinc
Shake the bottles and keep aside for 40 minutes.
Remarks
If yellow stain obtained in test mercuric chloride paper is less than standard stain, sample passes limit test for arsenic IP 85.
18 Describe apparatus used for limit test for arsenic.
Explain Gutzeit test apparatus.
☞ Gutzeit Test Apparatus
Construction
It consists of a wide-mouthed glass bottle of capacity 120 ml.
Glass tube of 200 mm length is passed in it through the rubber
bungs.
Glass tube is constricted at lower end.
It has a 2 mm hole.
The end of the tube should be above the liquid.
Mercuric chloride paper is sandwitched between two rubber bungs and fixed by clip.
Lead acetate cotton plug is inserted into the glass tube before
operation.
19 What do you mean by “Test for Purity”? Explain various ‘Tests for purity’ as per pharmacopoeia.
☞ Tests for Purity:
These are the tests used to detect the undesirable impurities in the substance.
☞ Following are the Tests for Purity:
Colour and odour:
These tests are used only when other tests for purity are not applicable. These tests are valuable to know whether the substance is reasonably aesthetic and hygienic or not.
Physical constants:
Melting point, boiling point, refractive index, optical rotation are suitable physical constants. In the presence of impurities variations are observed in these constants.
Humidity:
The amount of moisture in the atmosphere is called as humidity. Moisture content of medicinal substances is determined.
Insoluble constituents:
It helps to detect the impurities in the substances.
Organic impurities:
Organic impurities may be from raw material or intermediate products or by products in the reaction.
Acidity or alkalinity:
Excess of acidity or alkalinity has an effect and keeping qualities of the compounds.
So, some important tests are used to determine the purity of medicinal substances.
Anions:
Acids like H2SO4 and HCl are widely used in the manufacture of medicinal substances. Therefore, chloride and sulphate are commonly present as impurity in many of the medicinal substances.
4
Hence, tests for anions like Cl–, SO – are prescribed in official
books.
Cations:
Tests for cations include the tests for sodium, potassium, ammonium radical and heavy metals like iron, lead, copper, etc.
Ash:
The reside left after complete ignition (incineration) of the
drug is called as ash.
Determination of ash value is performed to have the idea
about the contents of foreign cations and heavy metals.
In organic compounds, the alkali salts are generally present as impurities. In such cases the determination of ash value is preferable.
Ash value is useful to judge the identity or purity of crude
drugs.
Ash value helps in detecting the adulteration and substitutions in crude drugs.
Arsenic/Lead:
Arsenic and lead both impurities are toxic in nature. So, their presence in medicinal compound is controlled by performing the limit test for arsenic and lead.
Loss on drying (LOD):
In this test, absorbed water or water of hydration is determined by drying under specified conditions.
Loss in weight due to drying also represents the residual volatile constituents including organic solvents as well as water.
Loss on ignition (LOI):
This type of test is applied to stable substances, which are liable to contain thermolabile impurities.
For example, contamination of light magnesium oxide by carbonate is controlled by performing this test.
This test is applied to two classes of substances:
Those which are completely volatile when ignited
Those which undergo a major decomposition, leaving a residue of definite composition.
20 Give the difference between: “Determinant and Indeterminant errors”.
☞
Determinant Errors (systematic errors) | Indeterminant Errors (random errors) |
|
|
Analysis
1 Define the terms:
Accuracy: An accuracy means closeness of an experimental result with true value or actual result.
Precision: The precision means the degree of reproducibility or agreement between repeated measurements.
Assay: The estimation of percentage purity (the potency) of the active principle in the unit quantity of a medicinal compound is called as an assay.
Direct Titration: When solution of unknown strength under determination is titrated directly with the titrant and volume of titrant used till end point is directly proportional to the quantity of the substance under determination, it is called as direct titration, e.g. assay of sodium bicarbonate, ferrous sulphate.
Indirect titration: When of the substance under determination cannot be titrated directly with the standard solution but treatment with some simple chemical treatment is capable of formation a proportional amount of a substance which can be directly titrated with a titrant, it is called as an indirect titration, e.g. assay of ammoniated mercury, copper sulphate.
Back/Residual titration: When the substance under determination is either unstable or volatile or the rate of reaction is slow, it is treated with the known excess volume of a suitable standard solution for a complete chemical reaction and excess of unreacted standard solution is determined by a suitable titrant, it is called as back/residual titration, e.g. assay of sodium chloride by modified volhard’s method.
24
Volumetric analysis (titrimetric analysis): Volumetric analysis involves the determination of volume of standard solution that reacts quantitatively and completely with the solution of the substance to be determined.
Gravimetric analysis: The gravimetric analysis means the substance to be analysed is converted into a definite chemical composition, by using a suitable reaction, seperated in this dried component, the purity of a substance is found out.
Iodimetry (iodimetric) titration: Iodimetry is a volumetric analysis involving either titration with a standardized solution of iodine (free iodine solution).
Iodometry (iodometric) titration: Iodometric is the quantitative analysis of a solution of an oxidizing agent by addition of an iodide that reacts to form iodine. Or iodometric is the quantitative analysis method where the iodine is liberated during the reaction and is titrated.
Titrate: The substance to be determined is called as the titrate.
Titrant: The substance of known concentration is called titrant.
Titration: The process of determining the volume is called titration.
Indicator: Some auxiliary substance that is used to detect the end point of titration is called as the indicator.
End point: The point at which the reaction is complete is called the end point.
Standard solution: The solution of known concentration is known as the standard solution.
Molarity (M): It can be defined as the number of moles of
solute present in one litre of the solution.
Normality (N): It is the number of gram equivalent of solute present in one litre of solution.
Normal solution: A solution containing 1 gm equivalent weight per thousand ml of solution.
Molar solution: A solution containing 1 mole per thousand ml of solution.
2 What do you mean by “Qualitative and Quantitative analysis”?
Qualitative Analysis: It involves the detection and identification of the constituents of the sample.
Quantitative Analysis: It deals with the determination of exact quantity of pure constituent present in a sample or a mixture of substances.
Quantitative analysis is carried out by the following methods:
Volumetric (titrimetric) analysis
Gravimetric analysis
Instrumental analysis
Gasometric analysis
Another method of quantitative analysis based on size of the sample used for analysis:
Macroanalysis – Sample of more than 0.1 gram.
Semi-microanalysis – 10 to 100 mg of sample.
Microanalysis – 1 to 10 mg of samples.
Ultra-microanalysis – Samples of the order of a micro-
grams (mg = 10–6gm).
3 Define volumetric (Titrimetric) Analysis. Classify different methods of volumetric analysis.
☞ Volumetric Analysis: It involves the determination of volume of standard solution that react quantitatively and completely with the solution of the substance to be determined.
☞ Classification/Methods of Volumetric analysis:
Acid–base titrations (neutralisation titration):
When the neutralisation reaction is involved, then the titration is called as acid–base titration or neutralisation titration,
2
e.g. NaOH + HCl ® NaCl + H O.
Redox titration:
Chemical reactions involving oxidation–reduction are widely used to analyse the various samples (oxidants and reductants),
e.g. 10 FeSO + KMnO + 8 H SO
® 5 Fe (SO ) + K SO +
4 4 2 4
2 MnSO4 + 8 H2O.
2 4 3 2 4
Precipitation titration:
The formation of the precipitate in the reaction involved,
2
e.g. AgNO3 + NaCl ® AgCl + NaNO
Complexometric titrations:
In this type stable complex is formed in the reaction involved. The complexing/chelating agent like EDTA forms complex with various metal ions.
Non-aqueous titrations:
These titrations are when the reactoin takes place in non-aqueous solvents, i.e. organic solvents.
This is mainly used for analysis for very weak acids and bases.
4 Define Assay (Quantitative Assay). What are different types of assay?
☞ Assay: The estimation of the potency of the active principle in the unit quantity of a medicinal compound is called an essay.
☞ Type of Assay:
Chemical assay.
Biological assay.
Immunological assay.
Microbiological assay.
5 Describe in details Acid–base titrations. (Acidimetry and Alkalimetry type titrations.)
☞ Acid–base titrations: The titrations which involve the neutralisation reaction between acid and base forming salt and water are called as acid–base titrations.
2
H+ + OH– ® H O
In this case, acids may be defined as the substances, which when
dissolved in water, undergo dissociation, forming H+ ion.
The base is a substance which when dissolved in water gives
OH– ions.
Commonly used acids in these titrations are HCl and H2SO4 and bases NaOH, KOH, and sodium bicarbonate.
Indicators used in these titrations are called acid–base titrations,
e.g. phenolphthalein, methyl orange, methyl red, and phenol.
Examples of Acid–Base Titrations:
Assay of sodium bicarbonate (baking powder), boric acid, ammoniated mercury, ammonium chloride.
6 Give the principle, reactions involved, procedure of assay of Sodium Bicarbonate. Write a note on assay of Sodium Bicarbonate.
☞ Assay of Sodium Bicarbonate:
Type: Acidimetric method.
Formula: NaHCO3 (direct titration method).
IP Standard: It contains not less than 99% and not more than 101% of NaHCO3.
Principle:
Sodium bicarbonate is titrated by acidimetric method.
Sodium bicarbonate is a salt of strong base NaOH and carbonic acid. Hence, it is dissolved in water.
It gives alkaline solution which is directly titrated with strong acids like HCl using methyl orange as an indicator.
Reactions:
For Standardization:
Na CO + 2 HCl ® 2 NaCl + H O + CO
2 3 2 2
2
2
For Assay:
NaHCO3
Procedure:
+ HCl ® NaCl + H O + CO
For preparation of 1 M HCl:
Take about 8.9 ml of commercial red conc. HCl by burette or measuring cylinder. Add slowly distilled water and stirr it constantly and make the volume up to 100 ml with distilled water. Keep it in a stoppered flask.
For standardization of Hydrochloric Acid:
Weigh accurately 1.5 gm of anhydrous sodium carbonate
previously heated at about 27°C for 1 hour in an oven.
Dissolve it in 100 ml of water in 250 ml conical flask.
Add 0.1 ml of methyl red solution as an indicator.
Titrate slowly against the acid from burette until solution
turns faintly pink.
Heat the solution to boiling, cool and continue the titration until the faint pink colour remain unchanged.
For Assay:
Weigh accurately 1.5 gm of sodium bicarbonate.
Dissolve it in 50 ml of water in a 250 ml conical flask.
Add 0.2 ml of methyl orange solution as an indicator.
Titrate the solution with standardized 1 M HCl until the
solution becomes pink.
Factor for calculation:
For standardization of HCl:
Each ml of 1 M HCl Ξ 0.05599 gm of Na CO
2 3
For Assay:
Each ml of 1 M HCl Ξ 0.08401 gm of Na CO .
2 3
Category: Electrolyte replenisher, systemic alkaliser
Uses:
As a carminative
In treatment of crystalluria
As a systemic alkaliser
In treatment of poisoning.
7 Write a note on “Assay of Boric Acid/Boracic Acid”.
☞ Assay of Boric Acid:
Type: Acid–base titration/alkalimetric method/direct titration.
Formula: H3BO3.
I.P. Standard: It contains not less than 99.5% and not more than 100.5% or H3BO3.
Principle:
Boric acid is based on alkalimetric method.
Boric acid is weak acid, hence it cannot be titrated with
strong alkali like sodium hydroxide.
When boric acid is dissolved in glycerin–water mixture it acts as a strong monobasic acid and can be titrated with standard alkali using phenolphthalein as an indicator.
Reactions:
(a)
(b)
(c) Net Reaction:
Procedure:
For standardization of sodium hydroxide:
Weigh accurately 5 gm of potassium hydrogen phthalate.
Dissolve it in 75 ml of carbon dioxide free water.
Add 0.1 N of phenolphthalein solution as indicator.
Titrate the solution with NaOH till pink colour is produced.
For assay of Boric Acid:
Weigh accurately 2 gm of boric acid as a conical flask.
Add mixture of 5 ml water and 100 ml glycerin, previously neutralized to phenolphthalein solution and dissolve the sample completely.
Add few drops of phenolphthalein indicator and titrate with 1 M sodium hydroxide until the pink colour is produced.
Factor for calculation:
For standardization:
Each ml of 1 M sodium hydroxide Ξ 0.02042 gm of C8H5KO4.
For Assay:
Each ml of 1 M sodium hydroxide Ξ 0.06183 gm of H BO .
3 3
Category: Local anti-infective
Uses:
Used for cleansing of wounds.
Mild antiseptic.
In mouthwash and gargles.
8 Write a note on “Assay of Ammoniated Mercury”.
☞ Assay of Ammoniated Mercury:
Type: Acid–Base titration (indirect titration).
Formula: NH2HgCl.
Principle:
It is based upon acid–base titration.
It is assayed by an indirect method where the substance is
treated to liberate alkali quantitatively.
The sample is dissolved in solution of potassium iodide.
The precipitate of HgCl2 dissolves in excess of potassium iodide with the liberation of equivalent amount of alkalies as ammonia and KOH, which are titrated against standard hydrochloric acid, using methyl orange as an indicator.
Reactions:
NH2HgCl + 2 KI + H2O —® HgCl2 + KCl + KOH + NH3
(Insoluble) (Liberated
alkali)
HgCl2 + 2 KI —® K2HgI4
(Soluble)
NH3 + H2O —® NH4OH
KOH + NH4OH + 2 HCl —® KCl + NH4Cl + 2 H2O
Procedure:
Weigh accurately about 0.25 gm of substance and transfer to a stoppered flask containing 50 ml of water and 3 gm of potassium iodide, shaking occasionally, till it dissolves.
The liberated alkali is titrated against 0.1 N HCl, using methyl orange as an indicator.
2
Factor: Each ml of 0.1 N HCl Ξ 0.0126 gm of NH
Category: Topical antiseptic and disinfectant.
Uses:
As topical antiseptic and disinfectant.
In treatment of psoriasis.
HgCl.
To treat minor skin infections and other skin disorders.
9 Write a note on “Assay of Ammonium Chloride”. I.P. 85.
☞ Assay of Ammounium Chloride
Type: Acid–base titration (indirect titration method)
Formula: NH4Cl
I.P. Standard: It contains not less than 99% and not more than 100.5% of NH4Cl
Principle:
It is based an acid–base titration.
It is assayed by a new (I.P. 1985) indirect titration method.
A weighed quantity of the sample of ammonium chloride is
dissolved in water.
The solution is treated with neutralised formaldehyde solution in a titration flask.
This results in the quantitative liberation of hydrochloric
acid equivalent to ammonium chloride.
This liberated HCl is then titrated with a standard solution of
sodium hydroxide using phenolphthalein as an indicator.
Pink colour produced is an end point of titration.
Reactions:
4 NH4Cl + 6 HCHO ——® (CH2)6 N4 + 4 HCl + 6 H2O
(Ammonium (Formaldehyde) (Hexamine)
Chloride)
4 HCl + 4 NaOH ——® 4 NaCl + 4 H2O
Procedure:
Weigh accurately 0.1 gm of sample, dissolved in 20 ml of water and add a mixture of 5 ml of formaldehyde solution, previously neutralized to dilute phenolphthalein solution and 20 ml of water.
Allow the reaction to take place for two minutes and titrate slowly with 0.1 N sodium hydroxide using solution of phenolphthalein as an indicator.
Appearance of pink colour is the end point.
4
Factor: 1 ml of 0.1 N NaOH Ξ 0.005349 gm of NH Cl.
Category: Expectorant.
Uses:
Used as an acidifying agent.
As a diuretic.
To maintain physiological acid–base balance.
10 Write a note on “Assay of Zinc Oxide”.
☞ Assay of Zinc Oxide:
Type: Acid–base titration.
Formula: ZnO
I.P. Standard: It contains not less than 99% and not more than 100.5% of ZnO.
Principle:
This assay is based on acid–base type of titration.
Zinc oxide reacts with acid very slowly so the back titration
is useful for the assay of zinc oxide.
In this assay the zinc oxide is added to definite amount of a sulphuric acid, which is taken in excess and is titrated with standard solution of sodium hydroxide.
Sulphuric acid solution, which is excess, is back titrated.
From the volume of sulphuric acid consumed, percentage of
zinc oxide can be calculated.
Ammonium chloride is added to prevent the precipitation of zinc hydroxide, which interferes with the end point detection.
Reactions:
Chemical Reaction for Standardization:
Chemical Reaction for Assay:
4
ZnO + H2SO4 ® ZnSO + H2O
2
4
H2SO4 + 2NaOH ® Na SO
+ 2H2O
Procedure:
Standardization of sodium hydroxide:
Weigh accurately 5 gm of potassium hydrogen phthalate.
Dissolve it in 75 ml of carbon dioxide free water in conical flask.
Add 0.1 ml of phenolphthalein as an indicator.
Titrate the solution with given sodium hydroxide.
Continue titration till pink colour appears.
Assay of zinc oxide:
Weigh accurately 1.5 gm of zinc oxide.
Dissolve it with 2.5 gm of ammonium chloride in 50 ml of 1 N sulphuric acid with the add of gentle heat, if necessary.
Add few drops of methyl orange as an indicator.
Titrate the excess sulphuric acid with 1 N sodium
hydroxide.
Factor:
For standardization: Each ml of 1 M sodium hydroxide Ξ
0.02042 gm of C8H5KO4.
For assay: Each ml of 1 N sulphuric acid Ξ 0.04069 gm of ZnO.
Category: Topical protective
Uses:
It is a mild antiseptic and an astringent.
In treatment of eczema, urticaria, sunburns, ringworms.
In combination with other protective or antimicrobial agents.
As a pharmaceutical aid in the manufacture of adhesive tape.
11 What are Redox Titrations/Oxidation–Reduction Titrations ?
☞ Redox Titrations:
A redox titration is a titration in which the analyte and titrant react through an oxidation–reduction reaction.
Oxidation–reduction reactions are used in volumetric determinations.
Oxidation reaction is the reaction where addition of oxygen or
removal hydrogen takes place.
Reduction reaction is the reaction where addition of hydrogen
or removed oxygen.
The principle involved in redox titrations is that the oxidation process involves loss of electrons, whereas the reduction process involves the gain of electrons.
Oxidation and reduction usually occur simultaneously in the reaction, i.e. while oxidising the substance, the oxidising agent itself gets reduced.
The various oxidising agents used in redox reactions are classified as:
Permanganate titrations: Potassium permanganate is used
as an oxidant
Dichromate titrations: Potassium dichromate is used as an
oxidant.
Iodine titrations: Iodine is used as an oxidising agent.
Cerimetry: Ceric salts are used as an oxidant.
Redox titrations are used to determine the concentration of an
unknown solution that contains an oxidizing or reducing agent.
Example of redox titrations: Assay of potassium permanganate, ferrous sulphate, hydrogen peroxide, sodium oxalate, iodine, chlorinated lime, antimony potassium tartrate, copper sulphate.
12 What do you mean by permanganate titrations?
☞ Permanganate titrations:
When potassium permanganate is used as an oxidising agent in volumetric reactions, it is called as permanganate titrations.
Explanation:
Standard solution of potassium permanganate is used as
titrant in this method.
Potassium permanganate is acidic solution acts as an oxidant.
Reaction:
2 KMnO4
+ 3 H2SO4
® K SO
+ 2 MnSO4
+ 3 H2O + 5[0]
2
4
The nascent oxygen thus formed, oxidises the substance.
Thus, potassium permanganate acts as a self indicator.
4
Here potassium permanganate, because of MnO – shows
colour change from purple to pink.
4
When reduced to Mn++, the colour disappears and when the reaction completes, because of excess concentration of MnO –, it shows a pink colour again.
The end point is thus detected.
Potassium permanganate acts as an oxidant in basic and neutral media also.
13 Write a note on “Assay of Ferrous Sulphate”.
☞ Assay of Ferrous Sulphate:
Type: Oxidation–reduction titration (redox/permanganate titration)
Formula: FeSO4.
I.P. Standard: It contains not less than 98% and not more than 105% or FeSO4.7H2O.
Principle:
It is oxidation–reduction type of assay, i.e. redox type of titration.
In this titration potassium permanganate acts as an oxidising
agent.
It reduces FeSO4 and KMnO4, and it self acts as an indicator in this titration.
Ferrous sulphate is directly titrated against standard solution of potassium permanganate in presence of acidic medium by sulphuric acid.
Ferrous salt can be easily oxidised to ferric form under
ordinary condition.
The end point becomes faint pink colour.
Acidic medium is necessary for the reaction and to prevent
precipitation of MnO.
2
4
Reactions:
2 KMnO4
+ 3 H2SO4 ® K SO + 2 MnSO4 + 3 H2O + 5 [0]
4 2 4 4 2
5[2 FeSO
+ H SO + 5[0] ® 5 Fe (SO )3 + 5 H O]
2
4
Net reaction: 2KMnO4 + 8 H2SO4 + 10 FeSO4 ® K SO + 2
MnSO4 + 5 Fe2SO4 + 8 H2O.
Procedure:
Weigh accurately 1 gm of sample.
Dissolve it in 20 ml distilled water in conical flask.
To this add 10 ml dil. sulphuric acid.
Titrate this solution against standardized solution of potassium permanganate.
Factor: Each ml of 0.1 N KMnO4 Ξ 0.0278 gm of FeSO4.7H2O.
Assay of Ferrous sulphate as per I.P. 1985:
Principle:
According to I.P. 85, ferrous sulphate can also be estimated by using ceric ammonium sulphate as a titrant (oxidising agent) and ferroin sulphate as an indicator.
Ceric ammonium oxidises ferrous sulphate in acidic medium
preferably in sulphuric acid medium to ferric sulphate.
2 FeSO + 2(NH )
Ce(SO ) ® Fe (SO )
+ 2(NH ) SO +
4 4 2
Ce2(SO4)3.
4 3 2 4 3
4 2 4
Ferrion sulphate is an indicator used in this titration, which is a solution of O-phenanthroline in aqueous solution of ferrous sulphate.
3 moles of O-phenanthroline combines with 1 ferrous ion to
form complex Fe(C12 H8 N ) having red colour.
2 3
+2
After completion of the reaction with ferrous sulphate, ceric
ammonium sulphate oxidises the indicator to ferric form, Fe(C12
2 2
8
H N ) +3 having blue colour.
12
2 Fe(C12 H8 N2)3 SO4 + 2(NH4)2 Ce(SO4)3 ® [Fe (C H8 N2)3]2
(SO4)3 + 2(NH4)2 SO4 + Ce2(SO4)3.
Ceric ammonium sulphate in sulphuric acid medium is a strong
oxidising agent and considerably more stable than standard potassium permanganate.
Sufficient sulphuric acid is to be used to prevent hydrolysis and
precipitation of basic salts.
Advantages of this system over permangnate titration are:
It is a simple one electron reaction. Fe+2 Fe+3 + e
Ce+4 + e Ce+3
In place of sulphuric acid, hydrocholoric acid may be used. It does not interfere with analytical application.
Procedure of Assay of Ferrous sulphate I.P. 85:
Weigh accurately about 1 gm of substance.
Dissolve it in a mixture of 30 ml water and 20 ml of dilute
sulphuric acid.
Titrate with standard ceric ammonium sulphate. Using ferroin sulphate solution as an indicator.
Factor: Each ml of 0.1 N ceric ammonium sulphate Ξ 0.0278 gm of FeSO4.7H2O.
Category: Haematinic
Uses:
Used as haematinic.
Used in anemias caused due to iron deficiency.
14 Write a note on “Assay of Hydrogen peroxide”.
☞ Assay of Hydrogen Peroxide:
Type: Oxidation–reduction/redox/permanganate titration.
Formula: H2O2.
I.P. standard: It contains not less than 5% w/v and not more than 7% w/v of H2O2, corresponding to about 20 times its volume of available oxygen.
Principle:
The assay of hydrogen peroxide is based upon oxidation–re-duction reaction.
Hydrogen peroxide acts as a oxidising agent and liberates
oxygen rapidly.
However, hydrogen peroxide is titrated with potassium permanganate solution which acts as a reducing agent.
In this reaction potassium permanganate itself acts as self
indicator.
Reaction:
2 KMnO4 + 3 H2SO4 + 5 H2O2 → K2SO4 + 2 MnSO4 + 8 H2O +
5 O2.
A farily high concentration of sulphuric acid is used to reduce the formation of MnO2 and which is a catalyst for the decomposition of hydrogen peroxide.
Usually strength of hydrogen peroxide is represented in
terms of volume strength.
It is defined as the number of ml of oxygen at N.T.P.
1 gm of H O Ξ 329.2 ml of O
2 2 2
Procedure:
Dilute 10 ml of sample solution to 250 ml in volumetric flask.
To 25 ml of this solution, add 10 ml of 5 N sulphuric acid and titrate with 0.1 N potassium permanganate to obtain faint pink colour as the end point.
Factor:
2
2
Each ml of 0.1 N KMnO4 Ξ 0.001701 gm of H O
Category: Antiseptic
Uses:
Antiseptic and disinfectant.
For cleansing wounds.
In mouthwash and gargles.
Topical anti-infective
As antimicrobial agent.
15 Write a note on “Assay of Sodium Oxalate”.
☞ Assay of Sodium Oxalate:
Type: Oxidation–reduction/redox/permanganate titration.
Formula: Na2C2O4.
Principle:
It is based upon redox (permanganate) titration. It is also
called as residual titration.
Sodium oxalate is allowed to react with sulphuric acid to liberate the equivalent amount of oxalic acid, which is titrated against standard solution of potassium permanganate, till the appearance of permanent pink colour, which is the end point.
Potassium permanganate itself acts as an indicator.
The titration should be carried out in acidic medium and at 70°C with constant stirring, otherwise formation of the black precipitate of Mn2O takes place. This precipitate interferes in the accurate detection of end point.
Reaction:
Na C O + H SO ® Na SO + H C O
2 2 4 2 4 2 4 2 2 4
2 KMnO + 3 H SO + 5 H C O ® K SO
+ 2 MnSO
+ 8 H O
4 2 4
+ 10 CO2
Procedure:
2 2 4 2 4 4 2
Weigh accurately about 0.3 gm of sample.
Dissolve it in 25 ml of water and 6 ml of sulphuric acid pre-viosly diluted with water and titrate the solution with 0.1 N potassium permanganate solution.
Factor:
Each ml of 0.1 N kMnO4 ≡ 0.0069 gm of Na2C2O4.
Category: Reducing agent
Uses:
As a reducing agent.
Used to remove calcium ions from blood plasma.
Used as chelating agent and anticorrosive agents.
16 Write a note on “Assay of potassium permanganate”.
☞ Assay of Potassium permanganate:
Type: Oxidation–reduction/redox/permanganate titration.
Formula: KMnO4.
I.P. standard: It contains not less 99% of KMnO4.
Principle:
It is assayed by redox titration/direct titration.
The titration is made with a standard solution of oxalic acid in the presence of sulphuric acid at or 70°C throughout the entire titration.
The solution of potassium permanganate to be assayed is taken in the burette.
The standard solution of oxalic acid and sulphuric acid are taken in the titration flask.
Potassium permanganate itself serves as an indicator.
End point is appearance of permanent pink colour.
Oxalic acid gets oxidised to carbon dioxide by potassium
permanganate.
Reaction:
2 KMnO
+ 3 H SO + 5 H C O ® K SO + 2 MnSO +
4 2 4 2 2 4 2 4 4
8 H2O + 10 CO2 ↑
Procedure:
Weigh accurately about 0.8 gm of sample.
Dissolve it in water and dilute to 250 ml with water.
Titrate this solution with 25 ml. of 0.1 N oxalic acid, mixed
with 25 ml of water and 5 ml of sulphuric acid.
Keep the temperature at about 70°C throughout the titration.
Factor:
Each ml of 0.1 N KMnO4 Ξ 0.00316 gm of H2C2O4. 2H2O.
Category: Antimicrobial agents.
Uses:
It is used as antibacterial, antifungal, germicidal, and astringent properties.
It also has a deodourising action.
Useful in cleansing of wounds, ulcers abscesses.
As a gargles or mouthwashes.
1% solution of KMnO4 is used in bromhidrosis (the secretion of foul smelling perspiration and in mycotic infections such as athlete’s foot.)
A 5% solution has a powerful styptic action.
17 Write a note on Iodine Titrations. Explain Iodometric and Iodimetric type titrations. Give the difference between iodometric and iodimetric titrations.
☞ Iodine Titrations:
Titrations involving reaction with iodine makes use of the oxidising power of iodine in aqueous solution
2
I + 2e → 2I–
Iodine is practically insoluble in water, the iodine solution is prepared by dissolving it in solutions of KI, forming KI3, which acts as free iodide.
This can be easily titrated against standard solution of reducing
agents such as sodium thiosulphate.
Iodine itself can act as self indicator because of its colour.
But in iodine titrations, generally starch solution is used as an
indicator to detect the end point of reaction.
Generally starch absorbs iodine to give insoluble complex.
Starch solution should be added near to the end point, rather than at the initial stages of reaction, to prevent formation of complex of amylopectin, which interferes with the reaction.
End point is bluish to colourless.
Higher temperature and presence of alkalies should be avoided
in the titration to get proper end point.
Types of Iodine Titrations:
Iodimetry (Iodimetric):
Iodimetry is a volumetric analysis involving either titration with a standardized solution of iodine, i.e. when free iodine solution is reacting, e.g. assay of iodine.
Iodometry (Iodometric):
Iodometry is the quantitative analysis of a solution of an oxidising agent by addition of an iodide that reacts to form
iodine, i.e. iodine is liberated during the reaction is titrated, eq. assay of chlorinated lime, assay of antimony potassium tartrate, assay of copper sulphate.
Iodimetry (iodimetric)
Iodometry (iodometric)
It is a direct titration method.
The number of redox reaction is one.
Iodine will get reduced.
Less commonly used in experiments.
Free iodine is titrated.
It is used to quantify reducing agents.
It is an indirect titration method.
The number of redox reactions are two.
Iodine will get oxidized initially and then reduced.
More commonly used in experiments.
Liberated iodine is titrated.
It is used to quantify oxidising agents..
18 Write a note on “Assay of Iodine”.
☞ Assay of Iodine (Iodimetry):
Type: Iodimetry/iodimetric/redox titration.
Formula: I2
Principle:
Assay of iodine is based upon iodimetry (redox) type of titration in which standard solution of iodine is used.
It is directly titrated against the standard solution of sodium
thiosulphate.
Iodine being practically in soluble in water, hence it is dissolved in a solution of potassium iodide which forms poly-iodides (KI3), where free iodine acts as oxidising agent.
This solution is titrated against standard solution of sodium
thiosulphate.
The end point is determined by colour change from blue to
colourless.
Reaction:
2 Na2S2O3 + I2 → Na2S4O6 + 2NaI
Procedure:
Weigh accurately about 0.5 gm sample.
Dissolve it in a solution of 1 gm potassium iodide in 5 ml
water.
Dilute to 50 ml with water.
Add 1 ml of dilute acetic acid and titrate with 0.1 N sodium
thiosulphate, using starch as an indicator.
Factor:
Each ml of 0.1 Na2S2O3
Ξ 0.01269 gm of I (iodine)
Category: Antiseptic
Uses:
In treatment of goitre.
In thyroid deficiency.
As antiseptic.
In fungal infections.
In syphyllis and leprosy.
In asthma.
19 Write a note on “Assay of chlorinated lime”.
☞ Assay of chlorinated lime:
Type: Iodometry/iodometric titration.
Formula: Ca(OCl)Cl.
Principle:
Chlorinated lime is assayed by iodometric titrations.
The aqueous solution is treated with acetic acid in presence
of potassium iodide.
The acetic acid reacts to liberate chloride, which in turn replaces the equivalent amount of iodine.
This iodine liberated is titrated against a standard solution of
sodium thiosulphate, using starch as an indicator.
The end point is disappearance of blue colour.
Reaction:
Ca(OCl)Cl + 2 CH3COOH → (CH3COO)2 Ca + HCl + HOCl
Hypochlorus acid
HCl + HOCl → H2O + Cl2 2 KI + Cl2 → 2 KCl + I2
Procedure:
Weight accurately about 4 gm of sample.
Triturate it in a mortar with successive small quantities of water and transfer it to a volumetric flask.
Add sufficient water to produce 1 litre shake thoroughly.
To 100 ml of this suspension, add 3 gm of potassium iodide, dissolved in 100 ml water, acidify with 5 ml acetic acid and titrate the liberated iodine with 0.1 N sodium thiosulphate, using starch as an indicator.
Titration is continued till disappearance of the blue colour.
Factor:
Each ml of 0.1 Na2S2O3
Ξ 0.003546 gm of Cl
Category: Bleaching agent.
Uses:
Used as bleaching powder.
Used in disinfection.
20 Write note on “Assay of Antimony potassium tartrate.”
☞ Assay of Antimony potassium tartrate:
Type: Iodometric/iodometry titration.
Formula: C4H4O7SbK
Principle:
This assay is based an iodometric titration.
It acts as a solution of potassium acid tartrate and antimony
trioxide.
Antimony is converted to antimony pentoxide with the liberation of hydrochloric acid.
The acid brings the reversal of the reaction and hence sodium bicarbonate, sodium potassium tartrate, borax are used.
End point is rather slow and therefore, to make sure the end
point is reached, shake the solution.
Reaction:
2 C4H4O7SbK + 2 I2 + 3 H2O → 2 KHC4H4O6 + Sb2O5 + 4 HI
Procedure:
Dissolve 0.5 gm sample in 50 ml water.
Add 5 gm of potassium sodium tartrate and 2 gm of borax.
Titrate with 0.1 N iodine, using starch mucilage as an indicator, which is added at the end point of the reaction.
Factor:
Each ml of 0.1 N iodine Ξ 0.01625 gm of C H O SbK.
Category: Emetic
Uses:
Used as an expectorant and emetic.
4 4 7
It acts as anti-schistosomal (in schistosomiasis).
In treatment of kala-azar.
21 Write note on “Assay of copper sulphate”.
☞ Assay of copper sulphate:
Type: Iodometry/iodometric titration.
Formula: CuSO4
I.P. Standard: It contains not less than 98.8% and not more than 101% w/w of CuSO4.
Principle:
It is based on iodometric titration.
In this titration copper sulphate solution is treated with
potassium iodide and acetic acid.
Acetic acid is used to provide pH 4 to 5.5, at which copper
sulphate reacts with potassium iodide to form cupric iodide.
Cupric iodide is very unstable and decomposes to cuprous
iodide and equivalent amount of iodine.
The liberated iodine is titrated against standard solution of
sodium thiosulphate.
The reaction of decomposition of cupric iodide is reversible
and to make it irreversible, potassium thiocyanate is added.
Potassium thiocyanate should be added near to the end point
to avoid adsorption of iodine by cuprous thiocyanate.
Reaction:
CuSO4 + 2KI → CuI2 + K2 SO4 2 CuI2 º 2 CuI + I2
I2 + 2 NaS2O3 → Na2S4O6 + 2 NaI
CuI + KSCN → CuSCN + KI
Procedure:
Weigh accurately 1 gm of sample.
Add 3 gm of potassium iodide, 5 ml of acetic acid.
Titrate the liberated iodine with 0.1 N sodium thiosulphate,
using, starch as an indicator.
Continue the titration till a faint blue colour remains, add 2 gm of potassium thiocyanate, stirr well and continue the titration until the blue colour disappears.
Factor:
Each ml of 0.1 Na S O Ξ 0.02497 gm of CuSO .5H O.
2 2 3 4 2
Category: Antimicrobial agent.
Uses: Used as fungicide, bactericide, algaecide, herbicide.
22 Explain the principle of complexometric Titrations.
☞ Complexometric Titrations:
In this type of titrations, a stable complex is formed in the reaction involved. The complexing/chelating agents like EDTA forms complex with various metal ions.
Complexing agent is any electron donating ion or molecule,
usually called a ligand.
It forms complex with metal ions due to its ability to form one
or more covalent bonds with metal ions.
Complexes are generally called as coordination compounds.
Ligands having more than one electron donating group are called as chelating agents, as they form cyclic structures with metal ions in a manner similar to that of crab’s claw.
The solubility of metal chelates in water depends upon the presence of hydrophilic groups such as –COOH, –NH2, –OH.
The term sequestering agent is applied to chelating agents,
which form water-soluble complexes with metal ions.
Ethylenediamine tetra-acetic acid (EDTA) is a sequestering
agent, which reacts with most polyvalent metal ions.
EDTA is hexadentate ligand having six electron donating groups. But generally disodium salt of EDTA is used as a titrant in the titration.
EDTA is quadridentate ligand.
EDTA forms complex with metal ion at a specific pH only. The
reaction takes place as:
2 Na H V + M º Na (MV) + 2 H+
2 2 2
This H+ liberated in the reaction affects the stability of the complex. To remove H+, generally buffer solution is added.
The metal ion indicator (metallochromic indicator) is used to
detect the end point.
Indicators used in complexometric titrations, e.g. eriochrome black-T, murexide, xylenol orange, catechol violet, etc. These indicators are also called as pM indicators.
Complex formation is mainly based upon maintenance of pH
and hence the addition of buffer solution is important in analysis.
Examples of complexometric titrations:
Assay of calcium gluconate, assay of bismuth oxychloride, assay of magnesium sulphate, assay of zinc sulphate.
23 Write a note on “Assay of calcium Gluconate”.
☞ Assay of calcium Gluconate:
Type: Complexometric titration.
Formula: C12H22O14H2O
I.P. Standard:
It contains not less than 98.5% and not more than 102%
W/W of calcium gluconate.
Principle:
It is based upon complexometric titration.
The sample is treated with hydrochloric acid and to this solution sodium hydroxide is added to maintain pH (about 10).
This solution is directly titrated against standard disodium edetate solution, using screened indicator (mixture of murexide and naphthol green).
The end point is deep blue in colour.
Reaction:
Procedure:
Weigh accurately about 0.8 gm sample and dissolve in
150 ml of water containing 5 ml dil. hydrochloric acid.
Add 15 ml of solution of sodium hydroxide, 40 mg of murexide and 3 ml of solution of naphthol green.
Titrate the solution with 0.05 M disodium edetate until the
solution is deep blue in colour.
Factor:
Each ml of 0.5 M disodium edetate Ξ 0.2242 gm of CaC H
O14.H2O.
Category: Mineral supplement.
Uses:
In treatment of calcium deficiency, hypocalcemia.
As an antidote.
As a mineral supplement.
In hypocalcemic tetany.
12 22
24 Write note on “Assay of magnesium sulphate”.
☞ Assay of magnesium sulphate:
Type: Complexometric titration
Formula: MgSO4
I.P. Standard: It contains not less than 99% and not more than 100.5% of MgSO4.
Principle:
It is based upon complexometric titration.
A well-defined simple complex is formed between magnesium and disodium ethylenediaminetetra-acetate.
Magnesium sulphate forms a stable complex with disodium edetate in the presence of strong ammonia-ammonium chloride buffer.
Direct titration method can be adopted.
Mordant black mixture is used as an indicator.
The end point is the change of colour from pink to blue.
The titration is carried out with 0.05 M solution of disodium
edetate which is taken in the burette.
Reaction:
Mg++ + EDTA → Mg EDTA
complex
Procedure:
Weigh accurately about 0.3 gm of anhydrous magnesium
sulphate.
Transfer it to 250 ml conical flask, add about 50 ml of water, 10 ml of ammonia-ammonium chloride buffer, 0.1 gm mordant black mixture.
Titrate with EDTA until distinct blue colour is appeared.
Factor:
4
Each ml of 0.05 M disodium edetate Ξ 0.006019 gm of MgSO .
Category: Saline cathartic
Synonym: Epsom salt
Uses:
As a saline cathartic.
As an anticonvulsant.
As an antidote in heavy metal poisoning.
As a cholegogue.
Locally used as anti-inflammatory agent.
25 Write a note on “Assay of Bismuth oxychloride”.
☞ Assay of Bismuth oxychloride:
Type: Complexometric titration.
Formula: BiOCl
Principle:
It is based an complexometric titration.
The sample is ignited with sulphuric acid at temperature not more than 500°C to remove chloride, as this chloride interferes with the titration by forming tetrachlorocomplexes.
Sulphamic acid is added to ensure pH between 2–3 and titrated against standard solution of disodium edetate, using catechol violet as an indicator.
Reaction:
Bi+++ + Na H V → Na BiV + 2 H+
2 2 2
(Disodium edetate)
Procedure:
Dissolve 1 gm of sample and ignite with sulphuric acid.
Dissolve the residue in nitric acid and adjust pH with ammonia until catechol violet is blue.
Add 0.2 gm sulphamic acid and titrate against 0.05 M disodium edetate, until the colour changes to yellow.
Category: In cosmetic products.
Uses:
Bismuth oxychloride is used in the formulation of making, nail products, cleansing products, fragrances and hair colouring products.
Bismuth oxychloride imparts a white colour to cosmetic and personal care.
26 Explain the principle of precipitation Titrations. Write a note on precipitation Titration.
☞ Precipitation Titration:
In this type of titration precipitate is formed in the reaction involved, e.g.
AgNO3 + NaCl → AgCl ↓ + NaNO2.
(ppt)
Most common methods involved the precipitation reactions
with silver nitrate with halide ions.
In this case end point can be detected when after addition of
more reagent these is no further precipitation.
Precipitation titrations are mainly argentometry titrations where
silver nitrate solution is used.
Precipitation of mercury salts also can be used in analysis. This
is called as mercurometry.
Precipitation titration methods are classified:
Mohr’s method.
Volhard’s method.
Mohr’s method:
The Mohr’s method of assay depends upon the direct volumetric precipitation titration.
This method is used for analysis of neutral halides.
Titration takes place against silver nitrate by use of potassium
chromate as indicator.
The end point is when a brick red precipitate of silver chromate is obtained.
2Ag+ + CrO – → Ag CrO ↓
4 2 4
Volhard’s method:
The volhard method of assay depends upon indirect volumetric precipitation titration.
In this case, ammonium thiocyanate in conjunction with
silver nitrate is allowed to react.
Excess of silver nitrate is added to the solution in the presence of nitric acid and excess of silver nitrate remaining after the reaction is back titrated with ammonium thiocyanate using ferric ammonium sulphate as an indicator.
Here, a reddish-brown colour is produced at the end point
3
due to formation of ferric thiocyanate complex. Fe3+ + 3 SCN– → Fe (SCN) 4–
Ferric thiocyanate complex
(reddish-brown colour)
27 Write a note on “assay of sodium chloride.” (by Mohr’s method).
☞ Assay of sodium chloride (by Mohr’s method)
Type: Precipitation titration/argentometric titrations.
Formula: NaCl
IP standard: It contains not less than 99.5% and not more than 100.5% of NaCl.
Principle (Mohr’s method):
This assay is based upon argentometric type of titration
where silver nitrate solution is used as titrant.
It is analysed by direct titration of sodium chloride against standard solution of silver nitrate using potassium chromate as the indicator.
The end point is when it gives a brick red precipitate due to
formation of silver chromate.
Reaction:
NaCl + AgNO3 → AgCl ↓ + NaNO3
2 AgNO3 + K2CrO4 → Ag2CrO4 ↓ + 2KNO3
(brick red ppt)
Procedure:
Dissolve 0.25 g of substance in 50 ml of water and titrate the
solution against 0.1 N silver nitrate.
Brick red precipitate is produced as the end point.
Factor:
Each ml of 0.1 N AgNO3 Ξ 0.005845 g of NaCl
Category: Electrolyte replenisher
Uses:
As a electrolyte replenisher.
To maintain isotonicity.
As a diuretic.
In bromide and iodine poisoning.
28 Write a note on “assay of ammonium chloride” (IP 1966) (by Volhard’s method).
☞ Assay of ammonium chloride (by Volhard’s method)
Type: Precipitation titration/argentometry.
Formula: NH4Cl
IP standard: It contains not less than 99% and not more than 100.5% of NH4Cl.
Principle:
The assay is based upon argentometry (precipitation) type of
titration.
In this case, the solution of substance acidified with nitric acid is treated with an excess, but known, quantity of nitrobenzene.
Nitrobenzene protects the reaction of silver chloride precipitate with ammonium thiocyanate.
This reaction mixture (i.e. excess silver nitrate) is now titrated against standard solution of ammonium thiocyanate using ferric ammonium sulphate as an indicator.
Appearance of red precipitate is the end point.
Reaction:
NH4Cl + AgNO3 → AgCl + NH4NO3 + AgNO3
(ppt) (unreacted)
AgNO3 + NH4SCN → AgSCN + NH4NO3
(unreacted)
NH SCN + Fe2+ → [Fe(SCN) ]2+
4
Procedure:
6
Ferric thiocyanate
(brick-red ppt)
Weigh accurately about 0.2 g sample.
Dissolve it in 40 ml water and 3 ml nitric acid, 5 ml nitrobenzene and 50 ml 0.1 N silver nitrate.
Shake vigorously for 1 minute.
Titrate the solution with 0.1 N ammonium thiocyanate, using
2 ml solution of ferric ammonium sulphate as indicator.
Factor:
4
Each ml of 0.1 N AgNO3 Ξ 0.00535 g of NH Cl
Category: Expectorant.
Uses:
Used as an acidifying agent.
As a diuretic.
To maintain physiological acid–base balance.
29 Write a note on “assay of yellow mercuric oxide” (by Volhard’s method).
☞ Assay of yellow mercuric oxide (by Volhard's method)
Type: Precipitation titration (by Volhard’s method)
Formula: HgO
Principle:
This is assayed by precipitation titration.
In this assay mercuric oxide is treated with nitric acid to form mercuric nitrate and this solution is directly titrated against standard solution of ammonium thiocyanate.
Ferric ammonium sulphate is used as an indicator.
The end point is appearance of brick red colour.
Reaction:
HgO + 2HNO3 → Hg(NO3)2 + H2O
2NH4 SCN + Hg(NO3)2 → Hg(SCN)2 + 2NH4NO3
NH SCN + Fe2+ → [Fe(SCN) ]2+
4
Procedure:
6
Ferric thiocyanate
(brick-red colour)
Weigh accurately about 0.4 g sample.
Dissolve it in 5 ml nitric acid and 10 ml of water and dilute
with water to 150 ml.
Titrate this solution with 0.1 N ammonium thiocyanate using
a solution of ferric ammonium sulphate as an indicator.
Factor:
4
Each ml of 0.1 NH SCN Ξ 0.01083 g of HgO
Category: Antimicrobial
Uses:
It has antibacterial action.
Used in eye infections like conjunctivitis.
30 Write a note on “gravimetric analysis”.
☞ Gravimetric analysis
The gravimetric analysis means the substance to be analysed is converted into a definite chemical composition, by using a suitable reaction, separated in a pure form and weighed. From the weight of this dried component, the purity of a substance is found out.
The product to be weighed in this analysis may be obtained by :
Volatilisation or ignition.
Solvent extraction.
Precipitation from solution.
General method used in gravimetric analysis is precipitation.
Precipitation method includes following steps:
Weighing of sample: Weighing of the same must be accurate as it represents total sample.
Dissolution: The weighed sample is now dissolved in a proper solvent to prepare a clear solution.
Precipitation: By adding suitable precipitating agent, the substance is converted to a precipitate. Then it is allowed to stand for 2–3 hours. After that the supernatant liquid is tested for completion of precipitation.
Filtration: Filter papers and different crucibles are used for
filtration and precipitate is obtained.
Washing of precipitate: The precipitate obtained for gravimetric analysis are washed to free them from soluble impurities. Washing can be done by cold or hot water. Dilute solutions of electrolytes are also used for washing of precipitate. Organic solvents are also used for washing which reduces time for drying.
Drying and ignition: The precipitate obtained is dried first at 105°C to 110°C in oven. If neccessary, they are ignited in crucible. The period and temperature of ignition depend upon the nature of the precipitate.
Weighing: The dried precipitate having constant composition is now weighed accurately and from this weight, the purity of original compound can be found out.
31 Write a note on “assay of zinc sulphate”. (by gravimetric method).
☞ Assay of zinc sulphate (by gravimetric method)
Type: Gravimetric method.
Formula: ZnSO4.7H2O
Principle:
Zinc sulphate is assayed gravimetrically.
Zinc sulphate is precipitated as zinc carbonate by addition of
sodium carbonate as precipitant.
Zinc carbonate is not ignited to constant composition as zinc
oxide. It is ignited to constant weight.
Reaction:
2
ZnSO4 + Na2CO3 → ZnCO3 + Na2SO4
ZnCO3
Procedure:
D ZnO + CO ↑
Weight accurately about 1 g sample.
Dissolve it in about 100 ml water and heat the solution to 90°C.
To this hot solution, add solution of sodium carbonate to precipitate zinc completely.
Boil for few minutes and set a side to allow the precipitate to
settle down.
Filter the precipitate in a tared Gooch crucible and wash with
water until free from alkali.
Dry the residue, ignite and weigh.
Factor:
4
Each g of residue Ξ 1.984 g of ZnSO .
Category: Astringent.
Uses:
Used as an astringent.
Zinc sulphate solution (0.25%) used as opthalmic astringent.
Internally used as an antiemetic.
32 Write a note on “assay of magnesium sulphate”. (by gravimetric method).
☞ Assay of magnesium sulphate (by gravimetric method)
Type: Gravimetric analysis.
Formula: MgSO4.7H2O
Principle:
Synonym: Epsom salt.
IP standard: It contains not less than 99% and not more than 100.5% of MgSO4.
Principle:
Magnesium sulphate is analysed by gravimetric analysis.
Magnesium sulphate is precipitated in alkaline medium to magnesium ammonium phosphate by using solute of ammonium phosphate as precipitant.
This precipitate is then ignited to magnesium pyrophosphate
at 1100°C and weighed.
Reaction:
MgSO4 + NH4OH + (NH4)2HPO4 → MgNH4PO4 ↓ + (NH4)SO3
+ H2O
2MgNH4PO4 → Mg2P2O7 + 2NH3↑ + H2O
Procedure:
Weigh accurately about 0.5 g sample and dissolve it in 50 ml
of water.
Add 10 ml of hydrochloric acid and dilute to 150 ml with
water.
Cool it to 0°C, add 25 ml solution of ammonium phosphate
slowly with constant stirring.
Dilute it with ammonia solution, until the solution is just
alkaline to a solution of phenol red.
Add further 10 ml of dilute ammonia solution.
Stirr well, allow it to stand for 4 hours and filter.
Wash the precipitate with a mixture of 1 volume of dilute
ammonia solution and 19 volumes of water.
Discard the filtrate.
Dissolve the precipitate in 50 ml 1 N hydrochloric acid and wash the filter with hot 0.1 N hydrochloric acid.
Combine the solution and washings and dilute to about 150 ml with water add 2 ml solution of ammonium phosphate, add dilute ammonia solution until the solution is just alkaline to phenol red solution.
Add a further 10 ml of dilute ammonia solution, stirr well and allow it to stand for 4 hours and filter.
Wash the precipitate with a mixture of 1 volume of ammonia
solution and 19 volumes of water until free from chlorides.
Dry and ignite to constant weight, at 1100°C.
Factor:
4
Each g of residue Ξ 1.082 g of MgSO .
Category: Saline cathartic
Uses:
Used as saline cathartic.
Parenterally as an anticonvulsant.
Antidote for heavy metal poisoning.
As a cholegogue.
As an enema.
33 Write a note on non-aqueous titrations or give theory/ concept, need, advantages, disadvantages of non-aqueous titrations.
☞ Non-aqueous titrations
The titrations of substances which are carried out using non-aqueous solvents are called non-aqueous titrations.
The solvents used in non-aqueous titrations are:
Benzene, toluene, carbon tetrachloride, acetic acid, ammonia, pyridine
Theory/concept/principle of non-aqueous titrations
Non-aqueous titrations are mainly based upon the Bronst-ed-Lowry theory which suggests that an acid is a substance which donates proton while base is a substance which accepts the proton.
Bronsted-Lowry theory states that an acid dissociates in solution to give a proton and forms a conjugate base and a base combines with the proton from dissociated acid to produce conjugate acid.
An acid donates proton, only when a base is present to accept
this proton and vice versa.
HB —® H+ + B–
Acid Proton Conjugate base
B+ + H+ —® HB+
Base Proton Conjugate acid
Need of non-aqueous titrations
Non-aqueous titrations are needed:
When the analyte is to weak acid or a base to be titrated in
H2O.
When the reactants or products are insoluble in H2O.
When the reactants and products reacts with H2O.
When, titration in H2O does not allow a sharp end point but in a non-aqueous solvent with stronger base than –OH , it is possible to get a sharpen point.
Advantages of non-aqueous titrations
Weak acids and base give poor end points in aqueous titrations
but in non-aqueous titrations they give good end point.
The substances which are poorly soluble in water but soluble in non-aqueous organic solvents can be determined by non-aqueous titrations.
The mixture of two or more acids can be analyzed. The individual acid can give separate end point in different solvents.
Disadvantages of non-aqueous titrations:-
Temperature, moisture and carbon dioxide should be controlled.
Solvents used in non-aqueous titrations are costly.
Volatile solvents such as ammonia can pollute solvent.
Indicators need to be prepared in non-aqueous medium.
Some solvents are harmful if not handled properly.
Examples of non-aqueous titrations
Ephedrine preparations
Tetracycline
Antihistaminics
Codeine phosphates in API formation
34 Explain various types of solvents used in non-aqueous titration? What do you mean by leveling effect and differentiating effect of solvents used in non-aqueous titrations ?
☞ Types of solvents used in non-aqueous titrations
There are four types of solvents used in non-aqueous titrations.
Aprotic solvent:
These are chemically neutral and inert substance.
These have a low dielectric constant.
These are unreactive.
These do not cause ionization of solute.
These do not have reactions with acids and bases.
These are used to dilute reaction mixture, e.g. chloroform, benzene, toluene and carbon tetrachloride.
Protophilic solvents:
These possess high affinity for proton.
Weak acids are normally used as solute.
Strong protophilic solvents convert weak acid to strong acid is known as ‘leveling effect’.
Protogenic solvents:
These are acidic in nature.
They readily donate protons.
Strong protogenic solvents increase the strength of weak
bases.
These solvents exert leveling effect on all bases dissolved in
them.
They have high dielectric constant.
They are ionized because of their strength and ability to
donate proton, e.g. sulphuric acid and acetic acid.
Amphiprotic solvents: These are the solvents which are able to donate as well as accept proton, i.e. they posses both protophilic and protogenic properties, e.g. water, alcohol and weak organic acids.
☞ Effects of solvents used in non-aqueous titrations
In non-aqueous titrations two types of effect of solvents are seen:
Leveling effect:
Weak acids act like strong acid in the presence of strong protophilic solvents as well as weak bases act as strong base in the presence of strong protogenic solvents. This effect is known as ‘leveling effect’ . The solvents are called leveling solvents.
Weak acids and bases are normally used in the presence of strong protophilic (pyridine, liquid ammonia) and strong protogenic solvents (HF, H2SO4) because their strengths are enhanced by these solvents.
Differentiating effect:
In less basic non-aqueous solvents like glacial acetic acid, the dissociation of different acids varies, i.e. dissociation of perchloric acid is more as compared to hydrochloric acid therefore, in glacial acetic acid, perchloric acid acts as a strong acid as compared to hydrochloric acid.
This effect of differentiating between the strengths of acid is called differentiating effect and solvents like glacial acetic acid, which show the effect is called differentiating solvents.
Haematinics
1 Define and classify haematinics. Give the uses of haematinics.
☞ Haematinics
The substances which increase the amount of haemoglobin in the blood are called haematinics.
Haematinics are the substances which are required in the formation of blood and used for treatment of anemias.
☞ Classification of haematinics
Iron and its compounds, e.g. ferrous succinate, ferrous sulphate, ferrous gluconate, ferrous ammonium citrate, ferrous ascorbate and carbonyl iron.
Maturation factor, e.g. cyanocobalamine, hydroxycynocobal-amine.
Miscellaneous, e.g. copper, cobalt and riboflavine.
2 What is anaemia? Give the official compounds, incompatibility storage, actions and uses of iron compounds.
☞ Anaemia
Anaemia means decrease in percentage of haemoglobin or RBCs in the blood.
☞ Official compounds of iron
The following iron compounds are official in IP 1985:
Ferrous fumarate
Ferrous gluconate
Ferrous sulphate
61
Dried ferrous sulphate
Iron and ammonium citrate
Iron sorbitol injection BP
Ferrous succinate BP
Iron dextran injection BP
Official in BP.
Incompatibility: Iron compounds are incompatible with mineral
acids, alkali, alkali-carbonates, tannates.
Storage of iron salts: They undergo oxidation, thus are stored in
airtight containers in cool and dark place.
Actions and uses of iron compounds
In iron-deficiency anaemia
In megaloblastic anaemia
In haemorrhage condition
As haematinics
3 Give the formula, synonym, properties, preparation, official preparations, uses of the following haematinic compounds.
Ferrous fumarate
Ferric ammonium citrate
Ferrous sulphate
Ferrous ascorbate
Carbonyl iron.
☞ (a) Ferrous fumarate
Synonym: Iron(II) fumarate
Formula: C4H2FeO4.
Standard: It is having not less than 93% of C4H2FeO4 which is calculated with reference to the substance dried to constant weight at 105°C.
Preparation: It is obtained by double decomposition in which a hot aqueous solution of ferrous sulphate is added slowly to a solution of sodium fumarate with constant stirring. The sparingly soluble ferrous fumarate gets separated. It is filtered and dried.
Properties:
It occurs as a reddish-orange or reddish-brown powder.
It may be having soft lumps which produce yellow streaks
when crushed.
It is having light odour with astringent taste.
It is slightly soluble in water and alochol.
Storage: It is preserved in well-closed containers.
Uses: It is used as haematinic.
☞ (b) Ferric Ammonium gitrate
It is a iron and ammonium citrate IP.
It is also known as ‘scale preparation’ of iron.
Formula: C6H8FeNO7.
Properties:
It occurs in the form of bright brownish red scales.
It has a slight astringent taste.
It is freely water soluble and insoluble in alcholol.
Uses:
It is used as a source of iron in iron deficiency.
It is also used as an acidity regulator.
☞ (c) Ferrous sulphate
Synonym: Iron vitriol, green vitriol, ferrosi sulphas.
Chemical formula: FeSO4.7H2O
Preparation: It is prepared by adding a slight excess of iron to dilute sulphuric acid. When the reaction slackens, the liquid is concentrated by boiling, filtered and allowed to cool. The crystals of ferrous sulphate are separated and dried at room temperature.
Properties:
Fe + H2SO4 → FeSO4 + H2
It occurs as odourless bluish-green crystals or granules or a pale green crystalline powder.
It is odourless, and taste is metallic and astringent.
It is freely soluble in water but is insoluble in alcohol.
Ferrous sulphate when exposed to air it is oxidised and
becomes brown in colour.
Reactions:
Ferrous sulphate when heated at higher temperature, it
decomposes to ferric oxide, SO2 and H2SO4.
2(FeSO .7H O) D Fe O + SO + H SO + 13H O
4 2 2 3 2 2 4 2
Ferrous sulphate reduces silver and gold salts to their
metals.
Ag+ + Fe2+ → Ag + Fe3+
Mercuric chloride is reduced to mercurous chloride in light.
2HgCl
+ 2Fe2+ → Hg Cl
+ 2Fe3+ + 2Cl–
2 2 2
Ferrous sulphate reacts with sodium carbonate solution
produces effervescence of carbon dioxide. FeSO4 + Na2CO3 → FeCO3 + Na2SO4 FeCO3 + H2O → Fe(OH)2 + CO2 ↑
Storage
It should be stored in tightly closed containers because on exposure to moist air, ferrous sulphate crystals undergo slow oxidation and become coated with brown basic ferric sulphate. Also on exposure to dry air, ferrous sulphate loses some of its water of crystallization.
To retard the oxidation and thus to stabilize the preparation containing ferrous sulphate, dextrose (40%) and dextrose (40%) with hypophospharic acid (0.2%) are used.
☞ Incompatibility
It is incompatible with alkalies, benzoates, phosphates, oxidising agents, lead acetate, potassium iodide.
Uses
It is used as a haematinic.
It is used in the treatment of anaemia caused by iron
deficiency.
It posses some disinfectant property.
Official preparations
Ferrous sulphate tablets.
Ferrous sulphate syrups.
☞ (d) Ferrous ascorbate:
Ferrous ascorbate is a synthetic molecule of ascorbic acid and
iron.
In India, ferrous ascorbate tablet contains 100 mg elemental
iron as ferrous ascorbate with 1 mg of folic acid.
Uses:
It is used for the treatment and prevention of iron deficiency
in anaemia.
It is also used for the treatment of anaemia due to chronic kidney failure.
It is also used to treat iron deficiency-related haemoglobin
disorders.
Market preparations
Ferrous ascorbate + Folic acid tablets.
Ferrous ascorbate tablets.
Ferrous ascorbate and folic acid and zinc tablets.
☞ (e) Carbonyl iron:
Formula: Fe(CO)5
Synonym: Iron pentacarbonyl and iron carbonyl.
Properties:
Carbonyl iron is a highly pure iron.
It occurs as a gray powder.
Under standard condition it is free flowing, straw-coloured
liquid with a pungent odour.
Uses:
Carbonyl iron powder is used to treat iron deficiency and as
an iron dietary supplement.
It also helps in the oxygen transport in the body.
Market preparations:
Carbonyl iron tablet.
Carbonyl iron powder.
Brand names: Feosol (carbonyl Fe), icar C, irco.
4 Write a note on “role of iron in the body”. List out the official compounds and official preparations of iron.
☞ Iron (Fe)
Iron is an essential mineral required for human life.
Most of the iron in the body is found in RBCs.
Iron requirement of an adult is 2–6 g per day.
Iron performs following important functions:
It is involved in the transport of oxygen from lungs to tissue.
It is essential for metabolic processes in the cell.
Iron helps in cell respiration and detoxification.
It is also required for the production of ATP.
It helps to maintain immune system normal.
Iron aids cognitive function.
Iron supports healthy skin, hair and nails.
Iron improves oxygen storage through myoglobin.
The deficiency of iron in the body may produce iron deficiency
anaemia.
The deficiency of iron can be overcome by supplementing the iron using various official formulations:
☞ Official compounds of iron
Ferric amonium citrate.
Ferrous fumarate.
Ferrous gluconate.
Ferrous sulphate.
Ferrous succinate.
Iron phosphate.
☞ Official preparations of iron
Ferrous fumarate tablets.
Ferrous sulphate tablets.
Iron dextran injection.
Ferrous gluconate tablets.
Iron sorbitol injection.
Agents
Acidifying Agents, Protective and Adsorbents, Antacids, Cathartics
1 What are GIT agents? Classify gastrointestinal agents with examples. Classify inorganic compounds acting as gastrointestinal agents.
☞ GIT Agents
The agents which are used to treat gastrointestinal disorders are called gastrointestinal agents.
Classification
Acidifying agents: Dilute HCl.
Antacids: Sodium bicarbonate, aluminium hydroxide gel, calcium carbonate, magnesium trisilicate, magnesium oxide, magnesium carbonate.
Protective and adsorbents: Bismuth subcarbonate, bismuth subgallate, milk of bismuth, kaolin.
Saline cathartics (purgatives/laxatives): Magnesium sulphate, sodium potassium tartrate.
Acidifying Agents
2 Write a note on “acidifying agents”.
☞ Acidifying Agents
These substances which increase the acidity in stomach are called acidifying agents.
Mechanism of Action
These substances increase the acidity in stomach by one of the following mechanisms:
They increase acidic concentration due to acidic nature.
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They increase the acidity in stomach by stimulating the secretory cells of GIT.
Types of Acidifying Agents
Inorganic acidifying agents increase the acidity because they are
acidic in nature, e.g. dilute HCl.
Organic acidifying agents act by increasing the secretion of gastric acid, e.g. glutamic acid.
Explanation
The epithelial cells of gastric mucosa secrete the endogenous HCl and required enzymes which are necessary for digestion. Acidic drugs are mostly absorbed from stomach. If acidic concentration is below 4.5 pH, only activity of pepsin is observed. Pepsin is active at pH range 3.5–5. If secretion of gastric acid is decreased than normal condition is called “hypochlorhydria”. If secretion of gastric acid is totally absent, it is called “achlorhydria.”
Symptoms of Achlorhydria
Abdominal pains, loss of appetite, mild diarrhoea, confusion.
3 Explain the term “achlorhydria”. Write a note on drug used in the treatment of achlorhydria/monograph of dilute HCl.
☞ Achlorhydria
When the secretion of gastric acid is totally absent, the condition is called achlorhydria.
Symptoms
Abdominal pains.
Loss of appetite.
Mild diarrhoea.
Confusion.
Dilute HCl
Synonym: Muriatic acid, spirit of salt.
Standard: It contains 10% w/w of HCl.
Properties
It is a clear, colourless, tasteless, odourless liquid.
It is miscible with water and organic solvents.
Acidic to litmus.
Reacts with iron to change its colour.
Storage: It is stored in well closed, inert glass container below 30°C.
Incompatibility: It is incompatible with alkali, alkaline carbonates, metallic oxides and with salts of silver, mercury and lead.
Uses
Dil.HCl is used in the treatment of achlorhydria.
It is used as an acidifying agent.
It is used in the treatment of anemia with iron therapy.
It is also used in the management of metabolic alkalosis.
Protective and Adsorbents
4 What are protectives and adsorbents? Give their actions and uses or write a note on protectives and adsorbents.
☞ Protectives
These are the substances which protect the exposed surfaces from harmful stimuli, e.g. kaolin, bismuth carbonate.
Adsorbents
The substances which are used to adsorb the gases, toxins and bacteria are called adsorbents, e.g. kaolin, activated charcoal.
Mechanism of Action of Protectives and Adsorbents
These substances are water insoluble and also insoluble in dilute
HCl, alkali.
These substances form a protective layer on innermost wall of
GIT. Therefore, contact of bacterial toxins is prevented.
Thus, stimulation of peristalsis by bacteria is prevented and they
are used in diarrhoea.
Adsorbents have a property to adsorb the bacterial toxins and
also gases thus prevent attack of toxins on GIT.
Frequent elimination of watery stools in diarrhoea can be prevented by protective adsorbents.
Examples
Bismuth subcarbonate, kaolin, activated charcoal.
Applications/Conditions in which Protectives and Adsorbents are used
They are useful in the treatment of diarrhoea.
They are useful in poisoning cases to adsorb the poison.
They prevent GIT irritation.
They prevent entry of microbes in the body by forming protective layer, over the surfaces of the body.
Bismuth Compounds used as Protectives
Bismuth subcarbonate.
Bismuth subnitrate.
Bismuth subgallate.
Milk of bismuth.
5 Describe in details following protectives and adsorbents (a) Bismuth subcarbonate, (b) Kaolin,
(c) Talc, (d) Zinc oxide, (e) Calamine.
☞ (a) Bismuth Subcarbonate
Synonym: Bismuth carbonate, bismuthyl carbonate, bismuth oxycarbonate.
Formula: [(BiO2) CO3]2, H2O
Properties
White odourless, tasteless powder.
Insoluble in water and alcohol, dilute alkali.
Dissolves completely in HCl and in HNO3.
Affected by light but stable in air.
Storage: Store in well closed light resistant container.
Incompatibility: With KI because it forms brown precipitation of bismuth tri-iodide.
Uses
It is used as protective and adsorbent.
As antidiarrhoeal.
Mild antiseptic and astringent.
In treatment of gastric and duodenal ulcers.
As a mild antacid.
In treatment of colitis.
Used in cosmetics (lotions and face powder).
Kaolin:
Synonym: China clay.
Kaolin is categorised as:
Light kaolin.
Light kaolin (natural).
Heavy kaolin (kaolin or China clay).
Properties
White odourless, tasteless powder.
Insoluble in water, dilute alkali and acids.
Available in two forms—heavy and light kaolin.
Impure forms of kaolin contain gritty particles.
Storage: It is stored in well closed containers.
Incompatibility: With vitamins, enzymes and alkaloids.
Uses
It is used as an intestinal adsorbent in enteritis.
In treatment of dysentery and diarrhoea.
In treatment of alkaloidal poisoning.
In treatment of colitis.
In treatment of cholera.
In food-poisoning cases.
It is also used as a clarifying agent.
In dusting powders.
In cosmetic preparations.
As a main ingredient of kaolin poultice.
Talc:
Formula: 3 MgO, 4 SiO2.H2O
Synonym: Soap stone, French chalk.
Description:
Foliated talc is the most desirable form for phamaceutical
and cosmetic purposes.
Talc is made up to hydrated magnesium silicate.
Talc is a softest mineral and has higher degree of free flow
than kaolin.
Properties:
It is a very fine, light, homogenous, white or greyish white
powder with no odour or taste.
It is insoluble in water, dilute mineral acids and alkali hydroxide solutions.
Chemical properties: On heating up to 850–1000°C, talc looses
water and enstatite (Mg4Si4O2), natural mineral is formed.
Storage: Stored in well-closed containers.
Uses:
As a pharmaceutical aid.
As a dusting powder in cosmetics.
As a lubricant in tablet granules.
As a filtering aid for clarifying liquids.
As a distributing medium for elixirs.
Zinc oxide:
Formula: ZnO
Synonym: Philosopher's wool.
Properties:
It is a powder that is soft, very fine.
It is colourless, odourless and tasteless.
It is insoluble in water, alcohol and soluble in dilute mineral acids.
Storage: It absorbs carbon dioxide and moisture from the air, it must be kept in a tightly sealed container.
Uses:
As a mild astringent, antiseptic.
Soothing and protective action on the skin.
Used in sunscreens.
It is used as dental cement.
It is found in lotions, powders, and pastes.
It is used to treat ringworm, eczema, psoriasis and pruritis as well as for plaster formation
Calamine:
Formula: ZnCO3.Fe2CO3 or ZnO, Fe2CO3
Synonym: Prepared calamine.
Properties:
It is a fine pink amorphous powder.
It is odourless and tasteless.
It is insoluble in water and soluble with effervescence in hydrochloric acid.
Storage: Stored in well-closed container.
Uses:
It acts as an antiseptic, mild astringent.
As antipruritic/anti-itching agent due to cooling and soothing effect.
As a sunburn soother.
Topical skin protective.
It is applied to skin as lotions, dusting powders and ointments for its soothing and adsorbent properties.
It is used as a local anaesthetic and antipyretic.
Antacids
6 Define Antacid. Classify antacids. Give properties of
an ideal antacid.
☞ Antacid:
The substances which neutralize the abnormal or excessive acidity in the stomach are called as antacids.
Antacids are used to relieve pain, heart burn and in the symptomatic
management of gastric and duodenal ulcers and reflux oesophagitis.
Classification of Antacids:
Water-soluble (systemic/absorbable) antacids, e.g. sodium bicarbonate.
Water-insoluble (non-systemic/non-absorbable) antacids,
e.g. aluminium hydroxide gel, magnesium hydroxide, calcium carbonate, magaldrate, magnesium trisilicate.
An Ideal requirement of Antacid:
It should neutralise excessive acidity in stomach.
It should not be absorbable.
It should not interfere with digestion.
It should not act as a laxative or cause constipation.
It should buffer in the pH range 4–6.
It should be non-toxic and non-irritant.
It should be palatable and cheap.
It should be stable and easily available.
It should not evolve gas.
It should not cause alkalosis.
7 Write a note on “Combination of Antacid preparations”.
☞ “Combination of Antacid preparations”:
There is no single antacid which is ideal. Therefore, combinations of antacids are used which reduce side effects and give more benefits.
Antacid when given singly produces following complications:
Sodium bicarbonate is quick acting but its side effect is systemic alkalosis.
Sodium-containing antacids may produce hypertension.
Magnesium compounds are contraindicated in patients with renal disorders.
Calcium compounds are contraindicated in patients suffering from renal and cardiac disorders.
Aluminium compounds should not be prescribed in patients having hypophosphatemia.
Aluminium and calcium compounds produce constipation.
Magnesium compounds may show laxative action.
Combination of antacid is used because:
Combination reduces constipation effect of antacids.
Combination produces laxative action.
Some combinations produce specific action and are used for specific purpose.
Combination of drugs produces synergistic action.
Combination also reduces the dose of drug required to produce action.
Examples
Calcium carbonate + aluminium hydroxide gel.
Calcium carbonate + magnesium trisilicate.
Magnesium trisilicate + aluminium hydroxide.
8 Write a note on “Sodium Bicarbonate” (Baking soda).
☞ Sodium Bicarbonate
Synonyme: Baking soda, mitha soda, sodium biocarb, sodium hydrogen carbonate.
Chemical formula: NaHCO3.
Standard: It contains 99 to 100.5% w/w of NaHCO3.
Properties:
It is white crystalline powder with a saline taste.
It is stable in air, but slowly decomposes in moist air.
It is soluble in water and insoluble in alcohol.
Its aqueous solution is alkaline.
The alkalinity increases on storage, agitation or on heating.
On heating it produces CO2.
Method of preparation (solvay process):
Sodium bicarbonate is prepared by the solvay process which
is also called the ammonia soda process.
Strong solution of sodium chloride (strong brine) containing high concentration of ammonia is passed through a carbo-nating tower where it is saturated with carbon dioxide gas under pressure.
The ammonia and carbon dioxide react to form ammonium
bicarbonate.
This ammonium bicarbonate undergoes double decomposition reaction with sodium chloride to form sodium biocar-bonate.
NH3 + CO2 + H2O → NH4HCO2
NH4HCO3 + NaCl → NaHCO3 + NH4Cl
Chemical reactions of sodium bicarbonate:
When sodium bicarbonate is heated in a dry state or in a solution, it decomposes giving sodium carbonate, carbon dioxide and water, which is reversible at room temperature.
Heat
2 NaHCO3
Room temperature Na2CO3 + H2O + CO2 ↑
A solution of sodium bicarbonate is slightly alkaline due to hydrolysis of the bicarbonate ion.
HCO– + H O º H CO + H+
3 2 2 3
The pH of 1% w/v solution of sodium bicarbonate is not
greater than 8.6.
Sodium bicarbonate with mercuric chloride solution gives a
reddish brown precipitate of (HgO).
HgCl2 + 2 NaHCO3 → Hg(HCO3)2 + 2 NaCl
Hg(HCO3)2 → HgO↓+ H2O + CO2
Reddish brown ppt.
When sodium bicarbonate is treated with acids, carbon dioxide is liberated.
NaHCO3 + HA → NaA + H2O + CO2 ↑
(HA-any acid)
(It is useful in preparation of effervescent tablet or ganules)
Uses of Sodium Bicarbonate:
Sodium bicarbonate is used as an antacid as it neutralises the acidity. It is a rapidly acting antacid.
It is used as electrolyte replenisher.
It is used in the treatment of systemic acidosis.
A 3.5% solution in warm water is used as an eye lotion.
5% solution used to soften and remove ear wax.
It is an important ingredient in effervescent antacid preparations.
It is used as an antidote in various poisoning.
A 1 to 2% solution is used as rinsing solution for contact
lenses.
1 to 4% of sodium bicarbonate solution are used as vaginal douches.
Storage: It should be stored in air tight containers.
Incompatibility:
It is incompatible with acids, acid salts, dopamine hydrochloride, alkaloidal salts, aspirin, bismuth salicylate. Sodium bicarbonate enhances the darkening of salicylates.
9 Write a note on “Aluminium Hydroxide gel”.
☞ Aluminium hydroxide gel (Aluminium Hydroxide Mixture B.P.)
Synonym: Hydrated aluminium oxide.
Properties:
It is a white viscous suspension of hydrated aluminium oxide together with varying quantities of aluminium carbonate and bicarbonate.
It contains 3.5 to 4.4% w/w Al2O3.
It may contain peppermint oil or other flavouring agents.
It contains sweetening agents such as sorbitol, glycerin, sucrose and saccharin with suitable antimicrobial agents.
Aluminium hydroxide gel may exibit thixotropic properties.
It has a pH range 5.5–8.
Uses:
It is a slow acting antacid.
It gives symptomatic relief in gastric and duodenal ulcers
and reflux oesophagitis.
It is used in the treatment of hyperchlorhydria.
It is also given in the management of urinary phosphatic calculi.
Dried aluminium hydroxide gel is used externally as mild astringent and desiccant.
Storage: It is stored in air tight containers and avoid freezing.
Incompatibility: Aluminium hydroxide gel interferes with or reduces the absorption of a number of drugs including anticho-linesterase agents, barbiturates, digoxin, quinine, quinidine, warfarin, tetracyclines and vitamins.
10 Write a note on “Calcium carbonate” (prepared chalk).
☞ Calcium carbonate:
Synonym: Prepared chalk, precipitated calcium carbonate.
Chemical formula: CaCO3.
Standard: It contains not less than 98.5% of CaCO3.
Properties:
It is a white, odourless, tasteless, microcrystalline powder, stable in air.
It is practically insoluble in water but its solubility is increased by the presence of any ammonium salt or carbon dioxide.
It occurs as a chalk, lime stone, marble, aragonite and calcite.
It is insoluble in alcohol.
Method of preparation of calcium carbonate:
For antacid purpose, calcium carbonate is prepared by mixing the boiling solutions of calcium chloride and sodium carbonate and allowing the resulting precipitate to subside on cooling.
CaCl2 + Na2CO3 2 NaCl + CaCO3
Antacid reaction mechanism:
The gastric hydrochloric acid consumes solubilised calcium carbonate.
CaCO3 + 2 HCl CaCl2 + H2CO3 H2O + CO2 T
The liberation of carbon dioxide is common discomfort associ-
ated with this antacid.
Calcium carbonate produces constipating effect and so, it is given in combination with magnesium antacid.
Uses:
It is used as an antacid.
It relieves the pain of gastric or duodenal ulcers.
It is used as a chalk and also in the treatment of diarrhoea.
It is also used as a polishing agent in tooth powders.
A preparation of native calcium carbonate is used in homeo-pathic medicine.
Storage: It is stored in well closed, air tight containers.
Incompatibility: It is incompatible with tetracycline. Administration of large dose of calcium carbonate with large amounts of milk can cause milk-alkali syndrome (Burnett syndrome).
Usual dose: 1 gm, 4 to 6 time daily.
11 Give the details of Magnesium Hydroxide.
☞ Magnesium Hydroxide (B.P.)
Formula: Mg(OH)2.
It is having not less than 95.0% and not more than 100.5% of
Mg(OH)2.
Preparation: The magnesium hydroxide obtained in the preparation of milk of magnesia is evaporated to dryness. It is also prepared by treating sea water or other natural brines with sufficient calcium hydroxide to precipitate magnesium as magnesium hydroxide, then washing and drying the precipitate.
Properties: It is a white fine amorphous powder. It is almost insoluble in water yielding a solution which is slightly alkaline. It dissolves in dilute mineral acids. It slowly absorbs carbon dioxide from atmosphere.
Magnesium hydroxide and its tablets have been official in N.F.
Assay: An accurately weighed amount of sample is taken in a
flask. To it 25 ml of 1 N H2SO4 is added. Now the excess of acid
is back titrated with 1 N NaOH using methyl red as an indicator. Each ml of 1 H2SO4 = 0.02917 g of Mg(OH)2
Uses: It is used as an antacid.
12 Write a note on “Magaldrate” as an Antacid.
☞ Magaldrate (Aluminium containing Antacid):
Synonym: Monalium hydrate, hydrated magnesium aluminate.
Formula: Al2H14Mg4.2 H2O.
Standard: It contains the equivalent of 28 to 39% magnesium
oxide and 17 to 25% aluminium oxide.
Magaldrate N.F.: It is a chemical combination of aluminium hydroxide and magnesium hydroxide.
Properties:
Magaldrate N.F. occurs as a white, odourless, crystalline
powder.
It is insoluble in water and alcohol.
Usual dose: 400 to 800 mg as required, preferably taken between meals.
Official preparations:
Magaldrate oral suspension N.F.
Magaldrate tablets N.F.
Uses:
As antacid.
In the treatment of oesophagitis, duodenal and gastric ul-
cers of gastroesophageal reflux.
Used to treat heart burn, indigestion or stomach upset.
Brand name: Ron acid, Riopan, Ri-Mag, Losospan.
Cathartics
13 Define cathartics. Classify cathartics/purgatives and
laxatives with suitable examples.
☞ Cathartics (Purgatives):
The agents that promote defaecation are called cathartics.
The agents that facilitate the passage of and elimination of the faeces from the intestinal tract, especially through colon and rectum are called cathartics.
Cathartics are drastic purgatives.
Laxatives are mild purgatives.
Laxatives are the substances that loosen stools and increase
bowel movements.
According to the intensity of action cathartics are categorised
as:
Laxatives.
Purgatives.
Drastics.
Classification of cathartics/purgatives/laxatives: Cathartics
are classified as per mechanism of action:
Stimulant/irritant purgatives: Senna, phenolphthalein, castor oil.
Bulk purgatives: Methyl cellulose, sodium carboxymethyl cellulose.
Emollient purgatives: Liquid paraffin.
Saline cathartics: Magnesium sulphate, sodium potassium tartrate.
14 Write a note on “saline cathartics”/“saline purgatives”/ Osmotic laxatives.
☞ Saline Cathartics
Saline cathartics are the agents that quicken and increase evacuation from the bowels, e.g. magnesium sulphate, sodium potassium tartrate.
Mechanism of Action
Saline cathartics increase osmotic pressure thereby secreting additional fluid in intestinal tract.
This results in increase in bulk and stimulates peristalsis causing
evacuation from the bowel.
As saline cathartics increase the osmotic pressure and increase in peristalsis of GIT, they are used in the treatment of constipation.
Constipation
Constipation means hardening of stool which can be caused due to decreased peristaltic movements.
Constipation may be due to intestinal injury, change in food intake, change in food type, change in environment, lack of exercise and due to consumption of medicinal agents.
Thus, saline cathartics are mainly used in constipation.
Uses of Saline Cathartics
To treat constipation.
In hernia to avoid excessive straining.
In haemorrhoids, boils and rectal disorders.
To avoid rise in BP during defaecation.
To remove intestinal contents before X-ray examination.
15 Write a note on (a) magnesium sulphate, (b) sodium potassium tartrate.
☞ (a) Magnesium Sulphate
Formula: MgSO . 7 H O
4 2
Synonym: Epsom salt.
Preparations: It is prepared from magnesium carbonate and dil. H2SO4.
MgCO3 + H2SO4 → MgSO4 + CO2 + H2O
Properties
Colourless crystals with cool and saline taste.
It is soluble in water.
It shows phenomenon of efflorescence in dry air.
It is odourless, very soluble in boiling water.
Storage: It should be stored in well closed airtight containers in cool place.
Incompatibility: With alkali, carbonate and bicarbonates, NaI, potassium tartrate.
Uses
As a saline purgative.
In treatment of heavy metal poisoning as antidote.
It is used for wet dressing.
In the treatment of boils.
In hypertensive patients to avoid excessive straining (given as enema).
It is used parenterally as an anticonvulsant.
It is also used as cholegogue.
Because of its osmotic action, it has been used locally in
various inflammatory conditions.
It is a common ingredient of aperient mineral water.
Sodium Potassium Tartrate
Synonym: Rochelle’s salt, seignette salt.
Formula: C4H4KNaO6.4 H2O
Properties
It is colourless, odourless crystalline powder.
It has a cooling saline taste.
It is soluble in water and insoluble in alcohol.
It shows phenomenon of efflorescence.
Storage: Stored in tightly closed containers.
Incompatibility: With acids, calcium and lead salts.
Uses
As a cathartic, purgative.
As a stabilizer in cheese and meat products.
As ingredient of Fehling solution.
As ingredient of effervescent powders and bath soaps.
Agents
Topical Protective, Astringents,
1 What are topical agents? Classify them with examples.
☞ Topical Agents
The agents which are applied on the skin or mucus membrane for their local effects are called topical agents.
Classification
On the basis of chemical origin
Organic topical agents, e.g. zinc stearate, povidone iodine.
Inorganic topical agents, e.g. talc, zinc oxide, calamine.
On the basis of action of drugs
Protectives and adsorbents, e.g. talc, zinc oxide.
Antimicrobial agents, e.g. potassium permanganate, silver
nitrate.
Astringents, e.g. alum, zinc sulphate.
Miscellaneous compounds, e.g. sulphur and its derivatives.
Topical Protective
2 Write a note on “topical protectives”.
☞ Topical Protectives
The substances which are used to protect the skin from external environment and applied on skin are called topical protectives.
Examples: Talc, zinc oxide, calamine, titanium dioxide.
They are available in the form of dusting powder, lotions, lini-ment, creams, ointment, etc.
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Explanation
The substances having capacity to form a layer can protect the skin. These substances reduce mechanical friction, irritation, etc. These substances adsorb moisture and bacterial toxins and also protect skin from UV rays. These are insoluble in water and available in the form of powder. These are chemically and biologically inert and have good adsorption property, adequate flow property, sufficient covering capacity. These drugs are not adsorbed in circulatory system.
Applications
To protect skin from sun rays.
To protect skin from bacterial toxins, dust and dirt particles.
To protect skin from irritation and infections.
To protect ulcers and wounds from external hazards.
Astringents
3 Write a note on “astringents”.
☞ Astringents
The substances which have a capacity to precipitate superficial proteins are called astringents, e.g. alum, zinc sulphate.
Dosage forms: They are available in the form of dusting powders, mouthwashes, gargles, topical solutions, etc.
Explanation
Astringents are having less permeability and also very less penetration power. Therefore, when applied on skin, they are not affecting normal functioning of body cell.
Astringents show following types of actions (mechanism of action):
Styptic action: Astringents precipitate surface proteins and blood proteins present at the site of wound. Therefore, diameter of blood capillaries is reduced. Due to constriction of capillaries and small blood vessels they show styptic action, i.e. to stop bleeding from small cuts.
Anti-inflammatory action: Astringents reduce blood supply coming towards the tissue and histamine secretion is also decreased. Thus, anti-inflammatory action is obtained.
Antiperspirant action: Astringents precipitate surface proteins thus decrease the diameter of sweat and sebaceous glands. Thus, perspiration is reduced, i.e. antiperspirant action.
Antimicrobial action: Astringents precipitate cell proteins of microbial cell, therefore, malfunctioning of microbial cell occurs. Further, microbial cell cannot get multiplied and thus antimicrobial action is achieved.
Applications/Uses of Astringents
These are used as antimicrobial, anti-inflammatory, antiperspi-rants and styptic.
In the treatment of wounds, ulcers, etc.
In mouthwash and mouth freshener preparations.
In toothpaste and tooth powder preparations.
In dusting powders due to its antiperspirant action.
Antimicrobials
4 What are antimicrobial agents? Give the properties/ characteristics of an ideal antimicrobial agent. Mention the examples of antimicrobial agents.
☞ Antimicrobial Agents:
These are the chemical agents which are used to destroy or inhibit the growth of pathogenic microorganisms such as bacteria, fungi, protozoans.
☞ Terms used to describe antimicrobial activity:
Antiseptics: Antiseptics are the chemical agents which destroy or inhibit the growth of microorganisms when applied on living tissues.
Disinfectants: Disinfectants are the chemical agents which destroy or inhibit the growth of microorganisms when applied on non-living objects.
Bacteriostatic: The chemical agents that stop or inhibit the growth of bacteria are called bacteriostatic.
Bactericidal: The chemical agents that kill the bacteria, but not necessarily the bacterial spores are called bactericidals.
Germicide: It is a chemical agent that destroys pathogenic microorganisms/germs.
☞ Examples of various antimicrobial agents:
Oxidative antimicrobial agents, e.g. hydrogen peroxide solution, zinc peroxide, potassium permanganate, sodium hypochlorite solution, chlorinated lime.
Iodine preparations and compounds, e.g. iodine and iodine
solutions, povidone iodine.
Protein precipitant antimicrobial agents, e.g. silver nitrate, mild silver protein.
Mercury compounds, e.g. yellow mercurie oxide, ammoniated mercury, mercuric chloride.
Boric acid and borax.
☞ Characteristics/properties of an ideal antimicrobial agent:
It should have rapid onset of action.
It should have good therapeutic index.
It should have sufficient antimicrobial action.
It should be compatible with other ingredients.
It should be economical and should be required in very less
concentration.
It should not have any type of toxicity.
It should not damage host cell/tissue.
It should have sustained action.
It should have a broad spectrum action.
It should have an adequate “Lipid water distribution coeffi-cient.”
5 Explain the mechanism of action of inorganic antimicrobial agents.
☞ Antimicrobial agents may act by following mechanisms:
Oxidation
Halogenation
Precipitation
Oxidation: Antimicrobial substances convert sulfhydryl group to disulphide form. Therefore, disulphide group of proteins cannot work and thus kills microorganisms, e.g. hydrogen peroxide, KMnO4.
Halogenation: These substances add halogens to peptide linkage of microorganisms thus normal functioning of microbial cell gets disturbed, hence kills the microbes, e.g. iodine, povidone iodine, chlorinated lime.
Precipitation: Many antimicrobial agents containing metal ions react with polar group of proteins and form a complex thus there is inactivation of protein (precipitation of proteins) and antimicrobial action is achieved, e.g. boric acid, borax, silver nitrate, mercuric compounds.
6 Define and classify antimicrobial/Anti-infective agents with examples.
☞ Antimicrobial Agents:
The chemical agents which are used to destroy or inhibit the growth of pathogenic microorganisms such as bacteria, fungi, protozoans, are called as antimicrobials.
Classification of Antimicrobials as per use:
Antiseptics: The substances which have a capacity to kill microbes and prevent the growth of microbes when applied on living material, e.g. hydrogen peroxide.
Disinfectants: These are the substances having antimicrobial activity but used only for inanimate objects, e.g. cresol with soap solution.
Germicides: Agents which kill the germs.
Fungicide: Agents which kill the fungi.
Viricide: Agents which kill the viruses.
Bacteriostatic: Agents which stop the growth of bacteria.
Bacteriocidal: Agents that kill the bacteria.
Preservatives: These are the agents which prevent the contamination of products from microbes, e.g. methyl paraben.
Classification of Antimicrobial Agents on Chemical Basis:
Acids: Boric acid, salicylic acid.
Aldehyde and alcohols: Ethanol, formaldehyde, glutaralde-hyde, isopropanol.
Halogens and its derivatives: Chlorinated lime, chlorhexidine, iodine, iodopovidone, povidone iodine, sodium hypochlorite.
Metallic salts: Copper sulphate, silver nitrate, zinc sulphate.
Oxidizing agents: Hydrogen peroxide, potassium permanganate.
Phenol derivatives: Cresol, phenol, resorcinol.
7 Give the formula, synonym, properties, storage, incompatibility, and uses of following antimicrobial agents: (a) Silver Nitrate (b) Hydrogen Peroxide,
(c) Boric Acid, (d) Bleaching powder (chlorinated lime), (e) Potassium permanganate, (f) Ionic silver,
(g) Chlorhexidine Gluconate.
☞ (a) Silver Nitrate (protein precipitant antimicrobial agent) :
Chemical formula: AgNO3.
Standard: It contains not less than 99.8% w/w of AgNO3 when powdered and dried in the dark over sulphuric acid fumes for four hours.
Properties:
It is a colourless or white crystalline, odourless compound with bitter metallic taste.
It becomes grey or greyish black on exposure to light in the presence of organic matter due to liberated silver.
It is very soluble in water, sparingly soluble in alcohol but freely soluble in boiling alcohol.
A 1% solution in water has pH between 4.5 and 6.0.
At higher temperature it slowly decomposes, evolving oxides of nitrogen.
Method of preparation:
It is prepared by the action of hot nearly concentrated nitric
acid for four hours.
Ag + HNO3 → AgNO3 + NO2 ↑ + H2O
Chemical reactions:
It melts at 208°C and gives a yellowish liquid without decomposition. On heating to red heat it decomposes with evolution of NO2 and O2, leaving a residue of metallic silver.
2 AgNO3
D
(Red hot)
2 Ag + 2 NO2
↑ + O2
3
With hydrochloric acid or soluble chlorides it gives a white curdy precipitate of silver chloride.
AgNO3
+ HCl HNO3 AgCl ↓ + HNO
HNO3
3
AgNO3 + NaCl AgCl ↓ + NaNO
Sodium carbonate on addition to silver nitrate solution precipitates silver carbonate which on heating gives silver oxide.
2 AgNO3 + Na2CO3 → Ag2CO3 + 2 NaNO3
Ag CO D Ag O + CO ↑
2 3 2 2
Silver nitrate precipitates protein and form silver protein compound, which is the basis for the direct antimicrobial action of silver compound.
Storage: It should be stored in air tight amber coloured glass bottles in cool and dark place. Solution should be stored in alkali free bottles.
Incompatibility: It is incompatible with tartaric acid, hy-drocyanic acid, alkalies, halogen acids and their salts, phosphates, tannins and astringent preparations.
Uses:
It is primarily used as protein precipitant antimicrobial
agent.
It is used for its caustic astringent and antibacterial properties.
It has been used as a caustic to destroy warts and other
small skin growths.
A 1% solution has been used as a paint in the treatment of
pruritus ani (itching in anal region).
Gauze soaked in a 0.5% of silver nitrate is applied to severe burns to reduce infection.
Its aqueous solution (0.2 to 0.6%) is used as eye lotions.
Dilute solutions have been used as mouthwashes to help quit smoking.
Ammonical silver nitrate is used in dentistry as a protective of dentin.
Hydrogen peroxide:
Chemical formula: H2O2.
Synonym: Oxygenated water, oxydol, perhydrol.
Properties:
Hydrogen peroxide solution is a colourless liquid.
It is odourless liquid with slightly acidic taste.
Its specific gravity is 1.463 at 0°C.
It is soluble in water, alcohol and ether.
It can be extracted with solvent ether from its aqueous
solution.
Method of preparation:
Hydrogen peroxide is prepared by the action of sulphuric acid on hydrated barium peroxide.
BaO2 + H2SO4 → BaSO4 + H2O2
Incompatibility: With reducing agents, oxidising agents, or-
ganic matter, heavy metals.
Stability storage: It should be stored in light resistant containers with stoppers resistant to hydrogen peroxide. It should be stored in cool place.
Label: The label should state whether or not the solution contains a stabilising agent.
Uses of H2O2:
It is a mild oxidising antiseptic. It destroys most pathogenic bacteria.
Solution of hydrogen peroxide (6%) is used as disinfectant.
It is used for its cleansing action on cuts and wounds.
It is also used to cleanse septic sockets and root canals of teeth.
It is used for loosening of ear wax and also for the removal of sticking surgical dressings from the wounds.
A 1.5% solution of hydrogen peroxide is used as a deodorant, gargle and mouthwash.
Hydrogen peroxide is used as an antidote in phosphorus and cyanide poisoning.
It is used for bleaching the hair.
It is used as antimicrobial agent and topical anti-infective
agent.
Boric Acid:
Chemical formula: H3BO3.
Synonym: Boracic acid, orthoboric acid, acidum boricum.
Standard: It contains not less than 99.5% of H3BO3.
Method of preparation:
It is prepared by boiling the solution of native borates with
sulphuric acid.
Na2B4O7 + H2SO4 + 5 H2O → Na2SO4 + 4 H3BO3
Properties:
It is a white, odourless powder with bitter taste.
It is soapy to touch.
Soluble in hot water and freely soluble in glycerine.
Solution is isotonic with body fluids.
Storage: It should be stored in well closed container. Label
should indicate:
“It should not be taken internally.”
“It should not be applied on broken skin.”
Incompatibility: It is incompatible with tannins, benzalkoni-um chloride and polyvinyl alcohol.
Uses of Boric Acid:
Boric acid has a weak bacteriostatic and fungistatic action.
It is mild antiseptic.
Externally it is used for irrigation of organs.
It is used in dusting powders.
It is an ingradient of mouthwash and eye wash.
It is used as a buffer in ophthalmic preparations.
It is used to reduce inflammation of various skin disorders.
Boric acid is used to impregnate a number of surgical dressings.
Bleaching powder (Chlorinated Lime, Chloride of Lime)
Chemical formula: CaOCl(Cl), H2O.
Synonym: Chlorinated lime, chloride of lime.
Standard: It contains not less than 30% w/w of a available
chlorine.
Method of preparation:
It is prepared by the action of chlorine on calcium hydroxide,
i.e. on slaked lime which must be pure and fairly dry. Ca(OH2) + Cl2 → Ca(OCl)Cl + H2O
Properties:
It is a dull white powder with odour of chloride.
It is slightly soluble in water and less soluble in alcohol.
On exposure to air, it becomes moist and forms chlorine
gas.
Storage: It should be stored in air tight containers in a cool place protected from light.
Uses:
It is used as disinfectant and bleaching agent.
It has bactericidal action.
It is used to disinfect faces, urine, sputum, etc.
It is used for disinfecting drainages.
It is used for sterilisation of water.
It is used in the preparation of surgical chlorinated soda solution used as a wound disinfectant.
Potassium permanganate:
Chemical formula: KMnO4.
Synonym: Condy’s crystals.
Standard: It contains not less than 99% of KMnO4 as per I.P.
Method of preparation:
Manganese dioxide is fused with excess of potassium hydroxide in the presence of free supply of air or with the addition of some suitable oxidizing agent such as potassium nitrate or potassium chlorate, potassium permanganate is formed.
2 KOH + MnO2 + [O] → K2MnO4 + H2O
Properties
It is an odourless dark purple-coloured crystalline compound.
It has greenish-blue metallic lustre.
It has sweet astringent taste.
It is soluble in water.
Its concentrated solutions are deep voilet.
When mixed with glycerin, it burns.
Incompatibility: With iodides, reducing agents and organic
substances.
Storage: It should be stored in tightly closed container and avoid contact of organic matter. It should be handled with care.
Uses
As antimicrobial agent.
Powerful cleansing agent for wounds, ulcers.
In mouthwash and gargles.
As a deodorant.
Antidote in barbiturate poisoning.
For gastric lavage treatment.
It leaves the stains on skin or tissues.
Ionic silver:
Ionic silver is the silver ions stabilized with other reagent or
compounds.
Ionic silver is produced using electrolysis with water, some wire and a battery.
Many products being sold as a colloidal silver are actually ionic silver.
For many years, ionic silver has been used as the “Ultimate” antibiotic, antifungal and antiviral treatment.
Dietary silver does not have a daily requirement because it is not
considered as an essential mineral.
According to studies the average person consumes between 23
and 88 mg of silver every days.
Uses:
It is used in:
Eye and ear infections.
In blocked sinuses.
Cold and flu.
Respiratory problems.
Eczema, psoriasis.
Skin problems.
Cuts and burns.
Chlorhexidine gluconate:
Formula: C34 H54Cl2N10O14.
Synonym: Chlorhexidine digluconate.
Description:
Chlorhexidine gluconate is used as an antiseptic agent with topical antibacterial activity.
Chlorhexidine gluconate is a germicidal mouthwash that
reduces bacterial growth in mouth.
Chlorhexidine gluconate oral rinse is used to treat gingivitis (swelling, redness, bleeding gums)
It is usually prescribed by a dentist.
Uses:
It is found in disinfectants, cosmetics.
In pharmaceuticals.
In dentistry and as antiseptic.
As a germicidal mouthwash.
As a oral rinse to treat gingivitis (swelling, redness,
bleeding gums).
Products
1 Write a note on dental products. Or Discuss various types of inorganic compounds used in dentistry and in dental products.
Dental caries (tooth decay) is a disease of teeth which gives decalcification of tooth and bad odour of the mouth.
To prevent dental caries and to maintain clean and healthy teeth, it is necessary to use dentifrices.
Dentifrices may be toothpaste or tooth powder are used to clean dirty surface of teeth.
Dental products are used in dentistry.
Dental products are available in several dosage forms as toothpaste, tooth powders, silver polishes, oils, etc.
Dental products contain:
Anticaries agents: The agents which are used in the treatment of dental caries are called anticaries agents, e.g. sodium fluoride, stannous fluoride.
Cleansing agents/abrasives: These are the substances used to remove stain from the teeth, e.g. calcium phosphate, di-calcium phosphate, sodium phosphate.
Polishing agents: The substances which give whiteness to teeth by their abrasive action are called polishing agents,
e.g. stannous fluoride, calcium carbonate.
Desensitizing agents: The substances which reduce the sensitivity of teeth to heat and cold are known as desensitizing agents, e.g. zinc chloride, strontium chloride.
Sweetening agent: It gives sweet taste.
Colouring agent: It gives attractive colour to the preparation.
Flavouring agent: It provides pleasant flavour.
95
Humectant: It prevents drying of toothpaste preparation,
e.g. glycerin.
2 Discuss the role of fluorides as anticaries. What is dental fluorosis?
☞ Anticaries
The substances which can prevent the formation of cavities in teeth are called anticaries agents.
Anticaries agents are fluorides, phosphates and ammoniated compounds.
Role of Fluorides
Role of fluorides in preventing dental caries is well accepted.
Administration of small quantity of fluorides in dental product may produce good results.
Fluorides act as anticaries by two mechanisms:
Fluorides decrease the solubility of enamel in lactic acid and also act against bacterial growth.
Lactic acid is formed during the partial digestion of carbohydrates. This acid has ability to dissolve the enamel. Therefore, bacteria can localise on surface of teeth and thus cavities can be formed.
Fluorides act by inhibiting bacterial growth.
Fluorides are having toxicity when they are taken in large quantity.
When more quantity of fluoride is ingested, it is carried to bones and teeth and produces mottled enamel which is known as dental fluorosis.
Fluorides are carcinogenic when deposited on teeth.
When a fluoride-containing solution is taken (orally) internally it gets readily absorbed, transported and deposited in the bone or teeth and remainder is excreted by the kidneys.
The deposited fluoride on the surface of teeth prevents the action of acids.
3 Give the formula, synonym, properties storage, uses, incompatibility of following inorganic compounds used in dental products. (a) Sodium fluoride, (b) Calcium carbonate.
☞ (a) Sodium fluoride:
Formula: NaF
Preparation: It is prepared by evaporating a solution of stannous oxide, in hydrofluoric acid in the absence of oxygen.
Properties:
It occurs as a white, odourless powder with slight bitter taste.
It is freely soluble in water and practically insoluble in alcohol, ether and chloroform.
Storage: It is stored air tight containers to avoid hydrolysis and oxidation.
Incompatibility: It is incompatible with magnesium and calcium salts. Aqueous solution of sodium fluoride attacks glass slowly.
Uses:
Sodium fluoride is used for the prophylaxis of dental caries (anticaries agent)
It is used in dental products.
A 2% solution of sodium fluoride in water may be applied to children’s teeth.
It is used to treat abnormal development of teeth.
It is a constituent of some insecticides and rodenticides.
(b) Calcium carbonate:
Formula: CaCO3.
Synonym: Precipitated chalk, precipitated calcium carbonate.
Standard: It contains not less than 98.5% of CaCO3.
Description:
Calcium carbonate is the most abundant and widely distributed calcium salt.
It occurs as a chalk, lime stone, marble, aragonite and calcite.
Method of preparation:
Calcium carbonate is prepared by precipitation by mixing the boiling solution of calcium chloride and sodium carbonate and allowing the resulting precipitate to subside on cooling.
CaCl2 + Na2CO3 → 2 NaCl + CaCO3 ↓
Properties:
It is white odourless, tasteless, microcrystalline powder stable in air.
It is practically insoluble in water, but its solubility is increased by the presence of any ammonium salt or carbon dioxide.
Storage: It is stored in well closed air-tight containers.
Incompatibility: It is incompatible with tetracycline. Administration of large dose of calcium carbonate with large amount of milk can cause milk-alkali syndrome (Brunette syndrome).
Uses:
Calcium carbonate is used as a dental cleaning-polishing agent for most of toothpastes and tooth powders.
It is used as an antacid.
It is used as a chalk and also in the treatment of diarrhoea.
A preparation of native calcium carbonate is used in hameo-pathic medicine.
4 Write a note on: (a) Mouthwashes, (b) Denture cleaners.
(c) Denture adhesives
☞ (a) Mouthwashes:
A mouthwash is an aqueous solution like a gargle but used to wash the mouth cavity.
Explanation
Mouthwashes are used for their deodorant refreshing or antiseptic effects.
They may contain alcohol, glycerin, surfactants, sweeteners, flavouring and colouring agents.
Generally mouthwash contains:
Antibacterial agent: Phenol, hydrogen peroxide.
Astringent: Zinc chloride, zinc sulphate.
Simple preparation: Sodium chloride solution.
Flavours.
Humectants.
Buffers.
Label
For external use only.
Dilute with equal volume or specified volume of warm water before use.
Container
Mouthwashes should be dispensed in a clear flutted glass bottles, closed with a plastic screw cap.
Examples
Alkaline phenol mouthwash BPC.
Hydrogen peroxide mouthwash BPC.
Compound sodium chloride mouthwash BPC.
Zinc sulphate and zinc chloride mouthwash BPC.
Denture cleaners:
Denture is a removable replacement for missing teeth and surrounding tissues.
Conventional dentures are removable.
When dentures are removed from the mouth, a denture cleaner (denture cleanser) is used to clean them.
The main purpose of denture cleaner is to prevent denture related stomatitis by controlling the growth of bacteria on the dentures, particularly Candia albicans.
When dentures are worn in the mouth, a biofilm forms that looks and feels like dental plaque. It can solidify and mineralize, forming dental calculus.
Denture cleaners are also used to remove stains, and other debris generated by a variety of factors such as diet, tobacco usage, coffee, tea and other beverages.
Chemical denture cleaners are available in both cream and liquid form. They may be effervescent or non-effervescent.
Dental brushes and ultrasonic denture cleaners are mechanical denture cleaners that use ultrasonic cleaning, some of which are combined with UV radiation.
Formula for Denture cleaner:
Dilute sodium hypochlorite (a weak bleach) (principle ingredient)
Sodium bicarbonate (baking soda): It is an alkalizing agent that cleans denture by alkalinizing the water.
Citric acid: It removes spots.
Potassium monopersulphate: It is used as cleaning and bleaching agent.
Sodium perborate, sodium polyphosphate, and EDTA.
Uses of Denture cleaners:
To prevent growth of bacteria on dentures.
To remove stains and spots on the dentures.
To remove the dental plaque/calculus.
Denture Adhesives:
Definition: Denture adhesive is a paste, powder or strip made from a non-toxic water-soluble material that goes between the denture and the gum line.
Types of Denture Adhesives:
Denture adhesive cream.
Denture adhesive powder.
Denture adhesive strips.
Composition of Denture Adhesive:
The composition of denture adhesives is as following:
Zinc: This mineral helps the adhesive create that grip you need.
Mineral oil: This ingredient delivers the right denture cream consistency.
Petrolatum: Like mineral oil, this helps with consistency.
Cellulose gum: This ingredient helps the dentures stick in place.
Silica: Also works to help create the right consistency.
Red 27 Lake: This ingredient gives the adhesive its color.
Mechanism of Denture Adhesives:
Denture adhesives work by “gluing” (fost joining) the denture to the tissue through the saliva.
Mouth’s natural moisture transforms the adhesive into an elastic like membrane that sticks to both the gum and the denture.
Denture adhesives hold dentures tight and improve natural retention after well fitting denture.
Uses of Denture Adhesives
Denture adhesives help to enhance the natural forces that hold denture in place and help to stop any movement between the denture and the gum, so that person can eat, talk, smile and live with more confidence.
Denture adhesives can also help to give more confidence since dentures are held firmly in proper place.
(Inhalants)
1 Define inhalants. What is the role of oxygen and carbon dioxide in biological system?
☞ Inhalants
The substances which are in vapour or gas form are inhaled through nose, are called inhalants, e.g. O2, N2O, CO2.
Role of Oxygen (O2)
Oxygen is necessary in normal oxidative metabolism for the production of useful energy.
This energy is used by the cell to synthesize ATP.
After inhalation, O2 enters into blood and combines with
haemoglobin to form oxyhaemoglobin (HbO2).
This oxyhaemoglobin readily dissociates and releases oxygen in
the medium of cell.
Deficiency of oxygen in tissues is called hypoxia.
Absence of oxygen in the tissues is called anoxia.
When more oxygen is needed the condition is termed as asphyxia.
For the treatment of hypoxia, anoxia and asphyxia, O2 is needed.
In the treatment of poisoning, O2 is useful for maintenance of
normal respiratory and circulatory functions.
Role of Carbon Dioxide (CO2)
CO2 plays an important role in maintaining acid–base balance of the body.
It is found in large quantity in plasma.
It is readily absorbed and transported by blood both in cells and in plasma. It is also produced in the body during metabolic process.
101
Carbonate buffer is physiological buffer which is useful in maintenance of acid–base balance of several body fluids.
A large quantity of carbon dioxide produced is eliminated by lungs in expired air.
Respiratory acidosis and respiratory alkalosis are the disorders
produced due to imbalance of CO2 level in the body.
CO2 stimulates respiratory centre and hence useful in treatment of carbon monoxide poisoning.
2 Write a note on “oxygen” as a Medicinal gas.
☞ Oxygen
Formula: O2
Standard: Oxygen contains not less than 99% w/v of O2.
Preparations: By two methods:
By electrolysis of water.
By fractionation of liquid air.
Properties:
Colourless, odourless, tasteless gas.
It is a good oxidising agent.
It dissolves in about 32 volumes of water.
Storage and labelling
It is stored under the pressure in metallic cylinder which is painted by black and white colour. The body of the cylinder is painted by black and shoulder is painted with white colour.
Name and symbol of oxygen (O2) is stenciled on cylinder and also on cylinder valve.
Actions and uses
In treatments of hypoxia, anoxia and asphyxia.
In carbon monoxide poisoning.
In cardiac arrest.
As a fuel in rocket technology.
In the preparation of acetylene flame used for welding.
Medicinal Gases (Inhalants) 103
3 Write a note on “carbon dioxide” as a medicinal gas.
☞ Carbon Dioxide
Formula: CO2
Standard: It contains not less than 99% w/v of CO2.
Preparation: Compounds containing carbon, e.g. coal, coke are burned in excess of O2 to produce CO2.
C + O2 → CO2
Properties
Colourless, odourless gas with faintly acidic taste.
Soluble in water and heavier than air.
Storage and labelling
It should be stored under pressure in a strong metallic cylinder.
The cylinder is painted grey colour at shoulder and remaining part may be of green or white colour.
Actions and uses
Respiratory stimulant.
In carbon monoxide poisoning.
In treatment of drug addiction.
Regulation of acid–base balance.
Its salts are used in effervescent powders.
In preparation of soft drinks.
To prepare dry ice.
With O2 for artificial respiration.
4 Write a note on “nitrous oxide” as a medicinal gas.
☞ Nitrous Oxide
Synonym: ‘Laughing gas’, Happy gas, Nitrous monoxide.
Formula: N2O
Standard: It contains not less than 99% w/v of N2O.
Preparation: It is prepared by thermal decomposition of ammonium nitrate.
NH4NO3 → 2 H2O + N2O
Properties
It is colourless, odourless gas with slightly sweet taste.
It is soluble in water and alcohol.
Storage and labelling
It should be stored under pressure in a strong metallic cylinder below 37°C.
The cylinder is painted by blue colour.
The name and symbol of nitrous oxide (N2O) are stenciled
on cylinder and on the cylinder valve.
Actions and uses
In minor operations of boils (as anaesthetic).
In dentistry.
In mental patients (to calm).
It produces nervous excitement and hysterical laughter, hence it is known as laughing gas.
It is also used as propellant in aerosol pack.
It also produces muscle relaxation.
Chemistry
System
and Nomenclature
1 Define the terms carbocyclic compounds and heterocyclic compounds.
☞ 1. Carbocyclic Compounds
The cyclic compounds containing all the carbon atoms along with hydrogen atoms are called carbocyclic compounds.
Examples
Benzene Cyclopropane
H2C
CH2
CH2
Heterocyclic Compounds
The cyclic compounds containing one or two different kinds of atoms (hetero atoms like, N, S, O) including carbon atoms are called heterocyclic compounds.
Examples
Pyridine Furan Pyrrole
O N H
2 Classify organic compounds giving suitable examples.
On the basis of carbon skeleton, organic compounds are classified
as follows:
106
3 Give the rules for numbering of the heterocycles/rings. Or Write a note on nomenclature of the heterocyclic rings.
Numbering of the heterocyclic systems can be done as per the following rules:
If the two heterocyclic rings contain only one hetero atom (N, S, O) then first number is given to hetero atom and other atoms are numbered either in clockwise or anticlockwise direction, e.g. pyridine
4 4
5 3 3 5
or
6 2 2 6
N1 N 1
If the heterocyclic ring contains two or more nitrogen atoms, then the saturated nitrogen should be numbered as 1 and other nitrogen atom should be given least possible number, e.g. pyrazole
4
3
5
N2
3 4
N
5
N
or 2 N
1 1
H H
If the heterocyclic ring contains two or more saturated nitrogen atoms then any one nitrogen is numbered as 1 and other nitrogen should come to least possible number, e.g. pyrazolidine
4 3
5 N H or
N1 2
H
4 5
3 N H
N2 1
H
If the heterocyclic ring contains two different hetero atoms, then
108 Pharmaceutical Chemistry
the order of preference for position 1 is oxygen, sulphur and then nitrogen and other hetero atoms are given lowest possible numbers, e.g. oxazole and thiazole
4 N 3
3 N 4
5 2
O
1
Oxazole
2 5
S
1
Thiazole
If heterocyclic ring having one of the substituents then it should
bear least possible number, e.g. nicotinic acid
4 COOH
5 3
6 2
N 1
H
4
Give the numbering and one example of each of the following heterocycles.
5 Give the structure/composition of the following organic groups/functional groups.
Organic groups Structure/composition
Methyl
Ethyl
n-Propyl
n-Butyl
Iso-propyl
Oxy/oxo
Methoxy
Ethoxy
Propoxy
Butoxy
Amino
Methyl amino
Ethyl amino
Propyl amino
Isopropyl amino
Diethyl amino
Dimethyl amino
Phenyl
Benzyl
Contd.
Organic groups Structure/composition
20. Phenoxy
Anilino
Guanidino
Biguanidino
Acetyl
Acetoxy
Acetamido
Phenyl acetamido
Phenoxy acetamido
Carbonyl
Carbamoyl
Carbamoyloxy
Benzoyl
Benzoyloxy
Thio
Cyano/nitrile
Hydroxy
Contd.
Organic groups Structure/composition
Carboxy/carboxyl
Formyl/aldehyde
Mercapto
Chloro
Bromo
Fluoro
Iodo
Hydroxymethyl
Hydroxyethyl
Nitro
2-Phenylethyl
2-Phenoxyethyl
Trifluoromethyl
Furfuryl
Vinyl
Vinyloxy
Allyl
Allyloxy
Sulphamoyl/sulphonamid
Sulphanilamid
Anaesthetics
1 What is Anaesthesia? Describe various stages of general anaesthesia / Explain mechanism of action of general anaesthetics.
☞ Anaesthesia
Anaesthesia is a state of controlled, temporary loss of sensation, that is induced for medical purposes. Anaesthesia includes stages like analgesia, paralysis, amnesia and unconsciousness.
☞ Stages of Anaesthesia/Mechanism of Anaesthesia
Stage of Analgesia: This stage from begining of inhalation of anaesthetics agent up to loss of consciousness. It involves sensation of falling, remoteness and feeling of warmth is observed in some patients. Analgesia is produced before consciousness is lost.
Stage of Delirium: This stage starts with loss of consciousness to beginning of surgical anaesthesia. This stage involves marked excitement, shouting, laughing, increased muscular activity, vomiting, pupils may dilate and patient shows development of marked hypertension and tachycardia.
Stage of Surgical Anaesthesia: As the more drug gets in, deep breathing starts and patient passes into the third stage. This gives gradual loss of reflexes, regular respiration and relaxation of skeletal muscle.
This stage is divided into four different planes :
Plane 1: The pupils are normal and eyeballs are moving. The pupils dilate and attain normal size. The respiration is full and regular. BP and pulse rate is normal.
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Plane 2: Eyeballs are fixed and amplitude of respiration is diminished. Adequate muscular relaxation.
Plane 3: The BP begins to fall. Intercostal muscles are paralysed slowly. The pupillary light reflex is lost. Muscles relax completely.
Plane 4: Intercostal muscles completely paralysed. The pupils are further dilated. BP is low. All secretions are completely abolished.
Stage of Respiratory Paralysis: This stage is characterised by severe depression of vital medullary centres, initially the diaphragmatic contractions are irregular. Respiratory arrest also leads to vasomotor collapse.
2 Define and classify general anaesthetics with examples.
General anaesthetics are the CNS depressant drugs, which produce a partial or total loss of pain accompanied by loss of consciousness.
☞ Classification
3 Differentiate between General Anaesthetics and Local
Anaesthetics.
General Anaesthetics
Local Anaesthetics
General anaesthetics are the agents which bring about loss of all modalities of sensation, particularly pain, along with a reversible loss of consciousness.
General anaesthesia is induced either by inhalation of volatile and gaseous anaesthetics like diethyl ether, halothane or parenteral administration of intravenous anaesthetics like thiopentone.
General anaesthesia is carried out before carrying out surgical operation or in obstetrics.
Care of vital organs is essential.
In this case consciousness is lost.
In this case site of action is on CNS.
Examples: Ether, halothane, cyclopropane.
It may be defined as any substance applied topically or by localized injection or infiltration to dull or block pain sensation.
Local anaesthesia is induced by topical application of drug to skin or mucous membrane or by injection into area subjected to surgical operation or injection into dural membrane of spinal cord.
Local anaesthesia is produced in short surgical operations and in dentistry.
Care of vital organ is not essential.
In this case effect is in limited area of the body.
In this case site of action is on peripheral nerves.
Examples: Lignocaine, procaine, orthocaine.
4 Give the structure, chemical Name, properties, storage, uses, official preparation of Brand names of the following general anaesthetics:
1. Thiopentone sodium, 2. Ketamine and 3. Propofol.
☞ 1. Thiopentone sodium/Thiopental sodium:
☞ Structure:
☞ Chemical Name:
Sodium, 5-ethyl-4, 6-dioxo-5-pentan-2yl 1H-pyrimidine-2-thiolate.
OR
5-ethyl-5 (1-methyl butyl)-2-thiobarbiturate sodium.
Properties:
It is yellowish white powder.
It has characteristic odour and has bitter taste.
It is freely soluble in water and practically insoluble in ether.
It is hygroscopic.
Stability and Storage:
It is hygroscopic and is decomposed by atmospheric O2. Hence, it is stored in tightly closed containers.
Uses:
It is used:
To induce general anaesthesia.
As an anticonvulsant.
For prevention and treatment of cerebral ischaemia.
It has poor analgesic and muscle relaxant property.
It is also used as sedative and hypnotic.
☞ Phamaceutical Formulations:
Thiopentone sodium injection IP, BP.
Brand Names:
Pentothal Sodium, Intraval Sodium, Thipen, Thiosol, Anesthal.
Ketamine:
☞ Structure:
☞ Chemical Name:
2-(2-chlorophenyl)-2-(methyl amino) cyclohexane-1-one, hydrochloride.
OR
2-(2-chlorophenyl)-2-(methyl amino) cyclopentanone hydrocloride.
Properties:
It is a white or white crystalline powder.
It is freely soluble in water, methanol and ethanol.
Stability and Storage:
Ketamine solutions were chemically stable for periods ranging from 7 to 180 days when stored at 4°C or 25°C in plastic or glass containers.
Uses:
It is a dissociative anaesthetic.
Ketamine induces sedation, immobility, amnesia and marked analgesia.
It is a rapidly acting non-barbiturate general anaesthetic.
Ketamine is a phencyclidine analogue with anaesthetic and analgesic properties.
Ketamine is a anaesthetic agent used for diagnostic and surgical procedures.
Ketamine produces an anaesthetic state characterized by profound analgesia.
☞ Phamaceutical Formulations: Ketamine injection
Brand Names:
Ketalar, GB-ket, Keta, Hypnoket, Aneket.
Propofol:
Structure:
Chemical Name:
2,6.-di-isopropyl phenol
Properties:
It is lightly straw coloured liquid.
It is insoluble in water and soluble in alcohol and toluene.
Storage:
It undergoes oxidative degradation in the presence of oxygen and therefore packaged under nitrogen to eliminate this degradation path. It is stored in the temperature ranging between 4°C and 25°C.
Uses:
It is used as parenteral anaesthetic agent.
It is used in intensive care units (ICUs) for maintenance of coma.
It induces the sedation and hypnosis during anaesthesia.
It is used for general anaesthesia in major surgery.
In low doses it is also used for “conscious sedation” of patients getting procedures on an outpatient basis at ambulatory surgery centres.
☞ Pharmaceutical Formulations: Propofol injection
Brand Names:
Profol, Neorot, Celofol, Diprivan, Hypro.
Hypnotics
1 What is Insomnia ? Define and classify sedatives and hypnotics with examples:
☞ Insomnia
Insomnia means lack of sleep or inability to sleep.
Classification of Sedatives and Hypnotics
Barbiturates:
Long acting: Barbital, phenobarbitone, mephobarbital.
Short acting: Amobarbital, butabarbital, pentobarbital, seco-barbital.
Ultrashort acting: Thiopentone, methohexitone.
Benzodiazepines: Diazepam, chlordiazepoxide, oxazepam, chlorazepate, lorazepam, alprazolam, zolpidem.
Miscellaneous:
Amides and imide: Glutethimide.
Alcohols and their derivatives: Meprobamate, ethchlorvynol.
Aldehydes and their derivatives: Triclofos sodium, paralde-hyde.
Acetylated carbinols: For example, ethionamate.
Inorganic ions: For example, bromides.
2 Give the details of following sedative and hypnotic drugs.
☞ 1. PHENOBARBITONE
It is a derivative of barbituric acid.
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Structure:
Properties
It is a white crystalline powder.
It is odourless and has slightly bitter taste.
It is very slightly soluble in water and soluble in alcohol.
It is hygroscopic.
It is lipophillic in nature thus soluble in benzene and acetone.
Stability and Storage
It is hygroscopic in nature, hence it is stored in tightly closed container.
Uses
It is used as a hypnotic and sedative.
It is used to treat insomnia, anxiety, dysmenorrhoea and thyrotoxicosis.
It is used to treat neonatal jaundice.
It is used as antiepileptic for grand mal and petit mal epilepsy.
☞ Pharmaceutical Formulations:
Phenobarbitone tablet.
Phenobarbitone and theobromine tablet.
Phenobarbitone capsules.
Phenobarbitone elixir.
Phenobarbitone sodium tablets.
Phenobarbitone sodium injection.
Brand Names
Garoin, Garnenal, Luminal, Fenobarb, Phenetone, Epitan, Beetal.
DIAZEPAM
It is a benzodiazepine derivative.
Structure:
Chemical Name:
chloro, 2,3-dihydro, 1-methyl, 1-4 benzodiazepine, 2-one
Properties
It occurs as white or pale yellow crystalline powder.
It is odourless and tasteless.
It is sparingly soluble in water and soluble in alcohol.
It is lipophillic in nature, thus soluble in benzene and acetone.
Stability and Storage
It should be stored in a tightly closed light resistant container.
Therapeutic Uses
It is used as antianxiety agent.
It has a good muscular relaxation property.
It is used as an anticonvulsant agent.
It is used as preanaesthetic medication.
It is used in the management of acute alcoholic withdrawal.
It is used as hypnotic and sedative.
☞ Pharmaceutical Formulations:
Diazepam tablet.
Diazepam capsule.
Diazepam injection.
Diazepam elixir.
Diazepam oral solution.
Brand Names:
Calmpose, Valium, Diazep, Alzepam, Calmod, Dizac, Q-pam.
Dose:
The standard dosage in 2 to 10 mg two to four times per day.
ALPROZOLAM
It is a benzodiazepine derivative.
Structure:
Chemical Name:
chloro, 1-methyl-6-phenyl-4 H-1, 2, 4-triazolo [4, 3a] [1, 4] benzodiazepine.
Properties:
It is a white crystalline odourless solid powder.
It is practically insoluble in water, freely soluble in methylene
chloride, sparingly soluble in acetone and alcohol.
Stability and Storage:
It should be stored in a tightly closed container in a dry and well-ventilated place. It should be stored in light resistant container at 15–30°C.
☞ Pharmaceutical Formulations:
Alprazolam tablet.
Alprazolam injection.
Brand Names:
Xanax, Aaram, Abirox, Niravam, Agcalm.
Uses:
It is useful in the short-term management of insomnia.
It is used as sedative and hypnotic.
It is used as an antianxiety agent.
It is used in panic disorders (sudden unexpected attacks of
extreme fear and worry about these attacks)
NITRAZEPAM
It is a benzodiazepine derivative.
Properties:
It is a yellow, crystalline and odourless powder.
It is soluble in alcohol, acetone, chloroform and ethyl acetate.
It is insoluble in water, ether, benzene and hexane.
Stability and Storage:
It should be stored at room temperature and protected from light and moisture.
☞ Pharmaceutical Formulations:
Nitrazepam tablet.
Nitrazepam injection.
Brand Names:
Nitravet, Insomine forte, Hypnotex, Nitrosun, Nitraz-5.
Antipsychotics
(Tranquilizers/Neuroleptics)
1 What are different Psychic disorders/Psychological disorders/mental disorders?
☞ Types of Psychic/Mental disorders:
Psychosis: It means a mental condition characterised by disturbances in mental functions.
It is a psychic condition, which involves marked impairment of behaviour with a serious inability to think.
Mental diseases have always been puzzling and frightening things.
Psychosis can be defined as the psychotic illness with serious distortion of thought, behaviour and capacity to recognize reality and of perception and patient unable to meet the ordinary demand of life.
Psychoses may be of two categories:
Organic Psychosis: It involves memory disturbances, clouding of consciousness, congestive disorders, like delirium, and dementia with psychotic features.
Prominent features are confusion, disorientation, defective memory, disorganized thoughts and behaviour. They may be due to endocrinal abnormalities or head injuries.
Functional Psychosis:
Maniac: Disturbance of mood, reduced sleep, hyperactivity, uncontrollable thoughts and speech, violent behaviour.
Schizophrenia: It is also known as split mind condition. It involves splitting of perception and interpretation from reality and inability to think. Disturbed emotions and motor behaviour.
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Hallucination: A sensation of false perception without
sensory stimulus.
Anxiety: It involves feeling of fear, apprehension.
Neurosis: It is a termed used to denote less severe form of psychosis.
Depression: It is a common psychiatric disorder characterized by a feeling of misery, apathy, hopelessness, ugliness, loss of appetite, insomnia, anorexia, alternation in moods and activities, etc.
2 Define the terms with examples:
☞ Definitions:
Antipsychotics/Psychotropics/Psychoactive Drugs
The drugs which are used in the treatment of psychic disorders are called antipsychotics or psychoactive drugs. For example, chlorpromazine, reserpine, haloperidol.
Antianxiety Agents/Anxiolytics/Minor Tranquillizers
The drugs which are used to reduce anxiety states and nervousness are called antianxiety agents. For example, diazepam, nitrazepam, oxazepam.
Antidepressants (Mood Elevators)/Thymoleptics
The drugs which improve the moods of depressed individuals are called antidepressants. For example, imipramine, desipramine, amitriptyline, nortriptyline.
Tranquillizers
The drugs which produce calming and quietening effect on the individuals are called tranquillizers. For example, chlorpromazine, haloperidol.
3 Define and classify Antipsychotics/Psychoactive drugs/Psychotropic drugs/Tranquillizers with suitable examples.
☞ Psychotropic/Antipsychotic drugs:
The drugs which are used to treat psychiatric disorders are called psychotropic drugs.
Classification of Psychotropic/Antipsychotic drugs:
Typical antipsychotics: These drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors.
Phenothiazines, e.g. chlorpromazine, trifluoperazine, thioridazine, fluphenazine.
Butyrophenone derivatives, e.g. haloperidol, droperidol, penfluridol.
Thiothixene derivatives, e.g. thiothixene, flupenthixol, chlorprothixene.
Miscellaneous, e.g. reserpine (Rauwolfia alkaloids), loxapine,
molindone.
Atypical Antipsychotics:
For example, olanzapine, clonazepine, quetiapine, lurasidone, risperidone, sertindole, sulpiride.
4 Give the structure, chemical name, properties, stability and storage, uses, formulations and brand names of following Antipsychotics agents. (1) Chlorpromazine,
(2) Haloperidol, (3) Risperidone, (4) Sulpiride, (5)
Olanzapine and (6) Quetiapine.
☞ 1. CHLORPROMAZINE
It is a phenothiazine derivative.
Structure:
Chemical Name:
2-chloro,10(3-dimethyl amino propyl) phenothiazine.
Properties
It is a white or cream-coloured powder with slight odour.
It is very soluble in water and freely soluble in alcohol.
It is decomposed on exposure to light becoming yellow-pink and finally violet.
Stability and Storage
It is discoloured when exposed to light and hence it is stored in a well closed light-resistant container.
Uses
It is an antipsychotic agent and used to treat schizophrenia, mania, etc.
It is used to control nausea and vomiting.
It is used to produce pre- and postoperative sedation.
It is a vasodilator and reduces blood pressure.
It also reduces salivary and gastric secretions.
It has a local anaesthetic property.
It produces hypothermia condition.
It produces tranquillizing effect.
☞ Pharmaceutical Formulations:
Chlorpromazine tablet.
Chlorpromazine injection.
Chlorpromazine elixir.
Chlorpromazine suppositories.
Brand Names
Largactil, Megatil, Sunprazin, Chlorozine, Clozine, Talentil-T, Talentil forte.
HALOPERIDOL
It is a butyrophenone derivative.
Structure:
Chemical Name:
4 [4 (p-chlorophenyl) 4-hydroxy piperidine] 4-fluoro-butyrophenone.
Properties
It is a white to faint yellowish, amorphous powder.
It is odourless and tasteless.
It is practically insoluble in water.
It is sparingly soluble in alcohol.
Storage
It is stored in a well-closed container and protected from light and do not freeze.
Uses
It is a major tranquillizer and is used to treat acute schizophrenia, mania, severe anxiety, etc.
It is used as antiemetic.
It potentiates the actions of CNS depressants like analgesics,
barbiturates.
☞ Pharmaceutical Formulations:
Haloperidol tablet.
Haloperidol injection.
Haloperidol capsule.
Haloperidol elixir.
Haloperidol oral suspension.
Strong haloperidol oral suspension.
Brand Names
Halidol, Trancodol, Peridol, Mindwel, Senorm, Cizoren.
RISPERIDONE (Benzisoxazole derivative)
Risperidone is a member of the class pyridopyrimidine
Structure:
Chemical Name:
3-[2-[4-(6-fluoro-1,2-benzoseazol-3-yl)-1-piperidinyl] ethyl]-2-methyl - 6,7,8,9 tetrahydropyrido [1,-2-a] pyrimidine-4-one
Properties
It is a white slightly beige powder.
It is practically insoluble in water, freely soluble in methylene chloride
It is soluble in methanol and 0.1 NHCl.
Stability and Storage
It should be stored in a well-closed container at temperature not more than 25°C for not more than 7 days.
Uses
It is widely used in the treatment of mania and schizophrenia.
It is used as antipsychotic.
Risperidone is used to treat bipolar disorders or instability associated with acoustic disorder.
It helps to decrease the negative (e.g. withdrawl, apathy) as well as the positive (e.g. delusions, hallucinations) symptoms of schizophrenia.
☞ Pharmaceutical Formulations:
Risperidone tablet
Risperidone oral solution
Risperidone injection
Brand Names
Riperdal, Respolept, Donforte, Risperdal M.
SULPIRIDE
It is a derivative of benzamides.
Structure:
Chemical Name:
RS-5-(Aminosulphonyl), N-[(1-ethyl, 2-pyrrolidinyl) methyl] 2-methoxy benzamide.
Properties
It is a white-yellowish crystalline, solid powder with lemon
odour.
It is sightly soluble in water.
It is soluble in ethanol and 0.1 NHCl.
Stability and Storage
It should be stored in tightly closed container in cool, dry and well ventilated place.
Uses
Used in the management of symptoms of schizophrenia.
As a antipsychotic/psychotropic and antiemetic.
Used in the treatment of dysthymia (depressive disorder).
It accelerate antidepressant response in patients with major depressive disorders.
Used in the treatment of panic disorders.
☞ Pharmaceutical Formulations:
Sulpiride tablets.
Sulpiride oral solutions.
Sulpiride injection.
Brand Names
Sulpiride, Aiglonyl, Dogmatil, Eglonyl, Espiride, Sulpor.
Dose
400 to 800 mg daily.
OLANZAPINE
It is a benzodiazepine derivative.
Structure:
Chemical Name:
2-methyl-4-(4-methyl-1-piperazinyl)-10-H-thieno [2,3-b], [1,5] benzodiazepine.
Properties
It is a yellow crystalline powder.
It is practically insoluble in water.
It is sparingly soluble in acetonitrile, ethyl acetate and
soluble in chloroform
Stability and Storage
It should be stored in well closed container protected from light and moisture at room temperature.
Uses
Used as antipsychotic.
To treat the symptoms of schizophrenia.
Olanzapine rebalances dopamine and serotonin to improve thinking, mood and behaviour.
It is useful for the treatment of anxiety and depression.
It is added to mood stabilizers to enhance their antimanic efficacy.
☞ Pharmaceutical Formulations:
Olanzapine tablets.
Olanzapine injection.
Brand Names
Cinol Plus, Dopin, Cypine, Oleanz, Zyprexa, Dopine-F.
QUETIAPINE FUMARATE
Quetiapine is a second-generation atypical antipsychotic used in schizophrenia, major depression, and bipolar disorder. Quetiapine demonstrates a high level of therapeutic efficacy and low risk of adverse effects during long-term treatment. It is well-tolerated and a suitable option for some patients with high sensitivity to other drug.
Structure:
Chemical Name:
2-[2-(4-dibenzo (b,f) [1,4] thiazepin-11-yl-1-piperazinyl)ethoxy]-
ethanol furmarate.
Properties
It is white to off-white powder.
It is odourless.
It is slightly soluble in ethanol, very slightly soluble in acetone, water and insoluble in acids.
Stability and Storage
It should be kept in well-closed container and well-ventilated placed at room temperature.
Uses
It is used to treat certain mental/mood disorders such as schizophrenia, bipolar disorder, sudden episodes of mania or depression.
To treat depression that can help to prevent suicidal thoughts/ attempts and provide other important benefit.
It is used as psychotropic/antipsychotic agent.
☞ Pharmaceutical Formulations:
Quetiapine tablet.
Quetiapine pills
Brand Names
Seroquel, Q-Pin, Pincalm, Adequet, Placidin, Queviz-100.
LURASIDONE
It is a 1,2- benzisothiazole derivative.
Structure:
Chemical Name:
(3aR, 4S, 7R, 7aS)-2-{(1R,2R)-2-[4-1,2-benzisothiazol-3-yl] pip-erazin-1-y1-methyl cyclohexy methyl} hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride.
Properties
It is a white to off-white powder.
It is odourless.
It is sparingly soluble in methanol, slightly soluble in
ethanol.
It is very slightly soluble in acetone, water and practically insoluble in 0.1NHCl and toluene.
Stability and Storage
It should stored in a tightly closed container in a dry and well ventilated place at a temperature 25°C.
Uses
Lurasidone is used to treat psychic disorders (as antipsychotic)
It is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking loss of interest in life) in adults and children 13 years of age and older.
It may also help to decrease hallucinations.
Lurasidone rebalances, dopamine and serotonin to improve thinking mood and behaviour.
It is also used to treat bipolar disorders.
☞ Pharmaceutical Formulations:
Lurasidone tablet.
Lurasidone injection
Brand Names
Latuda, Luratrend, Atlura, Tablura.
Dose
40 mg once daily.
Anticonvulsants/
Antiepileptics
1 What is epilepsy? Explain various types of epilepsy.
☞ Epilepsy/Seizures:
It is a chronic convulsive disorder characterised by sudden disturbance of consciousness usually but not always with characteristic body movements and sometimes with autonomic hyperactivity.
The term epilepsy is derived from the Greek word “Epilabanein” which means to seize (i.e. to take sudden possession).
Epilepsy is the most common neurological disorders characterized by paroxysmal cerebral dysrhythmia.
Seizures are symptoms of disturbed electrical activity in the brain characterized by episodes of abnormal, excessive and synchronus discharge of a group of neurons within the brain that causes involuntary movement, sensation or thought.
☞ Types of Epilepsy
Grand mal epilepsy: It involves a sudden loss of consciousness and major convulsions consisting of spasms of the whole body followed by jerky movements. Convulsions are followed by generalised CNS depression.
Temporal lobe epilepsy: It consists of sudden attacks of altered behaviour and emotions. Convulsions are absent
The entire attack consists of abnormalities of behaviour.
Focal cortical epilepsy: It consists of convulsions of single limb or a group of muscles.
Minor epilepsy: It consists of loss of consciousness without convulsions.
Petit mal epilepsy: It consists of impairment of consciousness
associated with eyelid blinking (insensitivity of light).
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Myoclonic epilepsy: It consists of isolated clonic jerks.
Infantile epilepsy: It occurs in infants and consists of mental deterioration.
Motor epilepsy: It involves involuntary movements of thumb, angles of mouth, movements of half side of the body may be affected like paralysis.
2 Define and classify antiepileptics/anticonvulsants with
suitable examples.
The drugs which are used in the treatment of various types of epilepsy
are called antiepileptics/anticonvulsants.
☞ Classification
Hydantoin derivative, e.g. phenytoin, ethoin, methoin.
Barbiturates, e.g. phenobarbitone, mephobarbitone.
Benzodiazepine, e.g. diazepam, nitrazepam.
Iminostilbene/Dibenzazepine derivative, e.g. carbamazepine.
Carboxylic acid derivative, e.g. sodium valproate (valproic acid).
Succinimides, e.g. ethosuximide, phensuximide.
Oxazolidine dione derivative, e.g. paramethadione.
Deoxy barbiturates, e.g. primidone
Phenyltriazine, e.g. lamotrigine
Cyclic GABA analogue, e.g. gabapentin.
Newer drugs: Vigabatrin, topiramate, zonisamide, tiagabine.
3 What is hydantoin? Name any three drugs which belong to hydantoin. Explain any one.
Hydantoin is imidazolidine 2,4-dione. For example, phenytoin,
ethoin, methoin.
☞ PHENYTOIN
It is a hydantoin (i.e. imidazolidine 2,4-dione) derivative.
Structure:
Chemical Name:
5,5-diphenyl imidazolidine 2,4-dione or 5,5-diphenyl hydantoin
Properties
It is a white crystalline powder and is odourless.
It is very slightly soluble in water.
It is slightly hygroscopic.
Stability and Storage
It should be stored in a tightly closed container.
Uses
It is used as an antiepileptic.
It is used to control status epilepticus.
It is used as an antiarrhythmic agent.
It is used in the treatment of migraine.
It is used in the treatment of myotonia.
It is used to treat trigeminal neuralgia.
☞ Pharmaceutical Formulations:
Phenytoin tablet.
Phenytoin capsules.
Phenytoin injections.
Phenytoin oral suspension.
Phenytoin and phenobarbitone tablets.
Brand Names
Eptoin, Epileptin, Garoin, Epanutin, Phenytek.
Dose
0–15 mg/kg or 15–20 mg/kg at 25–50 mg/min.
4 Give the structure, chemical name, properties, stability and storage, uses, formulation, brand names of following anticonvulsant drugs. (a) Carbamazepine,
(b) Clonazepine, (c) valproic acid (d) Gabapentin, (e) Topiramate, (f) Vigabatrin, (g) Lamotrigine.
☞ (a) Carbamazepine
It is a dibenzazepine derivative.
Structure:
Chemical Name:
5H-dibenz [b,f] azepine-5-Carboxamide.
Properties
It occurs as a white or yellowish white crystalline powder.
It is odourless with slightly bitter taste.
It is practically insoluble in water and soluble in alcohol, chloroform and acetone.
Storage
It should be stored in a well tightly closed container and protected from light.
☞ Pharmaceutical Formulations:
Carbamazepine tablet IP, BP.
Carbamazepine injection
Carbamazepine suppositories
Brand Names
Tegretol, Epitol, Tegretol XR.
Clonazepam
It is a dibenzazepine derivative.
Properties
It is off-white to light yellow crystalline powder.
It has faint odour.
It is insoluble in benzene.
It is slightly soluble in acetone, methanol, and chloroform.
Stability and Storage
It is kept in tightly closed container in a dry and well-ventilated place, in light-resistant containers at 25°.
Uses
It is used as an anticonvulsant/antiepileptic.
It is used to control seizures or fits due to epilepsy, involuntary muscle spasms, panic disorders and sometimes restless legs syndrome.
Valproic Acid
Structure:
Chemical Name:
2-propyl pentanoic acid
Properties
It is hygroscopic in nature.
It is clear colourless liquid with characteristic odour.
It is freely soluble in 1N sodium hydroxide, methanol, alcohol, acetone, chloroform, benzene, ether and slight soluble in 0.1N hydrochloric acid.
Stability and Storage
It should be stored in tightly closed container and stored between the temperature range of 15°C and 30°C.
Uses
It is used as an anticonvulsant.
It is used to treat bipolor disorder.
It is used to prevent migraine headache and to treat epilepsy.
It works by restoring the balances of neurotransmitters in the
brain.
☞ Pharmaceutical Formulations:
Valproic acid tablet
Valproic acid injection
Valproic acid syrup
Brand Names
Depacan, Epilim, Stavzor, Depakene.
Gabapentin
Structure:
Chemical Name: 2-(1-(aminomethyl) cyclohexyl) acetic acid
Properties
It is a white to off-white crystalline solid crystals.
It has bitter taste.
It is freely soluble in water, alkaline and acidic solutions.
Stability and Storage
It should be kept in tightly closed container in dry and well-venti-lated place in two temperature ranges between 15°C and 30°C. Oral solution must be refrigerated at 2° to 8°C.
☞ Pharmaceutical Formulations:
Gabapentin tablet.
Gabapentin oral solution.
Gabapentin capsule
Gabapentin injection
Brand Names
Gabarone, Neurontin, Fanatrex, FusePaq, Gralise.
Dose
Maximum dose is 2400 to 3600 mg/day, in divided doses.
Topiramate
It is a carbonic anhydrase inhibitor.
Properties
It is a white crystalline powder.
It has a bitter taste.
It is soluble in most alkaline solutions containing sodium hydroxide and having pH 9 to 10.
It is freely soluble in acetone, chloroform, ethanol.
Stability and Storage
It should be stored in tight, light-resistant container. It should be stored at controlled room temperature or in a refrigerator.
Uses
It is used to treat epilepsy.
It is used to treat migraine headache.
It is used to treat generalized or focal seizures.
☞ Pharmaceutical Formulations:
Topiramate tablet
Topiramate injection
Topiramate oral suspension
Brand Names
Topamax, Trokendi XR, Qudexy XR.
Vigabatrin
It is a structural anologue of GABA.
It works by inhibiting the breakdown of g-aminobutyric acid.
It is also known as g-vinyl-GABA.
Properties
It is a white to off-white powder.
It is freely soluble in water.
It is slightly soluble in methanol, alcohol.
It is very slightly soluble in ethyl alcohol and chloroform.
It is insoluble in toluene and hexane.
Stability and Storage
It should be stored in amber coloured glass and PET bottles which are stored under three different conditions is at room temperature (15 to 30°C), under refrigeration (2 to 8°C) and oven (40°C).
Uses
It is used to treat epilepsy.
It controls infantile spasms.
As anticonvulsant.
In combination with other medications it is used to treat complex partial seizures in adults.
☞ Pharmaceutical Formulations:
Vigabatrin tablet.
Vigabatrin syrup
Brand Names
Sabril, Vigadrone.
Lamotrigine
It is a synthetic phenyltriazine.
Properties
It is a white to pale cream coloured powder.
It is very slightly soluble in water
It is slightly soluble in 0.1 M HCl.
Stability and Storage
It should be kept in tightly closed container in dry and well-ventilated
place.
Uses
It is used to treat epilepsy.
It is used to prevent recurrence of depressive episodes in
bipolar disorders.
It is used to treat anxiety depression, migraine.
☞ Pharmaceutical Formulations:
Lamotrigine tablet.
Lamotrigine oral suspension.
Brand Names
Lamictal, Lamictal XR, Subvenite, Lamictal CD.
Antidepressants
1 What is depression? Name the drugs used in the treatment of depression?
☞ Depression:
Depression is a mental illness characterized by pathological changes in mood.
Depression is a sadness, though possibly intense, it is usually of short duration.
Symptoms of Depression:
Fatigue.
Headache
Insomnia
GIT disturbances
Anorexia
Skeletomuscular complaints
Loss of sexual desire.
Drugs used in treatment of depression are:
Antidepressants/mood elevators/Thymoleptics
For example: Imipramine, amitriptyline, doxepin fluoxetine, duloxetine, sertraline, citalopram, fluvoxamine, paroxetine, phenelzine, tranylcypromine, dibenzepin.
2 Define and classify antidepressants (mood elevators/ thymoleptics) with examples.
☞ Antidepressants:
The drugs which counteract or overcome the mental depression are
called antidepressants.
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The drugs which elevate/improve the mood of depressed individuals are called antidepressants.
The drugs which are used in the treatment of depression are
called antidepressants.
☞ Classification of Antidepressants:
Tricyclic Antidepressants:
For example: Imipramine, desipramine, doxepin, anitriptyline,
nontriptyline.
Mono-Amino-Oxidase Inhibitors (MAOIs):
For example: Phenelzine, tranylcypromine, isocarboxazid,
moclobemide.
Selective Serotonin Reuptake Inhibitors (SSRIs):
For example: Fluoxetine, sertraline, citalopram, escitalopram.
Dopamine and Norepinephrine Reuptake Inhibitors (DNRIs):
For example: Bupropion.
Mood Stabilizers:
For example: Lithium Carbonate.
Miscellaneous:
(a) b-adrenorecepter agonist, e.g. salbutamol.
(b) Thyrotropin releasing hormone (TRH)
3 Give the structure, chemical names, properties, stability and storage, uses, pharmaceutical formulations, brand names of following antidepressants. (a) Anitriyptyline
(b) Imipramine (c) Fluoxetine.
☞ (a) Anitriptyline
It is a tricyclic antidepressant.
Structure:
Chemical Name:
N, N-dimethyl-3-(2-tricyclo [9.4.0.03.8] pentadeca-1 (15), 3, 5, 7, 11, 13-hexaenylidene) propan-1-amine; hydrochloride.
Properties
It is a white or off-white solid, brownish crystal.
It is slightly basic in nature.
It is freely soluble in water and alcohol.
It is insoluble in other organic solvents.
Stability and Storage
It should be kept in a tightly closed container in a dry and well-ven-tilated place temperature 2°–8°C and keep in a dry place.
Uses
It is used as antidepressant.
It is used to treat nerve pain, backpain.
It has sedative property.
It is also used as anticholinergic.
It is used to treat:
Endogenous depression.
Anxiety.
Nocturnal enuresis (bed wetting in children)
In migraine pain
Pharmaceutical Formulations:
Amitriptyline tablet.
Amitriptyline injection.
Amitriptyline and perphenazine capsules.
Amitriptyline oral suspension.
Brand Names
Tryptanol, Amiline, Quietal, Amitone, Amitor, Eliwel.
Imipramine
It is a tricyclic antidepressant and is a dibenzazepine derivative.
Structure:
Chemical Name:
10,11 dihydro, 5 (3-dimethyl amino propyl) 5[H] dibenz (b,f) azepine
Properties
It is a white or slightly yellow crystalline powder.
It is odourless and has bitter taste.
It is freely soluble in water.
It is less soluble in alcohol, sparingly soluble in a acetone.
Stability and Storage
It is affected by moist, air and light. Hence it is stored in tightly
closed light-resistant containers.
Uses
It is used to treat chronic depression.
It is used to treat anxiety disorders.
It is used to treat pains due to its analgesic property.
It is used to treat hyperactivity and disturbed attention.
It is used to treat allergic conjunctivitis.
To treat enuresis (bed wetting in children)
Preparations
Imipramine tablet.
Imipramine injection.
Imipramine mixture.
Imipramine capsule.
Brand Names
Antidep, Depranil, Depsonil, Impratab.
Fluoxetine
Structure:
Chemical Name:
N-methyl-3-phenyl-3-[4-(trifluoromethyl) phenoxy] propan-1-amine
Properties
It is a white to off-white crystalline solid powder.
It is soluble in methanol, ethanol.
It is partially soluble in acetone, chloroform, sparingly soluble
in dichloromethane.
It is insoluble in ethyl acetate, toluene, cyclohexane and
hexane.
Stability and Storage
It should be stored in tight, light-resistant container at 15°–30°C.
Uses
It is used as antidepressant.
It is used to treat obsessive compulsive disorder and bulimia
nervosa (eating disorder).
Fluoxetine helps many people recover from depression and it has fewer unwanted effects than older anti-depressants.
Pharmaceutical Formulations:
Fluoxetine tablet.
Fluoxetine capsule.
Fluoxetine oral solution.
Brand Names
Flunil, Dawnex, F-Tin, Prodep, Prozac.
4 Write a note on following antidepressant drugs.
☞ (a) Venlafaxine:
Physical Properties:
It is a white or off-white crystalline solid.
It is soluble in water and methanol.
Stability and Storage
It should be stored at controlled room temperature of 20° to 50°C.
Uses
Venlafaxine is used to treat depression.
It may improve the mood and energy level and may help to
restore the interest of the individual in daily living.
Venlafaxine is known as a serotonin-norepinephrine reuptake
inhibitor.
It is also used to treat anxiety and panic attacks.
Pharmaceutical Formulations:
Venlafaxine tablet.
Venlafaxine capsule.
Venlafaxine injection
Brand Names
Envelaf-XR, Venlor, Ventab, Sentosa, Flavix, Effexar, Venlift.
Duloxetine:
Properties:
It is a white to slightly brown colour solid crystals.
It is acid labile, soluble in water, and methanol.
It is insoluble in other neutral organic solvents.
Stability and Storage
It should be stored in a tightly closed container in a dry and well
ventilated place.
Pharmaceutical Formulations:
Duloxetine tablet.
Duloxetine capsule.
Duloxetine injection.
Brand Names
Cymbalta, Cambac, Dulane, Irenka, Delok, Ambidext.
Sertraline:
Properties:
It is a white solid crystal or powder.
It is soluble in water and slightly soluble in isopropyl alcohol.
Stability and Storage
It should be stored in a tightly closed container at room temperature.
Uses
It is used as antidepressant.
It is used to control panic attacks.
It is used to treat obsessive compulsive disorder (OCD).
Is is used to treat post-traumatic stress disorder (PTSD).
Pharmaceutical Formulations:
Sertraline Tablet.
Sertraline oral concentrate.
Brand Names
Serdep, Inosert, Serlift, Sertima, Asert, B-Sert, Censir, Atline, Aderta.
Citalopram:
Properties:
It is a solid, fine white to off-white crystals with fart odour.
It is freely soluble in water, ethanol, chloroform.
Citalopram, when heated to decomposition, it emits very toxic fumes of nitrogen oxides, hydrogen fluoride and hydrogen bromides.
Stability and Storage
It should be stored in a well-closed container in a dry and well-
ventilated place.
Uses
Citalopram is used as antidepressant drug.
It is also used to control panic attacks.
It is a selective serotonin reuptake inhibitor.
Pharmaceutical Formulations:
Citalopram tablet.
Citalopram capsule.
Citalopram injection
Brand Names
C-Talo, Celica, Citadep, Akarin, Celepra, Celexa, C-Pram.
Escitalopram:
Properties:
It is a fine white to slightly yellow powder.
It is freely soluble in methanol and dimethylsulfoxide (DMSO).
It is soluble in isotonic saline solution.
It is sparingly soluble in water and ethanol.
It is slightly soluble in ethylacetate and insoluble in heptane.
Stability and Storage
It should be stored in a well closed container at room temperature, and kept away from heat, moisture and direct light.
Uses
It is used as antidepressant.
It is used for treatment of anxiety.
It is used to treat obsessive compulsive disorder or panic
attacks.
Pharmaceutical Formulations:
Escitalopram tablet.
Brand Names
Stalopam, S-Citadep, Szetalo, Nexito.
Fluvoxamine:
Properties:
It is a solid, fine white-yellowish, odourless crystals.
It is sparingly soluble in water.
It is freely soluble in ethanol and chloroform.
It is practically insoluble in diethyl ether.
Stability and Storage
It should be stored in a tightly closed container protected from high humidity and stored at 20° to 25°C.
Pharmaceutical Formulations:
Fluvoxamine tablet.
Fluvoxamine capsule.
Brand Names
Fluvoxin-CR, Fluvator, Uvox, Voxamin, Frext.
Paroxetine:
Properties:
It is a off-white powder.
It is a odourless.
It has an inherently bitter taste.
It is having a melting point range of 120° to 138°C.
Stability and Storage
It should be stored in a well-closed container at room temperature from 15° to 30°C.
Pharmaceutical Formulations:
Paroxetine tablet.
Paroxetine capsule.
Brand Names
Paxil-CR, Pexeva, Brisdelle.
Uses
Antidepressant
Nervous System
A Sympathomimetics/Adrenergic Agents.
B Anti-adrenergics/Sympatholytics/ Adrenergic Antagonists.
C Parasympathomimetics/ Cholinergics Drugs.
D Cholinergic Blocking Agents/ Anticholinergics/Parasympatholytic.
Introduction To ANS:
ANS means autonomic nervous system.
ANS controls the activities of involuntary/internal organs of the body like heart, blood bessels, bronchioles, smooth muscles etc.
ANS consists of two divisions: (a) Sympathetic nervous system (SNS) and (b) parasympathetic nervous system (PSNS).
Sympathetic Nervous System (SNS):
It enhances heart rate and force of contraction and dilates the bronchi.
It helps to release the stored energy.
It shows down the digestion and urination activities
Parasympathetic Nervous System (PSNS):
It conserves and restores the energy from the processed food which is used to build tissues.
It slows the heart rate and decreases blood pressure.
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Neurotransmitters/chemical transmitters:
Acetylcholine is a chemical transmitter of PSNS.
Adrenaline is a chemical transmitter of SNS.
Classification of the drugs acting on ANS:
Sympathomimetics/ Adrenergic Agents
A
1 Define and classify sympathomimetics with examples.
☞ Sympathomimetics
“The drugs which produce actions similar to stimulation of sympathetic nerve stimulation are called sympathomimetics or adrener-gics.”
Classification of Adrenergics:
Classification on chemical basis
Catecholamines, e.g. adrenaline, nor-adrenaline, isoprenaline.
Noncatecholamine, e.g. amphetamine, ephedrine, phenylephrine pseudoephedrine, terbutaline.
Imidazolidine derivative, e.g. naphazoline.
Classification on the Basis of Mechanism of Action:
Direct Acting Drugs:
For example: Norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine, methyldopa, clonidine, dobutamine, isoproterenol, terbutaline, salbutamol, bitolterol, naphazoline, oxymetazoline, xylometazoline.
Indirect Acting Drugs:
For example: Hydroxyamphetamine, pseudoephedrine, pro-pylhexedrine,
Agents with mixed mechanism:
For example: Ephedrine, metaraminol.
2 What are catecholamines? Name any two catecholamines and describe them along with structures.
Catecholamines: The drugs which contain catechol nucleus with
alkylamine are called catecholamines, e.g. adrenaline, nor-adrenaline, isoprenaline.
5 6
4
1
3 2
HO Catechol (3,4-dihydroxy phenyl)
HO
(1) Adrenaline/Epinephrine
Structure
4
1
5 6
3 2
1 2
HO CH
OH
HO
CH2 NH CH3
Chemical Name
1(3,4-dihydroxyphenyl) 2methyl amino ethanol
Properties
It is white or creamy white microcrystalline powder.
It is odourless and bitter in taste.
It is very slightly soluble in water but practically insoluble in alcohol.
It is levorotatory.
Stability and Storage
It darkens on exposure to light and air. Hence, it is stored in tightly closed light-resistant container.
Uses
It is used:
In the treatment of bronchial asthma.
To treat heart block.
To treat acute allergic conditions.
To control superficial haemorrhage of nose and throat.
With local anaesthetic to prolong local anaesthetic effect.
Used to treat open angle glaucoma.
Pharmaceutical formulations
Adrenaline tartrate injection.
Adrenaline eyedrops/solutions.
Adrenaline and atropine spray.
Zinc sulphate and adrenaline eye drops BP.
Adrenaline bitartrate IP.
Brand Names
Adrenar, Nordrin, Medicreme, Epipen, Epinal, Epifrin, Rephon.
(2) Nor-epinephrine (Nonadrenaline):
It is a naturally accuring catecholamine
Structure:
Chemical Name:
L-1(3,4 dihydroxy pheny) 2amino ethanol. OR
4-(2 amino1hydroxy methyl) benzene1, 2diol.
Properties:
It is a white or creamy white microcrystalline powder.
It is odourless and bitter in taste.
It is very slightly soluble in water but practically insoluble in alcohol.
It is levorotatory.
Stability and storage:
It darknes an exposure to light air. Hence, it should be stored in tightly closed light-resistant containers.
Uses:
It is used.
To treat heart block (cardiac arrest).
To control superficial haemorrhage of nose and throat.
With local anaesthetics, to prolong local anaesthetic effect.
Used in peripheral vascular collapse.
To maintain blood pressure in acute hypotensive states.
Used during CPR.
Pharmaceutical formulations:
Norepinephrine injection.
Sterile strong norepinephrine solution.
Brand Names:
Levophed, Levarterenol.
3 Draw the structure and give chemical name, properties, stability, storage, uses, pharmaceutical formulations, brand names of following adrenergic drugs: (a) Dopamine, (b) Naphazoline.
☞ (a) Dopamine:
Dopamine is a naturally occuring catecholamine formed by de-carboxylation of dihydroxy phenylalanine and a precursor of norephinephrine and epinephrine.
Dopamine is a monoamine compound with positive ionotropic activity.
Structure:
Chemical Name: 4-(2aminoethyl) benzene1, 2, diol.
Properties:
It is a white crystalline solid particles.
It is freely soluble in water, methanol and hot 95% ethanol.
It is practically insoluble in ether, petroleum ether, chloroform, benzene and toluene.
Stability and storage:
Dopamine hydrochloride 0.5 mg/ml in isotonic glucose solution is stable when protected from light for 1 week at 25°C/60% relative humidity and for 3 months at 4°C/ambient humidity in Codan and Braun syringes.
Uses:
Dopamine is used to treat low blood pressure (hypotension)
It is used to treat low cardiac ouptut and improves blood flow to the kidneys.
Dopamine is frequently administered in the ICU to critically ill patients.
Dopamine is used to treat reduced perfusion of body organs due to shock, trauma and sepsis.
Dopamine is used as prophylaxis for the improvement of kidney and bowel perfusion.
Dopamine is a neurotransmitter that plays several important roles in the brain and body.
Pharmaceutical formulations:
Dopamine hydrochloride injection USP.
Brand Names:
Komidop, Dopastat, Intropin, Revimine Dopacard, Dopinga.
(b) Naphazoline:
Structure:
Chemical Name: 2-(naphthalene1yl) 4, 5dihydro1 Himidazole.
Properties:
It is a white crystalline powder.
It is odourless with bitter in taste.
It is hygroscopic in nature.
It is freely soluble in water, soluble in ethanol.
Stability and storage:
It should be stored in dropper bottle upright at room temperature between 20°C and 25°C away from moisture and sunlight and do not store in moist place. Discard if drops become discoloured or cloudy and keep all medicines away form children.
Uses:
Naphazoline is used as ophthalmic. decongestant.
It is used for temporary relief of eye redness, puffiness, itching and watering that commonly occurs with allergies.
It has a vasoconstrictor action.
It works by narrowing of swollen blood vessels in the eyes to reduce eye redness.
Pharmaceutical formulations:
Naphazoline ointment.
Naphazoline eye drops.
Naphazoline nasal drops.
Brand Names:
Napzol, N-zolin, Ncool, Naphcon, Privine, Ocucel. Mezol, ENorm, Clearine.
4 Write a note on the following adrenergic drugs.
(a) Phenylephrine, (b) Terbutaline, (c) Salbutamol (albuterol), (d) Tetrahydrozoline, (e) Hydroxy amphetamine, (f) Ephedrine, (g) Pseudoephedrine and (h) Metaraminol.
☞ (a) Phenylephrine:
Properties
It is a white crystalline powder.
It is odourless and has bitter taste.
It is freely soluble in water.
Stability and Storage
It is stored in tightly closed light-resistant containers.
Uses
It is used:
In bronchial asthma.
In heart block, mydriatic.
Locally in nasal congestion.
To relieve nasal discomfort caused by colds, allergies and hay fever.
To relieve sinus congestion and pressure.
Topically to prevent symptoms of haemorrhoids.
As a eye drop to dialate the pupil.
Preparations
Phenylephrine injection.
Phenylephrine eye drops.
Brand Name
Biomydrin, Deconasal CT, Histinextic, Neo-synephrine, Vicoryl, Codylex.
Terbutaline:
Properties:
It is a white to gray-white crystalline powder.
It has slightly bitter taste.
It is soluble in water, slightly soluble in alcohol, methanol.
It is practically insoluble in chloroform and ether.
Stability and storage:
It should be kept in a tightly closed container at room temperature and away from excess heat and moisture.
Uses:
It is used to treat bronchospasm in bronchial asthma and chronic bronchitis.
In emergency, it is used to treat cardiotoxic shock states, heart block or severe bradycardia.
Terbutaline is used to prevent and treat wheezing shortness of breath and chest tightness caused by asthma, chronic bronchitis and emphysema.
It works by relaxing and opening the airways, making it easier to breathe.
Pharmaceutical formulations:
Terbutaline tablet.
Terbutaline syrup.
Terbutaline injection.
Terbutaline inhaler.
Salbutamol (Albuterol)
Properties
It is a white crystalline powder.
It is odourless and tasteless.
It is sparingly soluble in water.
It gives reddish orange colour with FeCl3 solution.
It is insoluble in chloroform and ether.
Stability and Storage
It is light sensitive and hence it is stored in a well-closed lightresis-tant container.
Uses
It is used:
In bronchial asthma.
In heart block.
In locally nasal congestion.
In prevention of premature labour.
In chronic bronchitis.
In chronic bronchopulmonary disorders.
To prevent coughing, wheezing and feeling breathless.
Preparations
Salbutamol tablet.
Salbutamol injection.
Salbutamol aerosol.
Salbutamol inhalation.
Salbutamol syrup.
Salbutamol inhaler.
Salbutamol rotacap.
Brand Names
Asthalin, Ventolin, Salbetol, Asmanil, Aerotaz Disk, Bronkotab.
Tetrahydrozoline:
Properties:
It is colourless, odourless and tastless crystalline powder.
It is very soluble in water and ethanol slightly soluble in chloroform and insoluble in diethyl ether.
Stability and storage:
The drops should generally be stored in a cool dry place.
Uses:
It is used to prevent redness in the eyes caused by minor eye irritations.
It works by temporarily narrowing the blood vessels in the eye.
Pharmaceutical formulations:
Tetrahydrozoline eye drops.
Tetrahydrozoline ear drops.
Brand Names:
Eyesine, Murine Tears Plus, Tyzine, Geneye.
Hydroxyamphetamine:
Properties:
It is a white to yellowish crystalline solid and strongly basic compound.
It is more soluble in water.
It is slightly soluble in methanol.
Stability and storage:
It should be stored in well-closed container at room temperature and protected from light.
Uses:
In ophthalmics used for relaxation of eye muscles.
It dilates the pupils in an inflammatory condition or in postsur-gery situations.
Pharmaceutical formulations:
Hydroxyamphetamine eye drops.
Hydroxyamphetamine ointment.
Brand Names:
Paremyd, paredrine.
Ephedrine
Ephedrine is an alkaloid obtained from the species of Ephedra.
Properties
It is a white crystalline powder.
It is odourless and has bitter taste.
It is sparingly soluble in water.
It is levorotatory.
Stability and Storage
It gradually decomposes on exposure to light. Hence it should be stored in tightly closed light-resistant container.
Uses
It is used:
In bronchial asthma.
In nocturnal enuresis.
As a nasal decongestant.
In treatment of narcolepsy.
In the treatment of narcolepsy.
As a bronchodialator.
For temporary relief of shortness of breath, chest tightness and wheezing due to bronchial asthma.
Pharmaceutical formulations
Ephedrine tablet.
Ephedrine elixir.
Ephedrine nasal drops.
Ephedrine sulphate syrup.
Ephedrine hydrochloride tablet BP.
Ephedrine capsule.
Brand Name
Ephedrex, Akovaz, Corphedra.
Pseudoephedrine:
Properties:
It is white, odourless crystals or powder with bitter in taste.
It has a slight aromatic odour.
It is acidic in nature.
It is completely soluble in water, methanol and partially soluble in chloroform.
Stability and Storage
It should be stored at room temperature and kept away from moisture and heat. It should be kept in tightly closed container away from the reach of the children.
Uses:
It is used in the treatment of common cold, flu, etc.
It is used in breathing illnesses such as hay fever, allergies, bronchitis.
It is used to prevent ear pain and blockage caused by pressure changes during air travel or underwater diving.
It works by narrowing the blood vessels to decrease swelling and congestion.
Pharmaceutical formulations:
Pseudoephedrine tablet.
Pseudoephedrine capsule.
Pseudoephedrine syrup.
Pseudoephedrine cream.
Pseudoephedrine gel.
Pseudoephedrine ointment.
Pseudoephedrine injection.
Brand Names:
Sudafed, Tylenol, Advil, Aleve, Claritin, Mucinex, Alavert, Triaminic.
Metaraminol:
Properties:
It is hygroscopic compound.
It is a white crystalline powder.
It is freely soluble in water.
It is slightly soluble in alcohol.
It is practically insoluble in chloroform and ether.
Stability and Storage
It should be stored in a container in carton until contents have been used and should be protected from light and freezing.
Uses:
It is used to prevent and treat acute hypotensive state occuring with spinal anaesthesia.
In treatment of hypotension caused due to haemorrhage, surgical complications and shock associated with brain damage due to trauma.
Metaraminol is the vasoconstrictor of choice for the short-term management of acute hypotension.
Pharmaceutical formulations:
Metaraminol injection.
Brand Names:
Aramine, Metaramin, Pressonex.
Anti-adrenergics/Sympatholytics/ Adrenergic Antagonists
B
1 Define and classify antiadrenergics with suitable examples.
The drugs which block the action produced by stimulation of sympathetic nervous system are called sympatholytics or anti-adrenergics.
Classification
α-adrenergic blockers (α-blockers), e.g. tolazoline, phentolamine, prazosin, phenoxybenzamine, ergotamine, ergotoxin.
β-adrenergic blockers (β-blockers), e.g. propranolol, atenolol, labetalol, practolol, pindolol, metoprolol, carvedilol.
Adrenergic neuron blockers, e.g. guanethidine.
2 Write a note on propranolol.
☞ Propranolol (β-blocker)
Structre
CH3
3 2 1
8
1
CH2 CH CH2 NH
OH
CH
CH3
7 2
6 3
5 4
Chemical Name
1-isopropyl amino, 3 (1naphthyloxy) propan2ol
Properties
It is a white powder.
It is odourless and has bitter taste.
It is soluble in water.
Stability and Storage
It is affected by light and hence it is stored in a well-closed lightre-sistant container.
Uses
It is used to treat:
Cardiac arrhythmia.
Angina pectoris.
Arterial hypertension.
Hyperthyroidism in children.
Symptoms of anxiety.
Preparations
Propranolol tablet.
Propranolol injection.
Brand Names
Inderal, Ciplar, Innopran XL, Hemangeol.
3 Write a note on Atenolol.
☞ Atenolol:
Structure:
Chemical Name:
2-(4[2 hydroxy3(isopropylamino) porpoxy) phenyl] acetamide.
Properties:
It is a white crystalline powder.
It is odourless and has slightly bitter taste.
It is freely soluble in HCl and less soluble in chloroform.
Stability and Storage:
It is should be stored in a cool and dry place, keep away from light.
Uses:
It is used to treat hypertension and arrhythmia.
It is used in the treatment of angina pectoris.
It helps to prevent future heart disease, heat attacks and strokes.
It is used in the treatment of essential hypertension.
Pharmaceutical formulations:
Atenolol tablet.
Atenolol suspension.
Atenolol injection.
Brand Names:
Aten, Betacard, Tenormin, Tenolol, Hipres.
4 Give the properties, stability, storage, uses, pharmaceutical formulations, Brand names of the following adrenergic antagonists. (a) Tolazoline, (b) Phentolamine, (c) Prazosin, (d) Carvedilol, (e) Phenoxy benzamine.
☞ (a) Tolazoline
Properties
It is a white or creamy-white crystalline powder.
It is odourless and has bitter taste.
It is very slightly soluble in water.
It is freely soluble in alcohol.
Stability
It is affected by light and hence it is stored in tightly closed light-resistant containers.
Uses
It is used to treat peripheral vascular disorder.
In Raynaud’s disease.
Used in persistent pulmonary hypertension of the newborn.
It also stimulates gastric secretion.
In treatment of iritis (eye drops).
Pharmaceutical formulations
Tolazoline tablet BP.
Tolazoline eye drops IP.
Brand Names:
Priscol, Tolazolin, Benzazoline, Vasimid, Vasodil, Priscoline.
Phentolamine:
Properties:
It is a white crystalline powder with bitter taste.
It is soluble in water and alcohol.
It is sparingly soluble in chloroform.
It is practically insoluble in acetone and ethyl acetate
Stability and storage:
It should be stored under controlled room temperature of about 15° to 30°C, in the refrigerator at 4°C and in the freezer at 20°C for 6 months.
Uses:
It is used in treatment of hypertension.
It is used in pheochromocytoma.
It is used to treat vasospasm of Raynaud’s disease.
It is used to prevent hypertensive episodes that occur in patients with pheochromocytoma.
Used in combination with papaverine to treat impotence.
Pharmaceutical formulations:
Phentolamine injection.
Phentolamine tablet.
Phentolamine capsule.
Phantolamine syrup.
Phentolamine cream.
Phentolamine ointment.
Brand Names:
Rogitine, Fentanor, Fentosol.
Prazosin
Properties:
It is a solid white or yellow crystalline powder.
It has bitter taste.
It is a derivative of piperazine.
Stability and storage:
It should be stored at room temperature, i.e. 15°–30°C and kept away from direct sunlight.
Uses:
Used in the treatment of hypertension.
It produce peripheral vasodialation.
It helps to prevent strokes, heart attack, and kidney problems.
Pharmaceutical formulations:
Prazosin capsules.
Brand Names:
Prazocip, Minipress, Minizide, Cyber CR, Czopress XL.
Carvedilol
Properties:
It occurs as a colourless solid crystals.
It has unpleasant taste and odour.
It is a hydrophobic compound.
It is freely soluble in dimethyl sulfoxide.
It is soluble in methylene chloride and methanol.
It is sparingly soluble 95% ethanol and isopropanol.
It is slightly soluble in ethyl ether, and practically insoluble in water.
Stability and storage:
It should be stored in well-closed container at 20°–25°C and kept in dry place.
Pharmaceutical formulations:
Carvedilol tablet
Brand Names:
Caditone, Cadomos, Carloc, Cardivas, Carca, Cardinom.
Phenoxybenzamine
Properties:
It is white crystalline compound.
It has bitter taste and slightly aromatic odour.
It is soluble in methanol, chloroform and insoluble in diethyl ether.
Stability and storage:
It should be stored in a room temperature of 20°–25°C.
Uses:
It is used to treat high blood pressure and heavy sweating due to certain tumour of adrenal glands (pheochromocytoma).
Phenoxybenzamine belongs to a class of drugs known as alpha blockers.
It works by relaxing and widening blood vessels so that blood can flow more easily.
Pharmaceutical formulations:
Phenoxybenzamine tablet.
Phenoxybenzamine capsule.
Phenoxybenzamine injection.
Brand Names:
Fenoxene, Dibenzylene, Fenoben.
Parasympathomimetics/ Cholinergic Drugs
C
1 Define and classify parasympathomimetics/
chollinergics?
☞ Cholinergics
The drugs which produce pharmacological actions similar to actions produced by stimulations of parasympathetic nervous system are called cholinergics/cholinomimetics.
The drugs which exert pharmacological actions like acetylcholine or drugs which brings about stimulation of cholinergic nerves are known as cholinergic drugs.
Classification of cholinergic drugs
Direct acting agents/cholinergic agonists:
Ester of choline, e.g. acetylcholine, carbachol, bethae-chol muscarine, pilocarpine.
Indirect acting agents/cholinesterase inhibitors:
Reversible, e.g. physostigmine, neostigmine, pyridostig-mine, edrophonium, tacrine hydrochloride.
Irreversible e.g. echothiophate iodide, parathion, mala-thion.
Cholinesterase reactivators
Pralidoxime chloride.
2 Give the structure, chemical name, properties and uses of neostigmine.
☞ Neostigmine
Properties
It is a white crystalline powder.
It is odourless and has bitter taste.
It is hygroscopic.
It is soluble in water, alcohol and chloroform.
Stability and Storage
It is affected by light and atmospheric oxygen. Hence, it should be stored in tightly closed light-resistant containers.
Uses
To treat myasthenia gravis.
To treat paralytic ileus.
To treat postoperative urinary retention.
Pharmaceutical formulations
Neostigmine tablet BP, IP.
Neostigmine injection BP, IP.
Brand Name
Prostigmine. Bloxiverz.
3 Give the structure, chemical name, properties, storage, uses, brand names, pharmaceutical formulations of acetylcholine. What do you mean by muscarinic and nicotinic actions of acetylcholine?
☞ Acetylcholine
Acetylcholine is an ester of choline with acetic acid.
It has two actions.
Muscarinic actions: These are produced by stimulation of muscarinic receptors, which are similar to mushroom alkaloid muscarine.
Cardiac inhibition.
Peripheral vasodilation.
Constriction of pupil.
Increase salivary secretion.
Constriction of smooth muscles of GIT and urinary bladder.
Nicotinic actions: These are produced by stimulation of nicotinic receptors which are similar to nicotine alkaloid from tobacco.
Stimulation of skeletal muscle.
Acetylcholine
Properties
It is a small, polar, hydrophillic compound with the delique-scent liquid.
It is soluble in ethanol.
It is insoluble in diethyl ether and chloroform.
It is a choline molecule that has been acetylated at the oxygen atom.
Stability and storage
Acetylcholine is hygroscopic in nature. Acetylcholine solution is stored at 25°C and is stable for about 28 days. At a temperature of 50°C, acetylcholine showed a rapid breakdown after 1 day.
Uses
It is used as miotic (during ophthalmic surgery).
Acetylcholine is a direct acting parasympathomimetic.
It is a naturally occurring neurohormone that helps to transmit nerve impulses at all cholinergic sites including somatic and autonomic nerves.
Acetylcholine is used to give signal to muscle movement.
It is intended for intraocular use.
It contracts the smooth muscles, dilates the blood vessels, increases bodily secretions and slows heart rate.
Pharmaceutical formulations
Acetylcholine eye drops.
Acetylcholine powder for injection.
Acetylcholine gel.
Acetylcholine syrup.
Acetylcholine lozenges.
Acetylcholine strips.
Brand Names
Miochol E, N-Acetylcysteine, Mucomyst.
4 Write a note on following cholinergic drugs: (a) Carbachol, (b) Pilocarpine, (c) Edrophonium, (d) Tacrine hydrochloride, (e) Pralidoxime chloride, (f) Echothiophate iodide.
☞ (a) Carbachol
Properties
It occurs as a prismatic crystal of an ammonium salt and car-bomate ester.
It is soluble in ethanol, methanol, and dimethyl sulfoxide (DMSO).
It is insoluble in acetone, chloroform and ether.
It is a quaternary ammonium chloride and shows the muscarinic and nicotinic actions.
Stability and storage
It should be stored in a refrigeration at a temperature of 4°C. The stock solutions are stable for up to 6 months at 4°C.
Uses
It is a cholinergic agent.
It induces miosis.
Used in treatment of glaucoma.
Carbachol is also used to stimulate micturition.
Pharmaceutical formulations
Carbachol ophthalmic solutions/drops.
Carbachol ointments.
Brand Names
Carbastat, Carboptic, Miostat, Isopto.
Pilocarpine
It is an alkaloid obtained from dried leaves of pilocarpus species.
Properties
It occurs as colourless crystals or white crystalline particles.
It is odourless and has faintly bitter taste.
It is hygroscopic.
It is very soluble in water.
Stability and Storage
It is hygroscopic and affected by light; hence it is stored in tightly closed light-resistant containers.
Uses
It is used:
As a miotic.
To reduce intraocular pressure in glaucoma.
For accommodation of near vision of eye.
To counteract anticholinergic side effects.
Pharmaceutical formulations
Pilocarpine eye drops BP.
Pilocarpine HCl BP.
Pilocarpine tablet.
Pilocarpine ointment.
Trade Name
Pilocar, Opthocarpine, Salagen.
Edrophonium chloride
Properties
It is a crystalline solid.
It is bitter in taste.
It is fully soluble in water and alcohol.
It has rapid onset of action.
Stability and storage
It should be stored at controlled room temperature of range 15°–30°C.
Uses
Used as an antidote for over dose of d-tubocurarine.
It is a specific anti-curare agent.
It stimulates sketetal muscles.
It brings about rapid increase in muscle strength.
Pharmaceutical formulations
Edrophonium injection.
Edrophonium ointment.
Brand Names
Tensilon, Reversol, Enlon.
Tacrine hydrochloride
Properties
It occurs as a white solid crystal.
It is freely soluble in distilled water, 0.1 N HCl.
It is a pale yellow crystal known chemically as 1, 2, 3, 4-tetra-hydro-9acridinamine monohydrochloride monohydrate.
Stability and storage
It should be stored at a temperature of 20°–25°C and protected from moisture.
Uses
Used in Alzheimer’s disease.
Used in patient with dementia to improve memory, thinking and reasoning.
Used to increase the level of acetylcholine in the brain.
Pharmaceutical formulations
Tacrine hydrochloride tablet.
Tacrine hydrochloride capsule.
Brand Names
Cognex.
Pralidoxime chloride
Properties
It coccurs as a white crystalline non-hygroscopic powder.
It is freely soluble in water.
It is a quaternary ammonium compound.
Stability and storage
It shoule be stored under controlled room temperature of 15°–30°C.
Uses
Used as an antidote for poisoning of parathion and related pesticides.
As an effective antagonist for carbamates.
Used to treat muscle disorders.
Pharmaceutical formulations
Pralidoxime tablet
Pralidoxime injection.
Brand Names
Toxipam, Aldopam, Clopam, Neopam, 2-PamI.
Echothiophate Iodide
Properties
It occurs as a white, crystalline, hygroscopic solid.
It is a quaternary ammonium salt.
It is soluble in water and dehydrated alcohol.
Its aqueous solution have a pH of about 4.
Stability and storage
It is stable at room temperature for about 1 month. It should be kept away from light and moisture. It should be stored in refrigerator at 2°–8°C.
Uses
Used in the treatment of glaucoma.
In ophthalmic used to treat open angle glaucoma.
Used to treat certain eye focusing disorder.
Pharmaceutical formulations
Echothiophate eye drops.
Echothiophate eye ointment.
Brand Names
Phospholine iodide.
Cholinergic Blocking Agents/Anti-cholinergics/Parasympatholytics
D
1 What are anticholinergics? Classify anticholinergics with examples.
☞ Anticholinergics
The drugs which block the actions produced by stimulation of parasympathetic nervous system are called anticholinergics.
Classification
On Chemical basis and Origin:
Natural alkaloids, e.g. atropine, hyoscine (scopolamine)
Semisynthetic derivative, e.g. homatropine, ipratropium bromide.
Synthetic compounds:
Amino alcohol esters, e.g. tropicamide, cyclopentolate hydrochloride, clindinium bromide, dicyclomine hydrochloride, glycopyrrolate, propantheline bromide, meth-antheline bromide.
Amino alkyl ethers, e.g. benztropine mesylate, orphenad-rine citrate.
Amino alcohols, e.g. biperidine hydrochloride, procycli-dine hydrochloride, tridihexethyl chloride.
Amino amides, e.g. isopropamide iodide.
Miscellaneous, e.g. ethopropazine.
2 Write a note on ‘Atropine.’
☞ Atropine (natural alkaloid obtained from Atropa belladonna)
Structure
1 2
8 N CH3
3
O CH2OH
7
O C CH
6
5 4
Chemical Name
(1R, 3R, 5S) tropan 3yl (±) tropate
Properties
It occurs as a colourless crystal.
It has a bitter taste.
It is sparingly soluble in water.
It is freely soluble in chloroform.
Stability and Storage
It is affected by light. Hence it is stored in tightly closed light resistant containers.
Uses
As antispasmodic.
In peptic ulcer.
In biliary colic.
As a preanaesthetic medication.
In parkinsonism.
As a mydriatic.
To treat sialorrhoea.
To treat insecticidal poisoning.
Preparations
Atropine sulphate tablet.
Atropine eye ointment.
Atropine sulphate injection.
Morphine and atropine injection.
Atropine methonitrate BP, IP.
Compound adrenaline and atropine spray BP.
Brand Names
Lomoten, Lomotil, Eumydrin, Atrocin, Atrisolon, Atron, Atrosulph.
3 Give the structure chemical name, properties, uses, stability storage and uses and dicyclomine hydrochloride.
☞ Dicyclomine Hydrochloride
Structure
Chemical Name
2-(diethylamino)ethyl bicyclohexyl1carboxylate hydrochloride.
Properties
It occurs as a white crystalline powder with bitter taste.
It is soluble in water and chloroform.
Dicyclomine is a muscarinic receptor antagonist.
It is freely soluble in ethanol.
It is practically insoluble in ether.
Stability and storage
It should be stored at room temperature between 15°C and 30°C and kept away from light.
Uses
It is used as antimuscarinic and a non-specific antispasmodic agent (spasmolytic).
It is used in dysmenorrhoea, pylorospasm and biliary dysfunction.
It is used in motion sickness.
Used for treatment of functional bowel disorder and irritable bowel syndrome.
Pharmaceutical formulations
Dicyclomine tablet.
Dicyclomine capsule.
Dicyclomine injection.
Dicyclomine oral solution.
Brand Names
Meftal Spas, Spasil, Cyclospas-D, Cyclopam, Colimex, Diclospas, Colirid.
Dose
30 to 60 mg daily in divided doses.
4 Give details of following Anticholinergic drugs:
(a) Ipratropium bromide, (b) Tropicamide, (c) Cyclopentolate hydrochloride, (d) Clidinium bromide.
☞ (a) Ipratropium Bromide
Properties
It is a white or almost white crystalline powder.
It is tastless and odourless.
It is a quaternary ammonium derivative.
It is freely soluble in water and ethanol.
It is insoluble in chloroform and ether.
Stability and storage
It should be stored in the foil pouch and protected from light and moisture.
Uses
It is used in the treatment of acute asthmatic attack.
It is a bronchodilator.
It is used for the symptomatic relief of rhinorrhoea.
It inhibits ACh-enhanced release of chemical mediators.
It is used for the treatment of sialorrhoea.
Pharmaceutical formulations
Ipratropium bromide aerosol.
Ipratropium bromide spray.
Ipratropium bromide capsule.
Ipratropium bromide solution.
Brand Names
Impravent, Tropum, Duolin, Iprex, Combivent, Tiova.
Dose
40–80 mg by inhalation.
Tropicamide
Properties
It is a white or almost white crystalline powder.
It is odourless.
It is soluble in alcohol and methylene chloride but slightly soluble in water.
It is freely soluble in chloroform and solutions of strong acids.
Stability and storage
It should be stored in well-closed container and stored below 25°C. It should be protected from light and stored in sealed, conical-shaped container fitted with a twist and pull-off cap.
Uses
It is used to induce mydriasis and cycloplegia for ophthalmos-copy.
For the treatment of acute iritis, iridocyclitis, and keratitis.
Pharmaceutical formulations
Tropicamide eye drops.
Brand Names
Tropicamet, Tropac-P, Eytrop, Alcon, Tromide, Optimide, Mydriacyl.
Cyclopentolate Hydrochloride
Properties
It occurs as a white crystalline powder.
It is odourless.
It is soluble in water, methanol and ethanol.
It insoluble in toluene.
Stability and storage
It should be stored in a tightly closed container protected from light.
Uses
It is used to produce cycloplegia and mydriasis.
It is an anticholinergic agent.
In the management of iritis.
In iridocyclitis.
In keratitis and choroiditis.
To treat cycloplegic refraction.
Pharmaceutical formulations
Cyclopentolate hydrochloride eye drops.
Cyclopentolate hydrochloride solutions.
Brand Names
Pentolate, Cyclopan, Tropexp, Cyclopent, Cyclogyl, Cyclomid, AK-Pentolate, Cyclomydril.
Clindinium Bromide
Properties
It occurs as a white or nearly white crystalline powder.
It is odourless.
It is optically inactive.
Stability and storage
It should be stored in tightly closed container, in cool and well ventilated place at room temperature and kept away from light and children.
Uses
In the treatment of peptic ulcer.
In the treatment of hyperchlorhydria.
In ulcerative or spastic colon.
In anxiety states.
Used as bronchodialator in asthmatic conditions.
To relieve abdominal or stomach spasms.
Used in diverticulitis.
Used to treat irritable bowel syndrome.
Pharmaceutical formulations
Clindinium tablet.
Clindinium capsule.
Brand Names
Colinom, Clipoxt, Cibis, Spasril, Chlorax, Vasorex, Libtrax, QIBS.
System/CVS Agents
A Anti-Arrhythmic Agents
B Antihypertensive Agents
C Antianginal Agents (Vasodilators)
Anti-Arrhythmic Agents
A
1 Define and classify cardiovascular agents with suitable
examples.
The drugs which are used to treat various cardiovascular disorders are known as CVS agents.
☞ Classification of CVS Agents
Cardiotonics (cardiac glycosides), e.g. digoxin, digitoxin, gito-xin, ouabain, Lanatoside C.
Antiarrhythmic agents, e.g. quinidine, procainamide, propranolol, verapamil.
Antianginal agents (vasodilators), e.g. glyceryl trinitrate, ethyl nitrate, amyl nitrite, tolazoline, isosorbide dinitrate, pentaeryth-ritol, sodium nitroprusside.
Antihypertensive drugs, e.g. methyl dopa, guanethidine, reserpine, clonidine, hydralazine, nifedipine, mecamylamine, captopril, enalapril.
Lipid lowering agents (antihyperlipidaemic agents), e.g. clofi-brate, nicotinic acid.
Other drugs :
Diuretics, e.g. frusemide, hydroclorthiazide.
Anticoagulants, e.g. warfarin, dicoumarol.
2 What is Arrhythmia/Cardiac arrhythmia ? Define and classify anti-arrhythmic agents.
☞ Arrhythmia/Cardiac arrhythmia
It means disturbance in cardiac rhythm or heart beat. Arrhythmia can be caused by disturbance in conduction of impulse throughout the myocardium of heart.
Types of Arrhythmias
Tachycardia: Heart rate above 100 beats per minute.
Bradycardia: Heart rate lower than 60 beats per minute.
Atrial fibrillation.
Atrial flutter.
Ventricular flutter.
Extra systole.
Symptoms of Arrhythmia
Fatigue
Dizziness
Fainting
Rapid heart beat
Shortness of breath
Chest pain
Anxiety
☞ Anti-arrhythmic Agents
The drugs which are used in the treatment of cardiac arrhythmias are called anti-arrhythmic agents.
Classification
Membrane stabilising agent, e.g. quinidine, procainamide.
b-adrenergic blockers, e.g. propranolol, practolol.
Calcium channel blockers, e.g. verapamil, nifedipine.
The drugs that prolong duration of action potential, e.g. bretyli-um.
3 Write a note on quinidine as anti-arrhythmic agent.
☞ Quinidine
Properties
It occurs as white needle-like crystals.
It is odourless and has bitter taste.
It is sparingly soluble in water but soluble in alcohol.
It is dextrorotatory.
Stability and Storage
It darkens on exposure to light and hence it is stored in tightly closed light-resistant container.
Uses
For treatment of ventricular tachycardia.
Cardiac arrhythmia.
Extrasystolic atrial tachycardia.
In thyrotoxicosis.
To treat malaria
To maintain sinus rhythm. Pharmaceutical formulation Quinidine tablet.
Brand Name
Phenipam, Natcardine, Cardioquin, Quinaglute, Quinalan.
Dose
100 to 200 mg thrice daily.
4 Give the details of phenytoin as an anti-arrhythmic drug.
☞ Phenytoin (Dilantin)
Phenytoin is a hydantoin derivative (imidazolidine 2,4-dione)
Structure:
Chemical Name:
5,5-diphenyl imidazolidine 2,4dione, OR 5,5-diphenyl hydantoin.
Properties:
It is a white crystalline powder and is odourless.
It is very slightly soluble in water.
It is slightly hygroscopic.
Stability and Storage
It should be stored in a tightly-closed containers protected from light.
Uses
It is used for the treatment of refractory ventricular arrhythmia.
It is useful for prevention of tonic–clonic seizures.
To control status epileticus
To treat myotonia
To treat trigeminal neuralgia
To treat migraine
Used as an anti-arrhythmic agent
Pharmaceutical Formulations:
Phenytoin tablet
Phenytoin capsule
Phenytoin injection
Phenytoin oral suspension
Phenytoin and phenobarbitone tablets
Brand Names
Dilantin, Eptoin, Epileptin, Garoin, Phenytek.
5 Give the details of following anti-arrhythmic drugs.
(a) Procainamide hydrochloride, (b) verapamil, (c) Lidocaine, (d) Lorcainide hydrochloride, (e) Amiodarone
(f) sotalol.
☞ Procainamide Hydrochloride
Properties
It occurs as a white or yellowish-white crystalline powder which odourless and hygroscopic.
It is very soluble in water and freely soluble in alcohol.
Stability and Storage
It is stable in air but is hygroscopic hence it is stored in tightly closed
container.
Uses
For the treatment and prevention of:
Ventricular tachycardia.
Cardiac arrhythmia.
Atrial tachycardia.
To maintain sinus rhythm.
In thyrotoxicosis.
To maintain sinus rhythm.
Pharmaceutical Formulations
Procainamide HCl BP, IP.
Procainamide injection BP, IP.
Procainamide tablet BP.
Brand Name
Pronestyl, Procan, Procanbid.
Verapamil Hydrochloride
Verapamil is a calcium channel blocker.
Properties:
It occurs as a white crystalline powder.
It is soluble in organic solvents like ethanol.
It is odourless and has bitter taste.
It is soluble in water.
Stability and Storage
It should be stored at controlled room temperature and protected from light and freezing.
Uses
It is a calcium channel blocker used as anti-arrhythmic agent.
It is also used to treat hypertension
It is used for controlling ventricular rate in supraventricular tachycardia.
To control ventricular rate in patients with atrial fibrillation and flutter.
Pharmaceutical Formulations:
Verapamil tablet.
Verapamil capsule.
Verapamil injection IP
Verapamil solution
Brand Names
Isoptin, Verelan, Covera, Calan, Cardilox.
Lidocaine Hydrochloride (Lignocaine/Xylocaine)
Chemically it is an amide type of local anaesthetic
Properties
It is a white or creamy-white powder.
It is odourless.
It is practically insoluble in water.
It is very slightly soluble in alcohol but freely soluble in chloroform.
Storage
It is stored in tightly closed containers.
Uses
It is mainly used for its local anaesthetic activity.
It is used for:
Topical use.
Infiltration anaesthesia.
To produce dental analgesia.
For nerve block.
It is also used for treatment of cardiac arrhythmia.
Pharmaceutical formulations
Lignocaine injection.
Lignocaine eye drops.
Lignocaine gel.
Brand Names
Xylocaine, Otek, Otosil-C, Trox, Lidoject, Zingo, Kebutacaine.
Lorcainide Hydrochloride
Properties:
It is hydrochloride salt.
It is soluble in water, ethanol and DMSO..
Chemically, it is an acetamide derivative.
Stability and Storage
It should be stored in tightly closed container and kept under dry and dark place.
Uses
As an anti-arrhythmic agent
To treat ventricular arrhythmias
It has local anaesthetic activity
It helps to restore normal heart rhythm and conduction in patients with premature ventricular contraction, ventricular tachycardia and Wolff-ParkinsonWhite syndrome.
Pharmaceutical Formulations:
Lorcainide HCI tablet.
Lorcainide HCI injection.
Lorcainide HCI solution.
Brand Names
Remivox, Lorivox.
Amiodarone Hydrochloride
It is a potassium channel blocker and is class III anti-arrhythmic drug.
Properties:
It is white to slightly yellow crystalline powder.
It is slightly soluble in water.
It is freely soluble in dichloromethane.
It is soluble in methanol.
It is sparingly soluble in ethanol and very slightly soluble in
water.
It is a benzofuran derivative.
Stability and Storage
It should be stored in a tightly closed container and protected from light at a temperature not exceeding 30°C.
Uses
It is a potent anti-arrhythmic agent.
Used to treat atrial fibrillation, supraventricular tachycardia, recurrent ventricular fibrillation.
To treat recurrent hemodynamically unstable ventricular tachycardia.
Pharmaceutical Formulations:
Amiodarone tablet IP
Amiodarone injection
Amiodarone solution
Amiodarone liquid
Amiodarone IV infusion IP
Brand Names
Aldarone, Nexterone, Pacerone, Cordarone.
Sotalol Hydrochloride
It is a b-adrenergic blocker (antagonist). It is a class III antiarrhythmic drug.
Properties
It is a white cystalline powder.
It is freely soluble in water.
It is available as sotalol hydrochloride.
Stability and Storage
It should be stored in a tightly closed container at room temperature, away from excess heat and moisture.
Uses
It is a anti-arrhythmic agent
It is used for the treatment of both atrial and ventricular arrhythmias.
Pharmaceutical Formulations:
Sotalol tablet
Sotalol injection
Sotalol solution
Brand Names
Sotagard, Betapace, Sotacor, Sorine, Sotylize.
Dose
160–480 mg per day.
Antihypertensive Agents
B
1 What is Hypertension? Give the causes, symptoms and drugs used in hypertension.
☞ Hypertension
The WHO defined hypertension in adult as “a systolic pressure equal to or greater than 160 mm Hg and a diastolic pressure equal to or greater than 95 mm Hg.”
Hypertension means high systemic blood pressure due to defect in the haemodynamic function.
Types of Hypertension
Primary Hypertension (essential hypertension):
Here the exact cause is not known. But there is generally narrowing of blood vessels. It may be benign hypertension or malignant hypertension.
Secondary Hypertension:
It may be caused due to secondary disorders like renal disorders, endocrine disorders or toxaemia of pregnancy
Causes/Reasons of Hypertension:
Obesity, aging, modern lifestyles, stress, high alcohol intake, high salt intake, fatty diet as well as secondary reasons.
Symptoms of Hypertension:
Headache, fatigue, vision problems, chest pain, difficulty in breathing, irregular heart beats.
Drugs used in Hypertension:
Propranolol, Captopril, Ramipril, Methyldopate, Clonidine, Nifedipine
Types of Hypertension:
Types of Hypertensions
Pressure range (systolic/diastolic BP in mm Hg)
Normal Borderline Mild Moderate Severe
120/75–80
140/90–95
140–160/95–105
>140/105–120
>140/>120
2 Define and classify Antihypertensive drugs with
examples.
☞ Antihypertensives
The drugs which reduce elevated blood pressure to normal level are called antihypertensives.
☞ Classification
Centrally acting, e.g. clonidine, a-methyldopa.
Catecholamine depleter, e.g. reserpine.
Adrenergic receptor blockers, e.g. propranolol, metoprolol.
Adrenergic neuron blocker, e.g. guanethidine.
Ganglionic blockers, e.g. mecamylamine.
Diuretics, e.g. chlorthiazide, frusemide.
Calcium channel blockers, e.g. verapamil.
Vasodialators, e.g. hydralazine.
Angiotensin converting enzyme inhibitors, e.g. captopril, enalepril.
Aldosterone antagonists, e.g. spironolactone.
3 What are the properties of an ideal antihypertensive
agent.
☞ The Properties of an Ideal Antihypertensive Agent:
It should cause gradual blood pressure lowering in all body positions.
It should lower precapillary resistance without decreasing cardiac output.
It should be absorbed orally.
It should have slow detoxication to improve efficiency.
It should be effective in considerable low dose so as to avoid side effects like nausea, diarrhoea, constipation, headaches etc.
It should not produce tachycardia or postural hypotension.
Tolerance should not be developed with chronic administration.
4 Describe ‘Propranolol’ as an Antihypertensive Agent.
☞ Propranolol: It is a beta-adrenergic blocker.
Structure:
Chemical Name:
1-isopropyl amino,3(1naphthyloxy) propan2ol
Properties
It is a white powder.
It is odourless and has bitter taste.
It is soluble in water.
Stability and Storage
It is affected by light and hence it is stored in a well-closed light-
resistant container.
Uses
It is used to treat:
Cardiac arrhythmia.
Angina pectoris.
Arterial hypertension.
Hyperthyroidism in children.
Symptoms of anxiety.
Pharmaceutical Formulations:
Propranolol tablet.
Propranolol injection.
Brand Names
Inderal, Ciplar, Innopran XL, Hemangeol.
5 Give the structure, chemical name, properties, uses, stability storage, pharmaceutical formulation, brand names of captopril.
☞ Captopril:
It is an angiotensin converting enzyme inhibitor.
Structure:
Chemical Name:
1-[(2S)3mercapto2methyl1oxopropionyl] praline.
Properties:
It occurs as a white crystalline powder.
It has a slight sulphur like odour.
It is freely soluble in water and alcohol.
It melts at 88°C which resolidify and melts again at about 105°C.
Stability and Storage
It should be stored in a tightly closed container under cool and dry place at room temperature and should be kept away from light and moisture.
Uses
It is used to treat high blood pressure and congestive heart failure.
It is used to treat renal hypertension.
It is used to treat diabetic proteinuria.
It also improve the mood of depressed patient.
Pharmaceutical Formulations:
Captopril tablets IP.
Brand Names
Captoril, Capoten, Aceten.
6 Give the details of following Antihypertensive agents.
(a) Ramipril, (b) Methyldopate Hydrochloride, (c)
Clonidine Hydrochloride, (d) Hydralazine Hydrochlorde,
(e) Nifedipine.
☞ (a) Ramipril
Ramipril is an ACE inhibitor.
Ramipril is a prodrug of ramiprilate.
Ramiprilate is the active metabolite of ramipril.
Properties:
It is a white crystalline powder.
It is sparingly soluble in water.
It is freely soluble in polar organic solvents.
It melts between temperature 105°C and 112°C.
Stability and Storage
It should be stored in tightly closed container, protected from light and moisture.
Uses
In treatment of hypertension (antihypertensive)
In heart failure.
In treatment of myocardial infarction.
To prevent heart strokes.
To treat kidney problems.
It helps in relaxation of blood vessels.
Pharmaceutical Formulations:
Ramipril tablet IP.
Ramipril capsule IP.
Brand Names
Altace, Ramipril, Corpril, R Pril, Tritace, Cardace.
Dose
1.25 to 10 mg per day.
Methyldopate Hydrochloride (a-methyl dopa):
It is a central acting a-2adrenergic agonist.
It is a salt form of methyldopa.
Methyldopa is a prodrug which is metabolized in the CNS.
Properties:
It is a white crystalline powder.
It is freely soluble in water.
It is very soluble in dil. HCI.
Stability and Storage
It should be stored in a tightly closed light resistant container. It becomes brownish yellow colour when exposed to moisture or water.
Uses
Antihypertensive agent
To treat hypertension in pregnancy
To control primary hypertension
To reduce hot flushes in postmenopausal women
To treat pheochromocytoma
Pharmaceutical Formulations:
Methyldopate hydrochloride tablet.
Methyldopate hydrochloride capsule.
Brand Names
Aldepa, Emdepa, Almet, Dopagyt, Meldopa
Clonidine Hydrochloride
It is a central acting alpha adrenergic agonist
Properties:
It is a white to off-white crystalline powder.
It is odourless with bitter taste.
It is soluble in water.
It is stable in light, air and heat.
Stability and Storage
It should be stored in tightly closed containers.
Uses
As antihypertensive agent
To treat primary hypertension
In prevention of migraine
To treat dysmenorrhoea
To treat postmenopausal Vasomotor instability.
It is a vasodialator.
It is used for the management of opiate addiction.
Pharmaceutical Formulations:
Clonidine tablet IP.
Clonidine injection IP.
Clonidine hydrochloride and chlorthalidone tablet IP
Brand Names
Catapres, Arkamine, Hyperdine, Kapvay, Nexiclon, Jenlaga.
Hydralazine Hydrochloride
It is a peripheral vasodilator.
Properties:
It occurs as a white crystalline powder.
It is odourless and has a bitter saline taste.
It is soluble in water but slightly soluble in alcohol.
It is a hydrazinophthalazine derivative.
Stability and Storage
It should be stored in a tightly closed containers protected from light, at a temperature not exceeding 30°C.
Uses
As an antihypertensive agent.
In the management of essential hypertension.
To control hypertensive emergencies.
To improve congestive heart failures
Pharmaceutical Formulations:
Hydralazine tablet.
Hydralazine injection IP.
Brand Names
Alazine, Corbetazine, Aresoline, Mepresol, Hyperazine.
Nifedipine
It is a calcium channel blocker.
It is a 1,4-dihydropyridine derivative.
Properties:
It occurs as a white crystalline powder.
It is odours and tasteless.
It is insoluble in water.
It is slightly soluble in alcohol.
Stability and Storage
It should be stored in tightly-closed container protected from light.
Uses
As an antihypertensive agent
It is used to prevent chest pain caused by angina.
Used in ischaemic heart disease and myocardial infarctions.
Used in arteriosclerosis, Raynaud’s syndrome.
It is used to treat excercise induced asthma.
Pharmaceutical Formulations:
Nifedipine tablet IP.
Nifedipine prolonged release tablets IP.
Nifedipine capsules IP.
Nifedipine prolonged release capsules IP.
Brand Names
Nifediac, Nicardia, Nefedin, Myogard, Procardia, Afeditab, Adalat,
Calciguard.
Antianginal Agents (Vasodilators)
C
1 What is angina pectoris? Mention the drugs used in treatment of angina pectoris.
☞ Angina Pectoris
Angina pectoris is a heart disease in which there is a paroxysmal pains in the chest, usually due to interference with the supply of oxygen to the heart muscle and precipitated by excitement.
Angina pectoris refers to the chest pain towards left arm shoulder due to less supply or more demand of oxygen.
Angina is due to imbalance between myocardial oxygen requirement and oxygen supply.
Signs and Symptoms:
Chest pains, shortness of breath, sweating, fainting
Drugs used in Angina pectoris:
Isosorbide dinitrate, glyceryl trinitrate, propranolol, verapamil, nifedipine, amlodipine, diltiazem.
2 Define and classify antianginal drugs/vasodilators with
examples.
☞ Antianginals/Vasodilators:
The drugs are used in the treatment of angina pectoris by dilating the blood vessels are called antianginals or vasodilators.
☞ Classification of Antianginals/Vasodilators:
On the Basis of Mode of Action:
Nitrates, e.g. glyceryl trinitrate, isosorbide dinitrate.
B-blockers, e.g. propranolol, metoprolol, atenolol.
Calcium channel blockers, e.g. verapamil, diltiazem, nifedipine, amlodipine.
Potassium channel opener, e.g. nicorandil.
Peripheral vasodialators, e.g. tolazoline.
Coronary vasodialators, e.g. glyceryl trinitrate, ethyl nitrite, amyl nitrate.
3 Give the details of “Isosorbide dinitrate” as an
antianginal agent.
☞ Isosorbide dinitrate:
It is a vasodilator.
Properties:
It is a white crystalline, colourless compound.
It is freely soluble in organic solvents such as acetone, alcohol
ether.
It is only sparingly soluble in water.
It is odourless.
Its melting point is 70°C.
Stability and Storage
It should be stored in tightly-closed container, protected from light.
Uses
For the prevention and treatment of angina due to coronary artery disease (CAD) and congestive heart failure (CHF)
It is an antianginal/vasodilator agent.
Pharmaceutical Formulations:
Isosorbide dinitrate tablet IP.
Isosorbide dinitrate capsule.
Dilute isosorbide dinitrate IP.
Brand Names
Sorbitrate, Cardicap, Isordil, Ditrate, Bidil, Olvisol, Anzidin.
Diuretics
1 Define and classify diuretics giving suitable examples.
“The drugs which increase rate of formation and excretion of urine are known as diuretics.”
Classification
Cyclic polynitrogen compounds.
Xanthine derivative, e.g. aminophylline, theophylline, caffeine.
Pteridine derivative, e.g. triameterene.
Pyrazine derivative, e.g. amiloride.
Organomercurials, e.g. mersalyl, mercaptomerin.
Sulphonamides
1,3,4-thiadiazole derivative, e.g. acetazolamide (carbonic anhydrase inhibitor).
Containing furan ring, e.g. frusemide.
Thiazides and chlorthiazides, e.g. hydrochlorothiazide, chloro-thiazide.
Steroidal aldosterone antagonist, e.g. spironolactone.
Phenoxy acetic acid derivative, e.g. ethacrynic acid.
Acidifying salts, e.g. ammonium chloride.
Water and osmotic agents, e.g. mannitol urea.
2 What do you mean by Low Ceiling and High Ceiling (Loop diuretics)? Give examples.
☞ (a) Low ceiling diuretics.
They have longer duration of action, medium potency and are useful in long-term therapy, e.g. chlorthiazide.
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(b) High ceiling diuretics (loop diuretics):
They have rapid onset but shorter duration of action. As they mainly act on ascending limb of loop of Henle, they are called as loop diuretics. They have high potency and produce intense diuresis, e.g. frusemide, ethacrynic acid.
3 Give the details of “frusemide/furosemide”/Loop diuretic.
☞ Frusemide (anthranilinc acid/furan derivative)
It is a high ceiling/loop diuretic.
Structure
H2NSO
Chemical Name
COOH
1
6
2
5
3
2
4
NH
Cl
CH2
O
4-chloro, N-furfuryl amino, 5-sulphamoyl anthranilic acid
or
4-chloro, 2-furfuryl amino, 5-sulphamoyl benzoic acid
Properties
It occurs as a white to slight yellow crystalline powder.
It is odourless and tasteless.
It is practically insoluble in water and ether.
Stability and Storage
It should be stored in a well tightly closed container and protected from light.
Uses
It is used as diuretic.
It is used for management of hypertension.
It is used to treat edema associated with congestive heart failure, cirrhosis of liver.
To treat renal disease.
Pharmaceutical Formations:
Frusemide BP, IP.
Frusemide injection BP, IP.
Frusemide tablet BP, IP.
Brand Names
Lasix, Salinex, Frusenex, salurex, Frisix, Tebemid.
4 Give the details of following diuretics: (a) Acetazolamide,
(b) Bumetanide, (c) Chlorthalidone, (d) Benzthiazide,
(e) Metolazone, (f) Xipamide and (g) Spironolactone.
☞ (a) Acetazolamide:
It is a carbonic anhydrase inhibitor.
Properties:
It is a white to faintly yellowish white crystalline powder.
It is odourless.
It is weakly acidic.
It is slightly soluble in water.
Stability and storage:
It should be in tightly closed container, protected from light and
moisture.
Uses:
It is used to reduce edema.
In the treatment glaucoma.
In the treatment of epilepsy and hypertension.
Used to treat acute mountain sickness.
To treat periodic paralysis.
Pharmaceutical formulations:
Acetazolamide tablet IP.
Acetazolamide extended release capsule.
Acetazolamide powder for solution.
Brand Names:
Diamox, Zolamide, Synomax, Iopar-SR, Acetazolam.
Dose:
Initial dose, 500 mg, subsequent doses, 250 mg every six hours.
Bumetanide:
It is a potent loop diuretic with a rapid onset and short duration of
action.
Properties:
It is a white crystalline powder.
It is soluble in acetone and in ethanol.
It is slightly soluble in dichloromethane.
It practically insoluble in water.
Stability and storage:
It is stored in airtight container and is protected from light.
Uses:
As a diuretic.
Used to reduce edema associated with CHF, liver and kidney
disease.
Pharmaceutical formulations:
Bumetanide injection IP.
Bumetanide oral solution IP.
Bumetanide tablets IP.
Brand Names:
Bumex, Burinex, Bumet.
Dose:
1–5 mg oral, 2–4 mg IM/IV
Chlorthalidone:
It is a long acting thiazide diuretic.
It is a sulfamoyl benzamide derivative.
Properties:
It is a white to yellowish white crystalline powder.
It is insoluble in water, ether and chloroform.
It is slightly soluble in alcohol and soluble in methanol.
It is soluble in alkali hydroxide solution.
Stability and storage:
It is stored in a tightly-closed container protected from light at controlled room temperature.
Uses:
As a diuretic.
Used to treat hypertension.
Used to treat edema associated with cardiac failure, liver failure and nephrotic syndrome.
It is effective in nephrogenic diabetes insipidus.
Pharmaceutical formulations:
Chlorthalidone tablets.
Brand Names:
Thalitone, Thalizide, Hygroton, Hythalton, Hydrazide.
Dose:
Intial dose is 15 mg once daily.
Benzthiazide:
It is a thiazide diuretic.
Properties:
It occurs as a fine white, crystalline powder.
It has characteristic odour with bitter taste.
It is practically insoluble in water.
It is soluble in alkaline solution.
Stability and storage:
It is stored in a tightly-closed container protected from light and air.
Uses:
As a diuretic.
Used for the treatment of hypertension and edema.
It is given in combination with potassium sparing diuretics.
It is used to prevent renal stone formation.
Pharmaceutical formulations:
Benzthiazide tablets.
Brand Names:
Edemax, Dihydrex, Exna, Aquatag.
Metolazone:
It is a thiazide like diuretic.
Metolazone is a quinazoline derivative.
Properties:
It occurs as a white crystalline powder.
It is odourless and tasteless.
It is sparingly soluble in water and alcohol.
It is insoluble in organic solvents such as ethanol, DMSO and dimethyl formamide (DMF).
Chemically it is quinazoline derivative.
Stability and storage:
It is a light sensitive drug, hence it is stored in a tight light resistant container and protected from moisture.
Uses:
As a diuretic.
For the treatment of congestive heart failure and high blood pressure.
Used along with loop diuretics such as furosemide or bumetanide.
For the treatment of edema.
Pharmaceutical formulations:
Metolazone tablets.
Brand Names:
Mykrox Metoz, Zaroxolyn, Zytanix.
Dose:
5–20 mg by oral route for the treatment of edema.
Xipamide:
It is a sulfonamide diuretic.
Properties:
It is a yellowish white crystalline powder.
It is odourless.
It is soluble in water and alcohol.
It is freely soluble in solutions of alkali hydroxides.
Stability and storage:
It is stored in an airtight container at room temperature.
Uses:
As a diuretic.
For the treatment of edema and hypertension.
Pharmaceutical formulations:
Xipamide tablet.
Brand Names:
Diurex, Diurexan, Aquophor, Aquaphoril.
Dose:
40 mg/day.
Spironolactone:
It is a potassium sparing diuretic.
It is an aldosterone receptor antagonist.
It is a weak diuretic.
Properties:
It occurs as light cream coloured crystalline powder with mer-captan like odour.
It is insoluble in water.
It is slightly soluble in methanol.
It is soluble in ethylacetate and ethanol.
It exibits polymorphism.
Stability and storage:
It is stored in tightly closed light resistant container.
Uses:
As a diuretic.
Used in the management and treatment or hypertension and heart failure.
Pharmaceutical formulations:
Spironolactone tablet IP.
Spironolactone suspension.
Spironolactone capsule.
Brand Names:
Aldactone, Aldactazide, Carospir.
Dose:
100 to 200 mg daily, in divided doses.
Agents/
Antidiabetic Agents
1 What is hypoglycemia? Write a note on diabetes mellitus. Mention the drugs used in diabetes mellitus.
☞ Hypoglycemia:
Hypoglycemia is a condition in which blood sugar (glucose) level is lower than normal.
Diabetes Mellitus:
Diabetes mellitus is a condition caused due to raised glucose concentration in the blood due to deficiency of insulin.
Diabetes is a group of diseases characterized by a state of
chronic hyperglycemia.
The hyposecretion of insulin from the b cells of islets of Lang-erhans leads to increased blood sugar level. The sugar passes through urine, the condition is called diabetes mellitus.
The “diabetes” means large volume of urine is passed. The term “mellitus” means sweet.
In diabete mellitus the blood glucose level exceeds normal renal threshold level (180/100 ml) hence glucose is found in the urine.
Types of Diabetes Mellitus:
Type 1. Insulin Dependent Diabetes Mellitus (IDDM):
It is also called Juvenile-onset diabetes mellitus.
It occurs in children and adolescents.
Type 2. Non-insulin Dependent Diabetes Mellitus (NIDDM):
It is also called maturity onset diabetes mellitus.
It develops in middle ages or in elderly patients who are often
obese.
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Type 3. Malnutrition-related diabetes mellitus (MRDM):
Type 4. Secondary diabetes:
It may be due to certain pancreatic disorders or genetic syndrome or
may be drug-induced.
Signs and Symptoms of Diabetes Mellitus:
Excessive thirst, excessive urination, fatigue, dryness of mouth,
weight loss.
Drugs Used in Diabetes Mellitus:
Insulin, glibenclamide, tolbutamide, phenformin, metformin, chlorpropamide.
2 What are hypoglycemic agents? Classify hypoglycemic agents with suitable examples.
☞ Hypoglycemic agents/antidiabetic agents:
The drugs which lower the blood sugar level and are used in the treatment of diabetes mellitus are known as hypoglycemic agents.
Classification
Hormones (parenteral): Insulin and its derivatives.
Oral hypoglycemic agents.
Sulphonyl urea derivatives, e.g. chlorpropamide, tolbutamide, glibenclamide.
Biguanide derivatives, e.g. phenformin, metformin.
Plant source, e.g. guar gum.
3 What is insulin? Give the storage, uses and official
preparations of insulin.
☞ Insulin
Insulin is a protein hormone secreted by b cells of the islets of Lang-erhans of pancreas.
Commercial source of insulin is the pancreas of ox and pig.
Properties
It is a white powder.
It is slightly soluble in water.
It dissolves in dilute solution of mineral acids.
It is also soluble in alkali hydroxides in which it is hydrolysed.
It is inactivated by proteolytic enzymes.
It is sensitive to heat and light.
Stability and Storage
It is sensitive to heat and light. Hence it should be stored in a temperature between 2°C and 8°C and should not be allowed to freeze. Insulin injection is stored in multidose container.
Uses
It is used:
To control diabetes mellitus.
To regulate carbohydrate metabolism.
To treat hyperkalemia.
To treat severe ketosis or diabetic coma.
Official Preparations of Insulin (Stable Preparations)
Insulin injection BP, IP
Neutral insulin injection BP.
Globin zinc insulin injection BP, IP.
Isophane insulin injection BP, IP.
Biphasic insulin injection BP.
Protamine zinc insulin injection BP, IP.
Insulin zinc suspension (crystalline) BP, IP.
Insulin zinc suspension BP, IP.
4 Give the details of following hypoglycemic agents: (1) Metformin and (2) Glibenclamide.
☞ 1. Metformin (biguanidine derivative):
It is a biguanidine derivative.
Structure:
CH3 H
| 1 |2 3
CH3—N—C—N—C—NH2 • HCl
|| ||
NH NH
Chemical Name:
1,1-dimethylbiguanidine hydrochloride.
Properties:
It is a white crystalline powder.
It is odourless and bitter in taste.
It is freely soluble in water.
It is insoluble in chloroform.
Stability and Storage:
It is a hygroscopic and hence it is stored in tightly-closed containers.
Uses:
As hypoglycemic agent.
Used as first-line medication for the treatment of type-2 diabetes.
To treat non-insulin dependent diabetes mellitus.
To treat insulin dependent diabetes mellitus in combination
with insulin.
To treat diabetes associated with hyperlipoproteinaemia.
Pharmaceutical formulations:
Metformin tablets IP.
Metformin oral solution IP.
Metformin hydrochloride prolong release tablet IP.
Brand Names:
Glucophage, Diabex, Fortamet, Glycomet, Diaformin, Glumetza,
Riomet.
Dose:
0.5 to 2.5 gm in divided doses.
Glibenclamide:
It is a sulphonyl urea derivative.
It is a second generation hypoglycemic agent.
It is also known as glyburide.
Structure:
Chemical Name:
5-chloro-N-[4-(cyclohexyl carbamoylsulfamoyl)phenyl]ethyl]-2-methoxy benzamide.
Properties:
It is a white crystalline powder.
It is odourless.
It is slightly soluble in water.
It is sparingly soluble in chloroform.
Stability and storage:
It is stored in tightly closed container protected from light.
Uses:
As a hypoglycemic agent.
To treat non-insulin dependent diabetes mellitus.
To treat type-2 diabetes.
Pharmaceutical formulations:
Glibenclamide tablet.
Brand Names:
Diabeta, Daonil, Euglucon, Betanase, Bionil, Afdiex.
Dose:
1–6 mg per day.
5 Give the properties, stability and storage, uses, formulations, brand names of following hypoglycemic agents. (a) Glimepiride (b) Pioglitazone, (c) Repaglinide,
(d) Gliflozins and (e) Gliptins.
☞ (a) Glimepiride:
It is a sulfonyl urea derivative.
It is a long acting third generation hypoglycemic agent.
Properties:
It a white powder.
It is soluble in dimethyl formamide.
It is sparingly soluble in dichloromethane.
It is slightly soluble in methanol.
It is practically insoluble in water.
Stability and storage:
It is stored in a cool, dry place at room temperature and kept away from light and moisture.
Uses:
Used for the treatment of type 2 diabetes.
Used with a proper diet and exercise to control high blood glucose level.
Pharmaceutical formulations:
Glimepiride tablet IP.
Brand Names:
Amaryl, Glypride, Glimer, Avandaryl, Duetact, Tandemact.
Dose:
1–6 mg per day.
Pioglitazone:
It is a thiazolidinedione derivatives.
It is also called insulin sensitizing agent.
Properties:
It is white crystalline powder.
It is odourless.
It is slightly soluble in anhydrous ethanol.
It is very slightly soluble in acetone and acetonitrile.
It is practically insoluble in water.
Stability and storage:
It is stored in well-closed containers protected from light and moisture.
Uses:
Used for the treatment of type 2 diabetes mellitus.
As a hypoglycemic agent.
Pharmaceutical formulations:
Pioglitazone tablets IP.
Pioglitazone hydrochloride tablets.
Brand Names:
Pionorm, Piorest, Bioglita, Diavista, Actos, Actoplus Met.
Repaglinide:
It is a meglitinide analogue.
It is a oral hypoglycemic agent.
It has a rapid onset and a short duration of action.
Properties:
It is a white to off-white crystalline powder.
It is odourless.
It is poorly water soluble.
Its melting point is 126°–128°C.
Stability and storage:
It is stored in an airtight container at room remperature between 15°C and 25°C and kept a way from light and moisture.
Uses:
Used as hypoglycemic agent.
To control high blood sugar level with a proper diet and exercise.
Pharmaceutical formulations:
Repaglinide tablet IP.
Brand Names:
Raplin, Prandin, Novonorm, Eurepa, Prandimet, Enyglid, Gluco-norm.
Dose:
1–8 mg daily.
Gliflozins:
Gliflozins are newly developed class of oral hypoglycemic
agents.
Gliflozins include canagliflozin, dapagliflozin and empagliflozin.
These are sodium-glucose co-transporter-2 (SGLT2) inhibitors.
Properties:
These are soluble in water.
Stability and storage:
It should be stored in a cool and dry place protected from light.
Uses
Used for the treatment of type 2 diabetes mellitus.
As a hypoglycemic agents.
Sometimes can be used along with insulin to treat type-1 diabetes.
Pharmaceutical Formulations
Canagliflozin tablet.
Dapagliflozin tablet.
Empagliflozin tablet.
Brand Names
Farxiga, Invokana, Qtern.
Dose:
5 mg orally once daily.
Gliptins
Gliptins are the new class of hypoglycemic agents.
Gliptins includes: Sitagliptin, Vildagliptin, Saxagliptin.
Properties
Sitagliptin is a white to off-white crystalline powder.
It is non-hygroscopic powder.
These drugs are soluble in water and organic solvents such as ethanol, DMSO and DMF.
Stability and Storage
These are stored in tightly closed container at 20–25°C
Uses:
As hypoglycemic agents.
Used as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Pharmaceutical Formulations
Sitagliptin tablet. Vildagliptin tablet. Saxagliptin tablet.
Brand Names
Eucreas, Galms, Janumet, Januvia, Xelevia.
Analgesic and
Agents
A Narcotic Analgesics (Opioid Analgesics)
B Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Introduction
Analgesics: The drugs which relieve the pains are called analgesics.
Antipyretics/Febrifuge: The drugs which reduce elevated body temperature to normal level are known as antipyretics,
e.g. paracetamol, analgin, phenacetin.
Anti-inflammatory: The drugs which reduce inflammation are known as anti-inflammatory agents.
Narcotic Analgesics/Opioid Analgesics: The drugs which reduce pain sensation along with loss of consciousness and sleep are known as narcotic analgesics, e.g. morphine, heroine, codeine, pethidine, methadone.
Inflammation: Inflammation is a complex biological response which occurs when the body is exposed to infective agents or to a physical or chemical injury.
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Narcotic Analgesics (Opioid Analgesics)
1 Define and classify Narcotic Analgesics with examples.
Mention the uses of Narcotic Analgesics.
☞ Narcotic Analgesics s
The drugs which produce narcosis along with analgesic effect are called narcotic analgesics.
☞ Classification
Naturally occuring:
Morphine and its analogues
e.g. morphine, codeine, hydromorphine, oxymorphine, diamorphine, ethylmorphine.
Synthetic drugs:
Morphanion analogues, e.g. levorphanol.
Benzomorphan analogues, e.g. pentazocin.
4-phenylpiperidine analogues, e.g. pethidine.
Phenyl propylamine analogues, e.g. methadone, dextrap-ropoxyphone.
☞ Uses of Narcotic Analgesics
To relieve moderate to severe pain.
To suppress non-productive cough (antitussive)
To induce sleep in the presence of pain.
To control diarrhoea.
2 Give the details of “Morphine” as Narcotic Analgesic.
☞ 1. Morphine
It is a principle alkaloid obtained from opium. It belongs to
phenanthrene class of alkaloids.
It was the first narcotic analgesic discovered.
☞ Properties
It occurs as white needle-like crystals.
It has bitter taste.
It is very slightly soluble in water.
It is levorotatory and is monophasic liquid.
It is practically insoluble in ether and chloroform.
The solution is sterilised by maintaining at 98–100°C for
30 minutes with bactericide or by filtration.
☞ Stability and Storage
It should be stored in a well-tight closed container and protected from light.
Uses
It is used:
As narcotic analgesic.
To treat diarrhoea.
To suppress cough.
As a pre-anaesthetic medication.
As a hypnotic when insomnia is due to pain.
To relieve anxiety due to pain.
To relieve pain in biliary colic.
To relieve pains associated with neoplastic diseases.
Pharmaceutical Formulations
Morphine injection IP.
Morphine and atropine injection.
Morphine and ammonium chloride mixtures.
Morphine and ipecacaunha mixture.
Morphine and kaolin mixture.
Morphine hydrochloride solution.
Morphine suppositories.
Brand Names
Zephrol, Duromorph, Astramorph, Morcontin.
Dose
10–50 mg oral/IM 2–3 mg by IV
3 Describe the following analogues of morphine.
(a) Codeine (b) Diamorphine (c) Methadone (d) Pentazocin (e) Pethidine
☞ (a) Codeine
It is an alkaloid obtained from opium.
Properties
It occurs as a white crystalline or colourless powder.
It is odourless and has bitter taste.
It is slightly soluble in water and freely soluble in alcohol.
It is very soluble in dilute acids.
Stability and Storage
It should be stored in a well tightly closed container and protected from light.
Uses
It is used:
As narcotic analgesic.
To suppress cough.
To treat diarrhoea.
As a sedative and hypnotics.
Also used in combination with aspirin.
Pharmaceutical Formulations
Codeine phosphate BP, IP.
Codeine linctus BP.
Codeine phosphate syrup IP.
Codeine phosphate tablet BP.
Codeine and aspirin tablet.
Aspirin, phenacetin codeine tablet BP.
Brand Names
Codlin, Cosaka, Kefex., Corex, Codistar, Glycodin, Powerin.
Dose
10–30 mg per day.
Diamorphine (Heroin)
It is diacetyl morphine.
It is commonly known as heroin.
Properties
It appears as white crystalline powder.
It is soluble in water and alcohol.
It is produced by acetylation of morphine.
Stability and Storage
It is stored in a tightly closed container at controlled room temperature and protected from light.
Uses
Used for the treatment of severe pain.
As a narcotic analgesic.
To treat severe pain associated with surgical procedures, myocardial infarction.
Pharmaceutical Formulations
Diamorphine hydrochloride tablet.
Diamorphine hydrochloride injection.
Diamorphine hydrochloride nasal spray.
Diamorphine hydrochloride powder for reconstitution.
Brand Names
Diagesil, Udidyne, Ayendi, Diaphin.
Methadone
It is a substitute of morphine.
Properties
It occurs as a white crystalline powder.
It is odourless and has a bitter taste.
It is soluble in water and freely soluble in alcohol.
Stability and Storage
It is stored in a well-closed container protected from moisture and light.
Uses
Used as morphine substitution.
To relieve moderate to severe pain.
For the management of opioid dependance.
To suppress cough.
Pharmaceutical formulations
Methadone tablets IP
Methadone oral solution IP
Methadone injection IP
Methadone linctus IP
Methadone hydrochloride oral concentrate IP
Brand Names
Dolophine, Methadose, Physeptone, Diskets.
Dose
2.5 to 10 mg oral/IM
Pentazocin
It is 2,6-methanobenzazocin derivative.
Properties
It is white or creamy white powder.
It is odourless and has slightly bitter taste.
It is very slightly soluble in water and soluble in alcohol.
Uses
It is used:
As narcotic analgesic.
As preanaesthetic medication.
As analgesic during labour pains.
Stability and Storage
It is stored in well-closed light-resistant container.
Pharmaceutical Formulations
Pentazocin tablet.
Pentazocin injection.
Pentazocin tablet BP.
Brand Names
Pentaron, Fortwin.
Pethidine
It is a piperidine derivative.
C6H5 4 COOCH2CH3
5 3
6 2
N 1
CH3
Ethyl, 1-methyl, 4-phenyl-piperidine 4-carboxylate
Properties
It is a white crystalline powder.
It is odourless and has bitter taste.
It is soluble in water, alcohol and chloroform.
Its solutions are sterilised by autoclaving or filtration.
Storage
It should be stored in a well tight closed container and protected from light.
Uses
It is used:
To relieve moderate to severe pains.
As preanaesthetic medication.
As analgesic during labour.
In treatment of morphine addiction as substitute.
Pharmaceutical Formulations
Pethidine tablet BP, IP.
Pethidine HCl injection BP, IP.
Brand Names
Pethilorfan, Dolantin.
4 What are Narcotic Antagonist? Explain any three Narcotic Antagonists.
☞ Narcotic Antagonists
Narcotic Antagonists are the drugs which block the euphoric effects of opiates by attaching to opiate receptors.
Narcotic antagonists are used as antidote to treat poisoning of
narcotic analgesics.
Examples: Naloxone, Nalorphine, Naltrexone.
Nalorphine
It was the first clinical useful narcotic antagonist.
It is a mixed opioid agonist–antagonist.
Nalorphine has less analgesic effect than morphine.
It is also known as N-allylnormorphine.
Properties
It is a white crystalline powder.
It is odourless.
It is insoluble in chloroform and ether.
It is soluble in dilute alkali hydroxide solution.
It is sterilized by autoclaving or by filtration.
Stability and Storage
It slowly darkens on prolonged exposure to light and air. Hence it is stored in a tightly closed container at controlled room temperature and protected from light.
Uses
As an antidote for morphine poisoning.
Used to reverse the opioid overdose.
Pharmaceutical Formulations
Nalorphine injection.
Dose
Usually administered IV in the dose of 3 to 5 mg repeatedly within half an hour, if necessary, (in morphine poisoning).
Brand Names
Nalline, Lethidrone.
Naloxone
It is a narcotic/opioid antagonist.
Properties
It occurs as a white crystalline powder.
It is freely soluble in water, dilute acids and strong alkali.
Stability and Storage
It is stored in a tightly closed container protected from light.
Uses
As a narcotic/opioid antagonist.
To block or reverse the effects of opioid drugs.
Antidote for acute morphine poisoning.
Pharmaceutical Formulations
Naloxone hydrochloride injection.
Dose
0.4 to 0.8 mg by IV repeated every 10 to 15 minutes in morphine poisoning.
Brand Names
Narcon, Evzio, Narcotan.
Naltrexone
It is a noroxymorphone derivative with competitive opioid antagonistic activity.
Properties
It is white crystalline compound.
It is very hygroscopic.
It is soluble in water.
Stability and Storage
It is stored at room temperature away from light and moisture.
Uses
It is used for the management of alcoholism and addiction to opioid drugs.
It is used to treat cholestatic pruritus.
It is used in obesity.
It is used to treat opioid dependance.
It is used to treat severe pains.
Pharmaceutical Formulations
Naltrexone hydrochloride tablet.
Naltrexone tablet IP.
Naltrexone implantable pellet.
Brand Names
Nalorex, Adepend, Antaxone, Celupan, Contrave, Embeda, Vivitrol,
Naltima, Revia.
Non-steroidal Anti-inflammatory
1 What are non-steroidal anti-inflammatory drugs (NSAIDs)? Classify NSAIDs with suitable examples. OR Classify analgesics and antipyretics giving examples.
☞ NSAIDs
These are the drugs which are used to relieve pain, reduce inflammation and also lower the elevated body temperature.
The NSAIDs act by inhibition of the cyclo-oxygenase (COX)
enzyme.
☞ Classification of NSAIDs
Salicylates, e.g. aspirin, sodium salicylate.
P-aminophenol derivatives, e.g. paracetamol, phenacetin.
Pyrazolone derivative, e.g. phenylbutazone, oxyphenbutazone
metamizole.
Indole acetic acid derivative, e.g. indomethacin, sulindac.
Phenylacetic acid derivative, e.g. diclofenac, aceclofenac.
Propionic acid denvative, e.g. ibuprofen, ketoprofen, fenopro-fen.
Oxicam derivatives, e.g. piroxicam, tenoxicam.
Selective COX-2 inhibitors, e.g. celecoxib, etoricoxib.
Anthranillic acid derivative, e.g. mefenamic acid.
2 Write a note on Aspirin. Describe the salicylic acid derivative used as anti-inflammatory agent.
☞ Aspirin (Acetylsalicylic Acid) [ASA]
Structure
O
3
2
1
6
O C CH3
4
5
COOH
Chemical Name
Ortho-acetoxy benzoic acid or 2-acetoxy benzoic acid
Properties:
It occurs a white crystalline powder.
It is colourless.
It is odourless and has slightly bitter taste.
It is soluble in water, freely soluble in alcohol.
Stability and Storage
It should be stored in a well tightly closed container and protected from light and kept in a cool, dry place.
Uses
It is used as analgesic to relieve moderate pains like headache,
toothache.
It is used as antipyretic.
It has an anti-inflammatory action and is used in the treatment of
rheumatoid arthritis.
It is used to treat gout.
In high doses, it is used to reduce risk of myocardial infarction.
Brand Names
Disprin, Aspro, Anacin, Coldarin, Powerin, Codopyrin, Ecosprin,
Zorprin, Asatab, Durlaza.
Pharmaceutical Formulations
Aspirin tablet BP, IP.
Soluble aspirin tablet.
Aspirin and caffeine tablet.
Dispersible aspirin and caffeine tablet.
Pediatric dispersible aspirin tablet BP.
Dispersible aspirin and codeine tablet BP.
Dose
0.5 to 2 gm per day.
3 Write a note on Ibuprofen. OR Give details of propionic acid derivative used as anti-inflammatory agent.
☞ Ibuprofen
It is a propionic acid derivative.
Structure
Chemical Name
(RS)-2-(4-isobutyl phenyl) propionic acid.
Properties:
It occurs as white crystals or white crystalline powder.
It has a characteristic odour.
It is very slightly soluble in water.
It is soluble in aqueous solution of alkali.
Storage
It is stored in a tightly closed container, protected from light and temperature.
Uses
It is used to treat:
Rheumatoid arthritis.
Osteoarthritis.
Dysmenorrhoea.
Neck pains.
Pains in malignant disease.
Dental pains.
Muscle aches.
Pharmaceutical Formulations
Ibuprofen tablet IP, BP.
Ibuprofen and paracetamol tablet. IP.
Ibuprofen cream I.P.
Brand Names
Brufen, Ibugesic plus, Alfam, Advil, Genpril, Ibular, Acifen, Em-flam.
4 Describe the details of paracetamol. OR Give the details of analgesic antipyretic drug which is a p-aminophenol derivative.
☞ Paracetamol (Acetaminophen)
It is a p-aminophenol derivative.
Structure
1
4
2 3
HO
NH.COCH3
6 5
Chemical Name
P-acetamido phenol OR 4-acetamido phenol OR P-hydroxy acetan-ilide.
Properties
It occurs as white crystals or white crystalline powder.
It is odourless and has bitter taste.
It is sparingly soluble in water.
It is insoluble in ether and chloroform.
Stability and Storage
It should be stored in a well tightly closed container and protected from light.
Uses
It is analgesic and antipyretic agent.
It is used to relieve the pain of headache, and other pains arising
from muscles and joints.
Brand Names
Crocin, Metacin, Calpol, Paramol, Albinol, Cipmol, Cofamol, Panadol.
Pharmaceutical Formulations
Paracetamol tablet IP, BP.
Paracetamol elixir.
Paracetamol oral suspension.
Paracetamol syrup.
Paediatric paracetamol elixir BP.
Acetaminophen tablet USP.
Acetaminophen elixir USP.
Dose
325–625 mg 3–4 times daily.
5 Give the properties, stability and storage, uses, pharmaceutical formulations, brand names of following NSAIDs.
(a) Diclofenac (b) Piroxicam (c) Celecoxib (d) Mefenamic acid (e) Aceclofenac.
☞ (a) Diclofenac
It is a phenylacetic acid derivative of non-selective COX inhibitor class.
It inhibits both COX-1 and COX-2.
Properties:
It is a white to slight yellowish crystalline powder.
It is a weak acid.
It is poorly soluble in water.
It is slightly hygroscopic.
It is freely soluble in methanol.
It is practically insoluble in ether in chloroform and in toluene.
Stability and Storage
It is stored in a well-closed container protected from moisture and light.
Uses
Used for the treatment of rheumatoid arthritis.
Used in the treatment of osteoarthritis and ankylosing spondylitis.
To treat postoperative ocular inflammation or ocular pain.
Used in toothache, dysmenorrhoea.
To treat gout.
To treat renal colic, post-traumatic and postoperative inflammatory conditions.
Pharmaceutical Formulations
Diclofenac prolong release tablets IP
Diclofenac gastro resistant tablet IP
Diclofenac gel IP
Diclofenac injection IP
Brand Names
Arthrotec, Diclonac, Movonac, Diclomax, Voltaren, Voveran, Volta-flam, Catatlam.
Dose
Orally or by intramuscular injection, 25 to 75 mg.
Piroxicam
It is oxicam derivative of non-selective COX inhibitor class.
It works by preventing the production of prostaglandins which are involved in the mediation of pain, stiffness, tenderness and swelling.
Properties:
It is a white or slightly yellow odourless powder.
It is poorly soluble in water.
It is soluble in organic solvents such as DMSO and dimethyl formamide.
Stability and Storage
It is stored in a well-closed container under dry place and is kept away from light, heat and moisture.
Uses
As analgesic antipyretic.
As antinflammatory in rheumatoid arthritis.
In the treatment of gout.
Used in treatment of musculoskeletal injuries.
Used in dentistry.
Pharmaceutical Formulations
Piroxicam tablet IP
Piroxicam capsule IP
Piroxicam injection.
Piroxicam gel.
Brand Names
Pirox, Piricam, Minicam, Dalonex, Axicam, Feldene.
Dose
10 to 20 mg daily.
Celecoxib
It is a selective COX-2 inhibitor.
It is a diaryl substituted pyrazole derivative.
Properties
It is off-white to pale yellow powder.
It is practically insoluble in water.
It is soluble in organic solvents such as ethanol, DMSO and dimethyl formamide.
Stability and Storage
It is stored at room temperature and is kept away from light and moisture.
Uses
It has analgesic, antipyretic and anti-inflammatory actions.
It is used to treat pain and inflammation in osteoarthritis,
rheumatoid arthritis and ankylosing spondylitis.
To treat acute pain from various sources, juvenile rheumatoid arthritis in children.
Used to treat primary dysmenorrhoea.
Pharmaceutical Formulations
Celecoxib capsule.
Brand Names
Celebrex, Celact, Celecap, Cetedol, Revibra, Colcibra.
Dose
100–200 mg twice daily.
Mefenamic Acid
It is an anthranillic acid derivative.
It is a COX-1 and COX-2 inhibitor.
It has analgesic, antipyretic and anti-inflammatory actions.
Properties
It is a white to greyish white crystalline powder.
It is odourless.
It has poor solubility in water.
It is soluble in acetone, chloroform, dichloromethane methanol.
Stability and Storage
It is stored in a well-closed container protected from moisture and light.
Uses
It has analgesic, antipyretic, anti-inflammatory action.
It is used to relieve mild to moderate pains.
Used in treatment of rheumatoid arthritis and osteoarthritis.
In inflammation and fever.
For the treatment of primary dysmenorrhoea.
Pharmaceutical Formulations
Mefenamic acid capsules.
Brand Names
Biospas, Ponstel, Lenagesic, Ponstan, Dotra-M.
Dose
250–500 mg thrice daily.
Aceclofenac
It is a phenyl acetic acid derivative.
It is a non selective COX inhibitor.
It inhibits both COX-1 and COX-2.
Properties:
It is a white crystalline powder.
It is freely soluble in acetone.
It is soluble in ethanol.
It is practically insoluble in water.
Stability and Storage
It is kept in an air-tight container in a cool and dry place, protected from light.
Uses
It is used to treat rheumatoid arthritis.
It is used to treat osteoarthritis.
It is used to treat ankylosing spondylitis.
Pharmaceutical Formulations
Aceclofenac tablet IP
Aceclofenac SR tablet.
Brand Names
Aceloc, Aceclo, Dolokind, Acerap, Aceact, Aceroc, Acent, Clanza.
Dose
100 mg twice daily.
Agents
1 Enlist various fungal infections. Define and classify
antifungal agents giving suitable examples.
☞ Fungal infections
Any disease caused by fungus is known as fungal infection.
Fungi are heterotropic microorganism.
A fungal infection is also called mycosis, a skin disease caused by a fungus.
Mycotic infections of human are:
Dermatophytoses is a contagious superficial skin infections. The diseases produced are ringworm of foot, ring-warm of skin, hair, nails.
Candidiasis can affect the skin and mucus membrane.
Saprophytes invade skin and penetrate deep causing lymphatic, pulmonary and systemic mycoses.
Fungal infections are:
Candidiasis: Caused by yeast candida.
Blastomycosis: Caused by the fungus blastomyces.
Ringworm: A common fungal infection.
Vaginal candidiasis.
Fungal nail infections.
Mucormycosis: Caused by mucormycetes.
Onchomycosis.
Histoplasmosis.
Antifungal Agents
The drugs which are used in the treatment of fungal infections are called antifungal agents.
Classification of Antifungal Agents:
Antibiotics, e.g. amphotericin-β, griseofulvin, nystatin.
Pyrimidine derivatives, e.g. 5-flucytosine.
241
Azoles/Imidazoles, e.g. clotrimazole, miconazole, ketoconazole.
Allylamines, e.g. terbinafine.
Thiocarbanilic acid derivatives, e.g.. tolnaftate.
Phenolic compounds, e.g.. salicylic acid.
Diamidines, e.g. stilbamidine.
Dyes, e.g. Gention violet, malachite green.
Unsaturated fatty acid: undecylenic acid.
2 Give the structure, chemical name, properties, stability and storage an uses of the following antifungal drugs.
Ketoconazole, (b) Fluconazole
☞ (a) Ketoconazole
It is a imidazole derivative.
Ketoconazole was first approved as an oral formulation for systemic use by the FDA in 1981.
Structure
Chemical Name
Acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2(1H-imidazole-1-ylmeth-yl)-1, 3-dioxolan-4-yl] methoxy] phenyl] piperazine.
Properties
It is a white to off-white crystalline powder.
It is freely soluble in dichloromethane.
It is soluble in chloroform and in methanol.
It is sparingly soluble in ethanol.
It is practically insoluble in water and in ether.
Stability and Storage
It is stored in a well closed container protected from light and at controlled room temperature.
Uses
It is a broad spectrum antifungal.
It is used to treat seborrheic dermatitis and fungal skin infections.
It is used orally to treat severe refractory cutaneous dermato-phytic infections.
Ketoconazole is used for the treatment of systemic fungal infections such as candidiasis, coccidioidomycosis, blastomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis.
Pharmaceutical Formulations:
Ketoconazole tablets IP
Ketoconazole lotion.
Ketoconazole cream.
Ketoconazole ointment.
Ketoconazole antidandruff shampoo.
Brand Names
Ketovate, Funginoc, Danruf, Nizrol, Funazole, Antanazol, Ketazole.
Dose
Adult dose, 200 to 400 mg once daily.
Fluconazole (Diflucan)
It is commonly known as “Diflucan”.
It is used for both systemic and superficial fungal infections.
Structure
Chemical Name
α-(2, 4-Difluorophenyl)-α-(1H-1, 2, 4-triazol-1-ylmethyl)-1H-1, 2, 4-triazole-1-ethanol.
OR
2,4-difluoro-α, α- bis(1H-1, 2, 4-triazol-1-ylmethyl) benzyl alcohol.
Properties
It is a white crystalline powder.
It is slightly soluble in water.
It is soluble in organic solvents such as chloroform, propylene glycol.
Stability and Storage
It should be stored in a tightly closed container at a temperature less than 30°C.
Uses
Fluconazole shows fungistatic activity.
It is used in the treatment of candidiasis.
Used to control oesophageal and oropharyngeal candidiasis.
An eye drop is useful in fungal keratitis.
Useful to treat vaginal candidiasis.
Pharmaceutical Formulations
Fluconazole tablets IP
Fluconazole capsules IP
Fluconazole oral suspension IP
Fluconazole eye drops.
Brand Names
Fluka, Fumycin, Diflucon, Wycon, Syscan, Zocon, Forcan, Fluzon.
Dose
100 to 200 mg per day.
3 Give the details of following antifungal agents:
(a) Amphotericin-B, (b) Griseofulvin, (c) Itraconazole,
(d) Naftifine hydrochloride, (e) Miconazole
☞ (a) Amphotericin-B
It is a polyene microlide antifungal agent.
Properties
It occurs as a yellow to orange powder.
It is almost odourless and tasteless.
It is practically insoluble in water and in alcohol.
Stability and Storage
It is affected by light, air and even at room temperature.
Hence, it is stored in tightly closed light-resistant containers at a temperature of 2° to 10°C.
Uses
It is effective in candidiasis, blastomycosis.
In cryptococcal meningitis.
For suppression of oral or intestinal candidiasis.
Pharmaceutical Formulations
Amphotericin-B cream.
Amphotericin-B lotion.
Amphotericin lozenges.
Amphotericin-B ointment.
Amphotericin-B injection.
Amphotericin mixture.
Brand Names
Fungizone, Fungilin, Ambilip, Ambisome, Amfitas.
Dose
50–100 mg four times daily.
Griseofulvin
Griseofulvin is obtained from the mold penicillium griseofulvin.
Properties
It occurs as a white or pale cream coloured powder.
It is tasteless and odourless.
It is very slightly soluble in water.
It is soluble in acetone and freely soluble in tetrachloroethane.
Stability and Storage
It is stored in tightly closed containers and kept away from oxidizing materials.
Uses
As an antifungal agent.
Used to treat dermatophytoses.
Used to treat ringworm infections.
Used to treat Tinea infections.
Pharmaceutical Formulations
Griseofulvin tablets.
Griseofulvin capsules.
Griseofulvin oral suspension.
Brand Names
G-fulvin, Grisovin, Bifulvin, Grifulvin-V, Gris-PECT, Grisoral, Walavin.
Dose
125–250 mg four times daily.
Itraconazole
Itraconazole is an orally active broad spectrum antifungal agent. It is a triazole derivative.
Properties
It is a white crystalline powder.
It is practically insoluble in water and in acidic solution.
Its melting point is 166.2°C.
Stability and Storage
It should be stored at room temperature and should be protected from light and moisture.
Uses
Used for the treatment of systemic fungal infections including blastomycosis, histoplasmosis (including patients infected with HIV)
Used to treat dermatophytosis.
Used to treat vaginal candidiasis.
Used to treat sporotrichosis.
Pharmaceutical Formulations
Itraconazole oral solution.
Itraconazole capsule.
Itraconazole injection.
Itraconazole concentrate, sterile BP
Brand Names
Candistat, Canditral, Flucover, Suntran, Ibitra.
Dose
200 mg once/twice daily with meals.
Naftifine Hydrochloride
Naftifine is a synthetic, broad spectrum antifungal agent.
It is allylamine derivative.
It is mainly used for topical treatment of tinea pedis, tinea cruris and tinea corpori.
Properties
It is a white crystalline powder.
It is soluble in polar solvents such as ethanol and methylene chloride.
Stability and Storage
It is stored in a well-closed container in cool and dark place, i.e. protected from light.
Uses
As topical antifungal agent.
For the treatment of tinea pedis, tinea cruris, tinea corpori.
Treatment of ringworm, athletes foot and jock itch.
Used in the treatment of ringworm of beard, ringworm of scalp and tinea versicolor.
Pharmaceutical Formulations
Naftifine cream.
Naftifine gel.
Brand Names
Naftin Gel, Tinaderm, Tinavate, Tolnaderm.
Miconazole
Miconazole is a broad spectrum azole/inidazole antifungal agent.
It is widely used to treat mucosal yeast infections.
Properties
It occurs as a white crystalline or micro crystalline powder.
It is sparingly soluble in methanol.
It is slightly soluble in ethanol and chloroform.
It is very slightly soluble in water and in ether.
Stability and Storage
It is stored at room temperature and protected from light and moisture. Miconazole vaginal suppositories should be stored at 15°C to 30°C.
Uses
As antifungal agent.
Used to treat fungal infections affecting the vagina, mouth and skin including candidiasis.
Used for the local treatment of oropharyngeal candidiasis in adult patients.
Used for the treatment of cryptococcosis, mucocutaneous candidiasis, coccidioidomycosis, cutaneous and vulvovaginal candidiasis.
Pharmaceutical Formulations
Miconazole tablets.
Miconazole gel.
Miconazole powder and solution.
Miconazole nitrate pessaries.
Miconazole cream (2%).
Miconazole nitrate vaginal tablets.
Miconazole ointments.
Miconazole spray.
Miconazole buccal tablet (50 mg)
Brand Names
Monistat Derm, Daktarin, Gynodaktarin, Zole, Orgvig.
Urinary Tract Anti-Infective
Agents
1 What are urinary tract anti-infective agents? Classify the urinary tract anti infective agents with examples.
☞ Urinary Tract Anti-infective Agents/Urinary Antiseptics
The drugs which are used to treat or prevent infections of urinary tract are called urinary tract anti-infective agents.
Classification
Quinolone derivatives
For example, norfloxacin, ciprofloxacin, moxifloxacin, ofloxacin lome floxacin.
Naphthyridine Derivatives
For example, nalidixic acid, enoxacin
Cinnoline derivatives
For example, cinoxacin.
Miscellaneous
For example, methenamine, nitrofurantioin, furazolidine.
2 Give the details of ‘ofloxacin’ as urinary tract anti-
infective agent.
☞ Ofloxacin
Ofloxacin is a synthetic fluonoquinolone antibiotic.
Structure
250
Chemical Name
Fluoro-2,3-dihydro-3-methyl-104(4-methyl-1-piperazin-yl)-7-oxo-7H-pyrido[1, 2, 3-de]-1,4,-benzoxazine-6-carboxylic acid.
Properties
It occurs as a pale yellow or bright yellow, crystalline powder.
It is soluble in glacial acetic acid.
It is slightly soluble in water, dichloromethane and methanol.
Stability and Storage
It should be stored at room temperature and should be kept away
from light and moisture.
Uses
It is useful in the treatment of genitourinary, respiratory, gastrointestinal infections.
It is used in the treatment of bronchitis and pneumonia.
It is used for the treatment of pelvic inflammatory disease.
It is useful for the treatment of acute gonococcal urethritis.
Used for the treatment of prostatitis caused by E.coli.
It is used for infections of skin and soft tissues.
Pharmaceutical Formulations
Ofloxacin tablets IP
Ofloxacin oral suspension IP
Ofloxacin ophthalmic solution IP
Ofloxacin infusion IP
Brand Names
Oflox, Exocin, Zenflox, Zanocin, Tarivid.
Dose
200 to 400 mg daily.
3 Give the properties, stability and storage, uses, formulations, brand names of the following drugs.
(a) Norfloxacin (b) Ciprofloxacin (c) Moxifloxacin.
☞ (a) Norfloxacin
Norfloxacin is a quinolone derivative.
Properties
It is a white to pale yellow, crystalline powder.
It has melting point of 221°C.
Its molecular weight is 319.34.
Stability and Storage
It is stored in a tightly closed light resistant container.
Uses
It is used as antibacterial agent.
It is used to treat urinary tract infections.
It is used to treat gynaecological infections.
It is used for the treatment of inflammation of prostate gland, gonorrhoea and bladder infection.
It is used to treat bacterial diarrhoea.
Pharmaceutical Formulations
Norfloxacin tablets IP
Norfloxacin suspension.
Norfloxacin eye drops IP
Brand Names
Norflox, Uroflox, Actiflox, Alflox, Bacigyl, Norilet, Norbactin.
Dose
400 to 800 gm daily in divided doses.
Ciprofloxacin
Ciprofloxacin is an antibiotic used to treat number of bacterial
infections.
Properties
It is a pale yellow, crystalline in nature.
It is slightly hygroscopic powder.
It is slightly soluble in methanol.
It is very slightly soluble in ethanol but insoluble in acetone,
ethyl acetate and methylene chloride.
It dissolves in acetic acid.
Stability and Storage
It should be stored in tight and light resistant containers at 2–25°C.
Uses
It is used for the treatment of urinary tract infection, prostatis and acute diarrhoeal disease caused by E.coli, shigella, salmonella.
It is used for the treatment of gonococcal urethritis, chancroid.
Used to treat infections of skin, soft tissues, bones and joints.
Used for the treatment of respiratory tract infections.
Also used for controlling bronchitis and pneumonia.
Pharmaceutical Formulations
Ciprofloxacin tablets IP.
Ciprofloxacin injection IP.
Ciprofloxacin eye drops IP.
Brand Names
Cilox, Cifran, Ciprobid, Ciprolet, Alcipro, Zoxan
Dose
250 to 750 mg twice daily.
Moxifloxacin
It is a synthetic fluoroquinolone antibiotic.
Properties
It is a slightly yellow crystalline powder.
It is soluble in water.
It is slightly hygroscopic.
Stability and Storage
It is stored in tightly closed containers protected from light and moisture.
Uses
Moxifloxacin is primarily used for pneumonia.
It is used in the treatment of conjunctivities endocarditis, tuberculosis and sinusitis.
Pharmaceutical Formulations
Moxifloxacin tablet.
Moxifloxacin eye drops (0.5%).
Brand Names
Moxicip, Moxeza, Moxoft, Avetox, Vigamox, Staxom, Milflox.
Dose
400 mg once daily.
Agents
1 Name the causative organism of tuberculosis. Define
and classify Anti-bercular agents with examples.
☞ Tuberculosis
Tuberculosis is a parasitic disease caused by Mycobacterium tuberculosis.
Antitubercular Agents
The drugs which are used for the treatment of tuberculosis are called antitubercular agents.
Classification of antitubercular agents
On chemical basis:
P-amino salicylic acid and analogues, e.g. p-amino salicylic (PAS) acid.
Pyridine derivative, e.g. isoniazid, ethionamide.
Pyrazine derivative, e.g. pyrazinamide.
Ethylene diamine derivative, e.g. ethambutol.
Antibiotics, e.g. cycloserine, streptomycin, rifampicin.
On the basis of clinical utility:
First line drugs (standard drugs/primary drugs): These are highly effective bactericidal agents, e.g. isoniazid, ri-fampin, pyrazinamide, ethambutol, streptomycin.
Second line drugs (reserve drugs/secondary drugs): These drugs have either low antitubercular efficacy, e.g. capreomycin, kanamycin, cycloserine, ethionamide, PAS, thioacetazone.
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2 Write a note on ‘isoniazid’ as antitubercular agent.
☞ Isoniazid (INH)
Structure
4
N 1
6 2
5 3
CONHNH2
Chemical Name
Iso-nicotinic acid hydrazide (INH) or pyridine 4-carboxazide
Properties
It occurs as a white crystalline powder.
It is odourless and has sweet taste.
It is soluble in water.
It is incompatible with aldehyde and ketone.
Stability and Storage
It is affected by light-hence it is stored in tightly closed light-resis-tant containers.
Uses
It is used in the treatment of pulmonary tuberculosis.
It is used in the treatment of meningitis and genitourinal infections.
Pharmaceutical Formulations
Isoniazid tablet.
Isoniazid elixir.
Isoniazid and ethambutol tablets.
Isoniazid and rifampicin tablets.
Sodium salicylate and isoniazid granules/powder.
Isoniazid injection.
Brand Names
Isonex, Isokin, Tubizid, Isovit, Cadizide, Isocadipas.
Dose
300 mg once daily.
2 Give the structure, chemical name, properties, stability and storage, uses, pharmaceutical formulations, brand names of pretomanid.
☞ Pretomanid
Pretomanid is an antimycobacterial agent that is administered with Bedaquiline and Linezolid to treat resistant forms of pulmonary tuberculosis.
It was the first antitubercular drug developed by a non-profit organization, known as TB Alliance and was granted FDA approval on 14th August 2019.
Structure
Chemical Name
(6S)-2-nitro-6-[[4-(trifluoro methoxy) phenyl]methoxy]-6, 7-dihy-dro-5H-imidazo[2, 1-b] [1, 3] oxazine.
Properties
It is white to yellow coloured crystalline powder.
It is practically insoluble in water.
Stability and Storage
It should be stored at room temperature below 30°C.
Uses
It is used to treat following disease conditions:
Non-responsive pulmonary multi-drug resistant tuberculosis.
Pulmonary extensively drug-resistant tuberculosis.
Treatment intolerant pulmonary tuberculosis.
Pharmaceutical Formulations
Pretomanid tablet.
Brand Name
Dovprela.
Dose
100–200 mg daily.
3 Give the properties, storage, uses, pharmaceutical formulations, brand names of the following antitubercular drugs.
Ethambutol, (b) Para-amino salicylic, (PAS) acid
(c) Pyrazinamide, (d) Rifampicin, (e) Bedaquiline,
(f) Delamanid.
☞ (a) Ethambutol (Ethylenediamine derivative) Structure
Properties
It occurs as a white crystalline powder.
It is odourless, bitter in taste and hygroscopic in nature.
It is soluble in water and alcohol and insoluble in chloroform
and ether.
A solution of ethambutol in water is dextrorotatory.
Stability and Storage
It should be stored in a well tightly closed container and protected from light.
Uses
It is a tuberculostatic agent.
It is used in the treatment of pulmonary tuberculosis.
Pharmaceutical Formulations
Ethambutol HCl tablet BP, IP.
Ethambutol powder.
Brand Names
E-tibi, Mycobutol, Combutol, Zytham, Albutol, Myambutol.
Dose
15 mg/kg per day.
Para-amino Salicylic (PAS) Acid
Structure
4
3
2
1
NH2
5
6
OH
COOH
Chemical Name
4-amino, 2-hydroxy benzoic acid
Properties
It occurs as a white or yellowish white crystal.
It is odourless and has slightly acidic taste.
It is slightly soluble in water.
Its sodium salt is very soluble in water.
Stability and Storage
It darkens on exposure to air and light. Hence, it is stored in tightly closed light-resistant containers.
Uses
It is a bacteriostatic.
It is used in the treatment of tuberculosis.
Brand Names
Benzapar, Idipas, Parasal, Monopas, Paser, Isopar, Benzapas.
Pharmaceutical Formulations
Calcium aminosalicylate tablet IP.
Sodium aminosalicylate tablet IP.
Sodium aminosalicylate granules IP.
Amino salicylic acid tablets.
Amino salicylate potassium tablets.
Benzoyl PAS calcium tablets.
Dose
10–12 gm per day in divided doses.
Pyrazinamide
Structure
3
2
N 4
5
6
N CONH2
1
Chemical Name
Pyrazine-2-carboxamide or 2-carbamoyl pyrazine
Properties
It occurs as a white crystalline powder.
It is odourless and has slightly bitter taste.
It is sparingly soluble in water but soluble in ether and chloroform.
Stability and Storage
It is stored in a tightly closed light-resistant container.
Uses
It is used as a tuberculostatic.
Pharmaceutical Formulations
Pyrazinamide tablet IP, BP.
Brand Names
Zinamide, Pyrina, PZA ciba, Pyride, Pyrina-500.
Rifampicin
Properties
It occurs as a brick red crystalline powder.
It is odourless.
It is very slightly soluble in water.
It is soluble in chloroform.
It is unstable in the presence of moisture.
Stability and Storage
Rifampicin is unstable in the presence of moisture. It is affected by light, air and oxygen. Hence it is stored in tightly closed light resistant containers in an atmosphere of nitrogen and a temperature not exceeding 15°C.
Uses
It is used to treat:
Tuberculosis.
Bacillary dysentery.
Meningitis.
Pharmaceutical Formulations
Rifampicin capsules
Rifampicin oral suspension BP.
Brand Names
Rimpin, Rimpacin, R-cin, Monocin
Bedaquiline
Bedaquiline is a diarylquinoline antimycobacterial used in combination with other antibacterials to treat pulmonary multidrug resistant tuberculosis (MDR-TB).
Properties
It is a white powder.
It is insoluble in water.
Stability and Storage
It is stored in tightly closed containers protected from light and moisture.
Uses
It is used as a part of combination therapy in adults with pulmonary multidrug resistant tuberculosis (MDR-TB).
Pharmaceutical Formulation
Bedaquiline tablet.
Brand Names
Sirturo.
Dose
400 to 600 mg per day.
Delamanid
Delamanid is an antitubercular agent derived from the nitro-dihydro-imidazo-oxazole class of compound.
Properties
It is a white to pale yellow crystals or crystalline powder.
It is practically insoluble in water.
It is slightly soluble in methanol.
Stability and Storage
It is stored at room temperature below 25°C.
Uses
Delamanid is used along with other antitubercular medications for active multidrug resistant tuberculosis.
It is given in combination with linezolid, levofloxacin, and
pyrazinamide.
Pharmaceutical Formulation
Delamanid tablet.
Brand Name
Deltyba
Dose
100 mg per day
Agents
1 Define and classify antiviral drugs with examples.
☞ Antiviral Agents:
The drugs which are used in the treatment of viral infections are called antiviral agents.
Classification of antiviral drugs:
Drugs acting as anti-herpes virus
For example, Idoxuridine, acyclovir, favipiravir, foscarnet.
Drugs acting as anti-influenza virus
For example, Amantidine
Drugs acting as anti-hepatitis virus
For example, Ribavirin
Drugs acting as anti-retrovirus
For example, Zidovudine (AZT)
2 Give the details of “Acyclovir” as antiviral agent.
☞ Acyclovir
Acyclovir is a synthetic analogue of the purine nucleoside, guaosine with potent antiviral activity against herpes simplex viruses type 1 and 2, varicella-zoster virus and other viruses of the herpes virus family.
Structure
264
Chemical Name
amino-9-(2-hydroxyethoxymethyl) purine-6-olate, or 2-ami-no-9-[(hydroxyethoxy) methyl]-1, 9, dihydro-6H-purin-6-one.
Properties
It is a white or almost white crystalline powder.
It is slightly soluble in water.
It is soluble in dimethyl sulphoxide and dilute mineral acids.
It is very slightly soluble in ethanol.
Stability and Storage
It should be stored at room temperature and protected from light and moisture.
Uses
It is used as antiviral agent against herpes viruses.
It has been approved for short-term treatment of chickenpox.
Oral acyclovir is used in the initial treatment of genital herpes and to control mild recurrent episodes.
It shows antiviral activity against varicella-zoster virus.
Pharmaceutical Formulations
Acyclovir tablet IP
Acyclovir oral suspension IP
Acyclovir intravenous infusion IP
Acyclovir sodium intravenous infusion.
Acyclovir cream IP
Acyclovir eye ointment IP
Brand Names
Acivir, Ocuvir, Herpex-200, Cyclovir, Zovirax, Aciv, Aciherpin.
Dose
200 to 800 mg, 4 to 5 times daily.
3 Give properties, stability and storage, uses, pharmaceutical formulations. Brand names of the following antiviral drugs.
(a) Amantidine, (b) Idoxuridine, (c) Foscarnet, (d) Zidovudine, (e) Ribavirin, (f) Remdesivir, (g) Favipiravir
☞ (a) Amantidine
It is a synthetic tricyclic amine which prevents replication of influenza virus.
Properties
It is a white crystalline powder.
It sublimes when heated.
It is soluble in water and in alcohol.
Chemically it is adamantan-1-amine.
Stability and Storage
It undergoes decomposition at 360°C. It is stable in light, heat and air. It should be stored in a tightly closed containers at room temperature (15°C to 30°C)
Uses
It is used as an antiviral drug.
It is used in the treatment of various strains of influenza A
virus.
Amantidine is used in the treatment of Parkinson’s disease.
It is also used as a dapamine receptor agonist.
Amantidine is used for the treatment of many prototypes of
influenza A virus (H1N1, H2N2, Asian type, H3N2)
Amantidine is used for the treatment of cerebral arteriosclerosis.
It is used to relieve fatigue.
Pharmaceutical Formulations
Amantidine tablet.
Amantidine capsule.
Amantidine syrup.
Amantidine solution.
Brand Names
Amantrel, Camantral, Neaman, Osmolex.
Dose
100 to 200 g daily in two divided doses.
Idoxuridine
It was the first pyrimidine antimetabolite to be used of antiviral
drug.
It is a nucleoside analogue of deoxyuridine and containing a
halogenated pyrimidine.
Properties
It is white or almost white crystalline powder.
It is odourless.
It is slightly soluble in water and ethanol.
It is practically insoluble in ether.
It dissolves in dilute solutions of alkali hydroxides.
Stability and Storage
It should be stored in a tightly and light resistant container and stored between 2°C and 8°C.
Uses
It is an antiviral agent against herpes virus.
It is used for topical treatment of herpes keratitis.
It is used for the treatment of herpes labialis, gentalis and zoster.
It is used for the topical treatment of herpes simplex virus (HSV) keratitis.
It is used in ophthalmic for the treatment of HSV kerato-conjunctivitis.
Pharmaceutical Formulations
Iodoxuridine ophthalmic solution.
Iodoxuridine ophthalmic ointment.
Iodoxuridine eye drops IP.
Brand Names
Idrin, Xurin, Herplex, Dendrid, Toxil.
Foscarnet
Foscarnet is a selective inhibitor of viral DNA polymerase that
inhibits replication in herpes viruses.
Foscarnet can act synergistically with nucleoside triphosphate
antimetabolite in the inhibition of viral DNA synthesis.
The chemical name of foscarnet sodium is phosphonoformic
acid, trisodium salt.
Properties
It is a white crystalline powder.
It is soluble in water.
It is practically soluble in ethanol.
Its molecular weight is 300.1.
Stability and Storage
It is stored in tightly closed containers protected from light and moisture. It should be stored between 20°C and 25°C.
Uses
Foscarnet is used to treat cytomegalovirus (CMV) in retinitis in people with AIDS.
Foscarnet is also used to treat herpes simplex virus (HSV) in people with a weak immune system.
Foscarnet is used to control opportunistic infections in patients with AIDS.
Pharmaceutical Formulations
Foscarnet sodium intravenous infusion BP.
Brand Name
Foscavir.
Zidovudine (Azidothymidine)
It is a deoxythymidine analogue and is reverse transcriptase inhibitor.
Properties
It is an odourless, off-white powdered solid.
It is soluble in ethanol and in methanol.
It is sparingly soluble in water.
Stability and Storage
It is a heat and light sensitive, hence it should be protected from light and stored at room temperature.
Uses
It is an effective antiviral drug.
Zidovudine is effective against HIV-1, HIV-2, HTLV-1 and many other retroviruses.
Zidovudine is useful in treatment of symptomatic HIV infections.
Zidovudine is also used in anaemia in AIDS patients.
Zidovudine is a drug choice for post-exposure prophylaxis of HIV, as well as for mother off-spring transmission.
Pharmaceutical Formulations
Zidovudine tablets IP.
Zidovudine capsules IP.
Zidovudine syrup.
Zidovudine oral solution IP.
Zidovudine injection IP.
Zidovudine, lamivudine and nevirapine tablets IP.
Brand Names
Retrovir, Zidovir, Viro-Z, Zydowin, Zidomax.
Dose
300 mg twice daily.
Ribavirin
Ribavirin is a broad spectrum direct antiviral agents.
Ribavirin is efficient both in vitro and in vivo against several RNA or DNA viruses.
Ribavirin inhibits the replication of a very wide variety of RNA
and DNA viruses.
Properties
It is a white crystalline powder.
It is soluble in water.
It is slightly soluble in ethanol and in methylene blue.
It is very slightly soluble in dichloromethane.
Stability and Storage
It should be stored in a tightly closed container protected from light.
Uses
Ribavirin is used in the treatment of influenza type-A and
type-B, hepatitis, genital herpes and Lassa fever.
It is used for treatment of severe lower respiratory infections caused by RSV.
Oral ribavirin is used in chronic hepatitis C.
Nebulized ribavirin is used for respiratory syncytial virus, bronchitis in infants and children, particularly those with congenital heart disease.
Pharmaceutical Formulations
Ribavirin syrup.
Ribavirin capsule.
Ribavirin inhalation solution IP.
Ribavirin powder to be reconstituted in an aqueous aerosol.
Brand Names
Ribavin virazole, virazide, Rebetol, Ibavyr.
Remdesivir
Remdesivir is a prodrug of an adenosine triphosphate (ATP)
analogue.
Remdesivir has potential antiviral activity against a variety of
RNA viruses.
Remdesivir is first described in the literature in 2016 as a potential treatment of Ebola.
Remdesivir being a prodrug, is metabolized into its active form
GS-441524.
Properties
It is a white or off-white crystalline powder.
It is soluble in DMSO, ethanol.
It is insoluble in water.
Stability and Storage
It is stored in tightly-closed containers protected from light and moisture.
Uses
Remdesivir is used for the treatment of coronavirus disease 2019 (COVID-19) infection requiring hospitalization.
It is useful for the treatment of SARS-COV-2 virus in hospitalized adult and children 12 years of age.
Remdesivir is an antiviral drug.
Remdesivir helps to stop the spread of the virus throughout the body.
Remdesivir is used as a potential treatment of Ebola.
Remdesivir activity against the coronaviridae family was first
demonstrated in 2017, for the treatment of COVID-19.
Pharmaceutical Formulations
Remdesivir injection.
Remdesivir lyophilized powder for reconstitution.
Brand Names
Covifor, Veklury, Redyx, Cipremi, Remdac.
Dose
By I.V., 200 mg as a single dose on day 1, followed by 100 mg once daily. Duration is generally 5 days.
Favipiravir
Favipiravir is a pyrazine carboxamide derivative with activity
against RNA viruses.
It is an antiviral drug used to manage influenza that has the
potential to target other viral infections.
Favipiravir is known to be teratogenic, therefore, should be
avoided in pregnancy conditions.
Favipiravir is extensively metabolized with metabolities exerted
mainly in the urine.
Properties
It occurs as a white crystalline powder.
It is slightly soluble in water.
It has melting point 187°C to 193°C.
Stability and Storage
It is stored in a tightly closed container protected from light and air.
Uses
Favipiravir is an antiviral drug used to manage influenza.
Used in the treatment of avian influenza.
Recently favipiravir is used in COVID-19 infection and has the potential to target other viral infections.
Pharmaceutical Formulations
Favipiravir tablet.
Brand Names
Avifavir, Areplivir, Avigan, Favimed, BAL Flu
Dose
1800 mg orally twice daily for COVID-19.
Antimalarials
1 What is malaria? Give the causative agents of malaria.
☞ Malaria:
Malaria is a mosquito-born disease caused by the malarial parasite (Plasmodium) which belongs to class protozoa.
Malaria is transmitted through a bite of female anopheles vector and the host is human being.
Malaria is caused by four Plasmodium species, namely:
Plasmodium vivax.
Plasmodium falciparum.
Plasmodium malariae.
Plasmodium ovale.
The symptoms of malarial infections are:
Chills followed by fever, anaemia.
Enlargement of liver.
Body pains and sweating.
Plasmodium falciparum causes severe and fatal form of malaria. It destroys a large number of blood cells causing anaemia. It also penetrates the tissue of organs like brain, spleen, kidney, etc. penetration in brain tissue may be fatal.
The main important protozoal diseases of man are: Amoebiasis, malaria, trypanosomiasis, chagas, disease, trichomoniasis, leishmaniasis, giardiasis.
2 Define and classify antimalarial drugs with suitable
examples.
☞ Antimalarials:
The drugs which are used for prevention and treatment of malaria are called antimalarials.
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Classification of antimalarials:
(I) On the basis of site of action:
Sporonticide (Sporozoitocides): These are effective sporo-zoites, e.g. pyrimethamine.
Tissue schizonticides: These are effective at pre-erythrocytic stage, e.g. primaquine, proguanil, pyrimethamine.
Blood schizonticides: These are effective at erythrocytic stage.
Fast-acting schizonticides, e.g. quinine, chloroquine, amodiaquins e.
Slow-acting schizonticides, e.g. proguanil, pyrimeth-
amine.
Gametocides: These drugs are effective gametes, e.g. primaquine, quinine.
(II) On Chemical Basis:
Cinchona alkaloids, e.g. quinine.
4-aminoquinoline derivatives, e.g. chloroquine, amodiaquine, mefloquine.
8-aminoquinoline derivaties, e.g. primaquine.
9-amino acridine derivatives, e.g. mepacrine.
Biguanide derivative, e.g. proguanil.
2,4-diaminopyrimidine derivatives, e.g. pyrimethamine, trimethoprim.
Miscellaneous:
Sulphonamides, e.g. protonsil.
Sulphones, e.g. dapsone.
3 Give the structure, chemical name, properties, stability and storage uses, pharmaceutical formulations, Brand names of the following antimalarials. (a) Chloroquine,
(b) Mefloquine.
☞ (a) Chloroquine (4-aminoquinoline derivative)
Structure
N
7
6
5
4
8 1
Cl
2
3
1 2 3 4
C2H5
Chemical Name
NH CH CH3
CH2 CH2 CH2 N
C2H5
7-chloro 4 (4-diethyl amino-1-methyl butylamino) quinoline
Properties
It is a white crystalline powder.
It is odourless and has a bitter taste.
It is freely soluble in water but slightly soluble in chloroform.
Storage
It is discoloured in the presence of sunlight and hence it is stored in well-closed, light-resistant container.
Uses
It is used in the treatment of malaria.
It is also used to treat hepatic amoebiasis.
It is used to treat giardiasis.
It is used to treat rheumatoid arthritis.
Pharmaceutical Formulations
Chloroquine phosphate tablet.
Chloroquine phosphate injection.
Chloroquine sulphate tablet.
Chloroquine sulphate injection.
Hydroxychloroquine sulphate tablet.
Brand Names
Ciplaquin, Nivaquin, M-quin, Resochin.
Mefloquine
It is the newer 4-amino quinoline derivative.
Chemical Name
(R S) - [2,8-bis 13 (trifluoro methyl) quinolone-4-yl] [(2SR) piperdin 2-yl] methanol hydrochloride.
Properties
It is a white or slightly yellow crystalline powder.
It is soluble in ethanol, and in ethylacetate.
It is slightly soluble in water.
Stability and storage
It is stored in tightly-closed container protected from light.
Uses:
Mefloquine is an antimalarial effective against P. falciparum.
Mefloquine may inhibit merozoite invasion.
Mefloquine is used for prophylaxis of malaria among travellers to areas with multidrug resistance.
Mefloquine is effective against chloroquine-resistant forms of
Plasmodium falciparum. Pharmaceutical Formulations Mefloquine Tablets IP.
Brand Names
Mefque, Facital, Lariam, Confal
Dose
5 mg/kg per week.
4 Give the details of the following antimalarial drugs.
quinine sulphate, (b) primaquine phosphate,
(c) cycloguanil, (d) pyrimethamine, (e) artemisinin
☞ (a) Quinine Sulphate
Quinine is the chief alkaloid of cinchona bark (fever bark).
Quinine was the first drug having significant antimalarial activity.
Properties
It occurs as a white, microcrystalline powder.
It is odourless and intensely bitter in taste.
It is slightly soluble in ether and chloroform.
Quinine sulphate is slightly soluble in water.
Storage and Stability
It should be stored in a tightly closed container, protected from light.
Uses
It is a highly active blood schizonticide and is also gametocide.
It is used as antimalarial agent.
It is used to treat severe and complicated malaria caused by
P. falciparum.
It is used to treat cerebral malaria.
It is used to relieve muscle cramps in myotonia congentia.
It is used as a sclerosing agent with urethane.
Pharmaceutical formulations
Quinine sulphate tablets IP.
Quinine hydrochloride tablets.
Quinine dihydrochloride injection IP.
Brand Names
Vigotab, flue-foe, Qualaquin, Quinarsol-300, Cinkona.
Primaquine Phosphate
It is 8-amino-quinoline derivative.
Properties
It is an orange-red-crystalline powder.
It is odourless and has a bitter taste.
It is soluble in water.
It is practically insoluble in alcohol.
Stability and Storage:
It is affected by light and moisture, hence it is stored in well-closed light-resistant containers protected from moisture.
Uses
It is mainly used for a radical cure of P. vivax infection in conjunction with chloroquine.
It is an antimalarial having tissue schizonticide and gametocide activity.
Pharmaceutical Formulations
Primaquine tablets.
Brand Names
Aralon, Primalex, Leoprime, Malirid.
Cycloguanil
Cycloguanil is the active metabolite of proguanil.
Cycloguanil is a dihydrofolate reductase inhibitor.
Cycloguanil (proguanil) intereferes with deoxythymidylate synthesis by inhibiting dihydrofolate reductase.
Stability and Storage
It is stored in tightly-closed container protected from light.
Uses
It is used for malarial prophylaxis alone or in combination with chloroquine.
Its combination with atovaquone as a fast-acting erythrocyte schizonticide for the treatment of multidrug-resistant falciparum malaria.
It is used as a clinical curative for vivax malaria.
Pharmaceutical Formulation
Proguanil tablet.
Brand Names
Progumal, Paluride, Micromedex, Malarone.
Pyrimethamine
It is a 2,4-diaminopyrimidine derivative.
Structure
1
C2H5
N
6
5
4
NH2
2
NH2
N3
Cl
Chemical Name
2,4-diamino, 5 (p-chlorophenyl) 6-ethyl pyrimidine
Properties
It is a white crystalline powder.
It is odourless and tasteless.
It is practically insoluble in water.
It is soluble in warm dilute mineral acids.
Storage
It should be stored in a tightly closed, light-resistant containers.
Uses
It is used in the treatment of malaria.
It is used to treat toxoplasmosis.
Preparations
Pyrimethamine tablet IP, BP.
Pyrimethamine and sulphadoxine injection.
Pyrimethamine and sulphadoxine tablet.
Brand Names
Daraprim, Pyralfin, Onli-2.
Dose
25–50 mg per day.
Artemisinin:
Artemisinin is derived from the leaves and flowers of the annual mugwort (Artemisia annua).
Artemisinin is used in traditional Chinese medicine for centuries.
Artemisinin, its semisynthetic derivatives are collectively known as Artesunate and Artemether.
Artemisinin is a sesquiterpene lactone obtained from sweet worm wood, Artemisia annua.
Properties
It is soluble in organic solvents such as ethanol, DMSO and DMR.
Artemisinin is sparingly soluble in aqueous buffers.
Stability and Storage
It is stored in well-closed container.
Uses
Used as antimalarial agent.
In treatment of schizophrenia.
Useful to treat parasitic worms (Helminths)
Artemisinin has a clinical impact potential in treatment of COVID-19.
Pharmaceutical Formulations
Artemisinin tablets.
Artemisinin capsule.
Artemisinin extract powder.
Brand Names
Antoxipan, Vinilex Ivermectin.
Sulphonamides
1 What are sulphonamide? Explain the structures of sulphanilamide and para-aminobenzoic acid (PABA).
☞ Sulphonamides:
Sulphonamides are the antibacterial agents containing sul-phonamido group (–SO2 NH2) and are the derivatives of sulphanilamide.
They are also called sulpha drugs.
The first sulphonamide was trade named protonsil, which is first commercially available antibacterial drug.
Structure of protonsil:
Structure of sulphanilamide and PABA:
Paul Ehrlich is known as Father of Chemotherapy.
Mechanism of Action of Sulphonamides
Sulphonamide has structural similarity to para-amino benzoic acid (PABA).
Hence it competes with PABA in bacterial metabolism.
Folic acid derived from PABA is important in bacterial metabolism.
280
Sulphonamide inhibits the bacterial enzyme folic acid synthe-tase which is useful for conversion of PABA into folic acid.
This causes folic acid deficiency resulting in injury to the bacterial cell.
Such injured cells can be phagocytosed easily.
2 Define and classify sulphonamides giving suitable
examples.
☞ Sulphonamides:
“Sulphonamides are the antimicrobial compounds containing a sulphonamide group (–SO2NH2) and are the derivatives of sulpha-nilamide.”
Classification of Sulphonamides
Sulphonamides are classified on chemical basis:
N1 substituted sulphonamides, e.g. sulphacetamide, sulphadiazine, sulphaguanidine, sulphamethoxazole.
N4 substituted sulphonamides, e.g. sulphasalazine.
Both N1 and N4 substituted sulphonamides, e.g. phthalylsulphathiazole, succinylsulphathiazole.
As per therapeutic use sulphonamides are classified as:
Used in eye infection, e.g. sulphacetamide.
Used in intestinal infection, e.g. sulphaguanidine, succinylsulphathiazole, phthalylsulphathiazole.
Used in urinary tract infection, e.g. sulphamethoxazole, trimethoprim, sulphadiazine.
Used in respiratory tract infection, e.g. co-trimoxazole, sulphadiazine.
Used in burn therapy, e.g. silver sulphadiazine, mefenide.
On the basis of duration of action:
Short acting (4 to 8 hrs) sulphonamides:
e.g. sulphadiazine, sulphathiazole, sulfisoxazole, sulphamethi-azine, sulphasomidine, sulphamethizole.
Intermediate acting (8 to 16 hrs) sulphonamides:
e.g. sulphaphenazole, sulphamethoxazole.
Long acting (1 to 7 days) sulphonamides:
e.g. sulphadimethoxine, sulphamethoxypyridazine.
3 Write the structures, chemical names, properties, uses, formulations and brand names of the following sulphonamides: (a) Sulphacetamide (b) Dapsone.
☞ (a) Sulphacetamide (Sulphonamide used in eye infection)
Structure
5 6
4
1
H2N SO2NH COCH3
3 2
Chemical Name
N-acetyl sulphanilamide OR
P-aminobenzene sulphonyl acetamide.
Properties
It occurs as a white crystalline powder.
It is soluble in water and alcohol.
Aqueous solutions are acidic to litmus.
It has a saline taste.
Storage
It should be stored in well-closed light-resistant containers.
Uses
As antibacterial.
It is used to treat eye infections.
It is used to treat urinary tract infections.
Pharmaceutical formulations
Sulphacetamide eye drops.
Sulphacetamide eye ointment.
Sulphacetamide tablet.
Brand Names
Albucid, Nebasulf, Eycula.
Dapsone Diaminodiphenylsulphone (DDS)
Dapsone is a sulphone. The term sulphone is used for all the derivatives containing 4,4-diaminodiphenylsulphone. In this class the amino group of sulphamoyl group of sulphanilamide is replaced by p-aminophenyl group.
4,4’ diaminodiphenylsulphone OR Bis (4-aminophenyl) sulphone
Properties
It occurs as a white or creamy white crystalline powder.
It is odourless and has slightly bitter taste.
It is very slightly soluble in water and soluble in acetone and in dilute mineral acids.
Stability and Storage
It is stored in a well-closed light-resistant container.
Uses
In the treatment of leprosy.
It has suppressive action on malarial parasite.
It is also used in the treatment of dermatitis.
Combination of dapsone with pyrimethamine is used to treat pneumonia.
Pharmaceutical Formulations
Dapsone tablet IP.
Dapsone tablet BP.
Dapsone tablet USP.
Brand Names
Dubronax, Novaphone, Aczone.
Dose
100 mg per day
4 What is co-trimoxazole? Give the properties, uses, mechanism of actions, formulations, brand names of co-trimoxazole, OR Write a note on co-trimoxazole.
☞ Co-trimoxazole
Co-trimoxazole is a mixture of 5 parts of sulphamethoxazole and 1 part of trimethoprim.
The two components of co-trimoxazole interfere with the bacterial synthesis of tetrahydrofolic acid which is an essential stage in the production of nucleic acids.
Sulphamethoxazole inhibits the synthesis of dihydrofolic acid from PABA and trimethoprim inhibits the action of dihydrofolate reductase and prevents the synthesis of tetrahydrofolic acid from dihydrofolic acid.
Sulphamethoxazole (SMX)
It is a sulphanilamide derivative.
It is a white crystalline powder.
It is odourless and has bitter taste.
It is very slightly soluble in water.
Trimethoprim (TMP)
It is a pyrimidine derivative.
It is a white to yellowish powder.
It is odourless and has bitter taste.
It is very slightly soluble in water.
When sulphamethoxazole is given alone, a resistance develops to susceptible bacteria and needs higher doses.
Trimethoprim also develops resistance when given alone. When combination of these two drugs is used, the spectrum of antibacterial activity is increased.
This is due to synergistic effect.
Uses of Co-trimoxazole
It is used in:
Urinary tract infections.
Respiratory tract infections like bronchitis, pneumonia.
Meningitis.
Enteric infections like typhoid and paratyphoid.
Ear infections such as otitis media.
Mechanism of Action of Co-trimoxazole:
PABA is essential for bacterial growth.
Sulphamethoxazole and trimethoprim act synergistically by blocking the formation of folic acid and its utilisation. This combination is called co-trimoxazole (5 : 1).
Sulphamethoxazole inhibits the conversion of PABA into dihydrofolic acid by inhibiting the enzyme dihydrofolic acid synthe-tase.
Trimethoprim inhibits conversion of dihydrofolic acid into tetrahydrofolic acid by inhibiting the enzyme dihydrofolic acid reductase.
Tetrahydrofolic acid (THF) is necessary in purine and DNA synthesis.
So, co-trimoxazole inhibits both steps in bacterial metabolism and acts as antibacterial.
Stability and Storage
It is stored in tightly-closed containers protected from light and moisture.
Pharmaceutical Formulations
Co-trimoxazole tablet
Co-trimoxazole injection
Dispersible co-trimoxazole tablet
Paediatric co-trimoxazole tablet
Paediatric co-trimoxazole mixture.
Brand Names
Ciplin-DS, Septran, Bactrim-DS (double strength), Bactrin-DS, Uritrim.
5 Write a note on sulphanilamide.
☞ Sulphanilamide
Sulphanilamide was synthesized for the first time in 1908 by Austrian Chemist Paul Josef Jakob Gelmo.
Structure
Sulphonamide group is attached to aniline known as sulphanilamide.
Properties
Sulphanilamide is a white powder.
It is soluble in water, glycerol.
It is insoluble in chloroform, ether, benzene, etc.
Stability and Storage:
It is stored in a tightly-closed containers protected from light.
Uses
It is used as anti-infective/antibacterial.
It is used to treat vulvovaginal candidiasis caused by Candida albicans, Trichomonas vaginalis, and Gardnerella vaginalis.
Pharmaceutical Formulations
Sulphanilamide cream.
Sulphanilamide suppositories.
6 Describe the following sulphonamides in detail.
Sulphadiazine (b) Mafenide acetate.
☞ (a) Sulphadiazine
N 6
N
3
4
2
5 6 1
4
1
H2N SO2 NH 5
3 2
Chemical Names
2 (P-amino benzene sulphonamido) pyrimidine OR
N1-(Pyrimidin-2-yl) sulphanilamide
Properties
It is a white crystalline powder.
It is practically insoluble in water.
It is soluble in solutions of alkali hydroxides and carbonates.
It is slightly alkaline in taste.
Stability and Storage
It should be stored in a well tightly closed container and protected from light.
Uses
Sulphadiazine is used in the treatment of:
Meningitis
Burns
Urinary tract infection
Toxoplasmosis. Pharmaceutical Formulations Sulphadiazine tablet IP, BP.
Sulphadiazine sodium injection BP.
Brand Names
Pyrimol, Adiazine, Cotrizine, Trimozin, Atrina.
Mafenide acetate
Mafenide is a synthetic sulphonamide analogue of PABA with topical anti-infective activity.
It is only used topically to inhibit a variety of gram-positive and gram-negative bacteria.
Properties
It is a white crystalline powder.
It is slightly soluble in water.
It is soluble in DMSO.
Stability and Storage
It is stored in a well-closed container.
Uses
Mafenide acetate is used in the treatment of slow-healing, infected wounds.
To treat burns.
It is used as topical antimicrobial agent to control bacterial infection when used under moist dressings.
Pharmaceutical Formulations
Mafenide acetate cream.
Mafenide acetate powder or solution.
Brand Name
Sulfamylon.
Antibiotics
1 Define and classify antibiotics giving examples.
☞ Antibiotics
Antibiotics are chemical substances produced by living organisms, which are capable of inhibiting the growth of other microorganisms, in small concentration.
☞ Classification of Antibiotics
On the basis of Spectrum of Antimicrobial Activity:
Narrow Spectrum Antibiotics
The antibiotics which are selectively effective on gram +ve or gram –ve bacteria or fungi or yeast are called narrow spectrum antibiotics. For example, bacitracin, nystatin, benzyl penicillin.
Broad Spectrum Antibiotics
The antibiotics which are effective on a large number of pathogens, not only gram +ve and gram –ve bacteria but also affect the intracellular organisms like viruses and rickettsiae are called broad spectrum antibiotics. For example, tetracyclines, chloramphenicol, streptomycin, penicillins.
On the basis of Chemical Structure/Lactam Ring:
b-lactam Antibiotics
For example, benzyl penicillin, benzathin penicillin, ampicillin, phenoxymethyl penicillin, cloxacillin, cephalexin, carben-cillin, cephaloridine.
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Nonlactam Antibiotics
Antibiotics containing hydronaphthacene ring, e.g. tetracyclines.
Aminoglycoside antibiotics, e.g. streptomycin, neomycin, gentamycin, kanamycin.
Macrolide antibiotics, e.g. erythromycin.
Anthracycline antibiotics, e.g. actinomycin, daunorubicin.
Polyene macrolide antibiotics, e.g. nystatin, amphotericin B.
Peptide antibiotics, e.g. bacitracin.
Nonclassifiable antibiotics, e.g. griseofulvin, chloramphenicol.
Miscellaneous antibiotics, e.g. novabiocin, rifamycin.
2 What are penicillins? Explain the basic structure of penicillin and 6-amino penicillanic acid (6-APA). What are b-lactam antibiotics?
☞ Penicillins
Penicillin is the first antibiotic discovered by Alexander Fleming. They are obtained from mould Penicillium chrysogenum and Penicillium notatum.
Penicillins contain b-lactam ring, a 4-membered cycle amide, fused with thiazolidine ring.
This gives bicyclic heterocyclic system called penam.
6-Amino Penicillanic Acid (6-APA)
Basic Structure of Penicillins
☞ b-Lactam Antibiotics
b-Lactam antibiotics are the antibiotics which contain a be-ta-lactam ring in their molecular structure, e.g. Penicillins, cephalosporins, cephamycins, carbapenems, carbacephems.
b-lactam antibiotics are used in the management and treatment of bacterial infections.
b-lactam is a cyclic amide with four atoms in its ring system.
It is named as such because the nitrogen atom is attached to the beta-carbon atom relative to the carbonyl group in the four-membered ring.
3 Who is the founder of penicillin? Classify penicillins giving examples.
☞ Penicillin:
Penicillin was discovered in 1929 by Alexander Fleming in
England.
It is extracted from the mould Penicillium notatum and Penicillium chrysogenum.
☞ Classification of Penicillins:
Natural penicillins, e.g. benzyl penicillin, phenoxymethyl-
penicillin.
Acid-resistant penicillins, e.g. ampicillin, cloxacillin, phenoxy-
methylpenicillin.
Penicillinase-resistant penicillins, e.g. oxacillin, cloxacillin, methicillin.
Broad spectrum penicillins, e.g. ampicillin, carbenicillin.
Penicilling effective against pseudomondas e.g. Carbenicillin.
4 Give the structure chemical names, properties, uses and formulations of the following drugs: (a) Penicillin-G
(b) Amoxicillin.
☞ (a) Benzyl Penicillin (Penicillin-G)
Structure:
Chemical Name:
6-(2-phenoxyacetamido) penicillanic acid
Property
It is a white, finely crystalline powder.
It has faint characteristic odour.
It is hygroscopic.
It is very soluble in water.
It is dextrorotatory.
Stability and Storage
If the moisture content of benzyl penicillin is less than 0.5%, then at room temperature it is stable for 2–3 years.
Hence, it is stored in tightly closed containers protected from moisture.
Uses
It is used to treat:
Abscesses.
Syphilis.
Gonorrhoea.
Pharyngitis, pneumonia, meningitis, endocarditis due to staphy-lococci.
Pneumonia, endocarditis due to streptococci.
Pneumococcal infection.
Tetanus, diphtheria, anthrax.
Otitis media.
Pharmaceutical Formulations
Benzyl penicillin injection.
Benzyl penicillin eye drops.
Benzyl penicillin eye ointment.
Procaine penicillin injection.
Fortified procaine penicillin injection.
Brand Names
Novapen, Crystapen-G, Pentids, Benpen, Bicillin CR, Pfizerpen
Amoxicillin
It is a b-lactam antibiotic of penicillin group.
It is a semisynthetic derivative of penicillin.
Structure:
Chemical Name:
Sodium (6R) 6-(a-4-hydroxy phenyl D-glycylamino) penicillanate.
Properties
It is a white crystalline powder.
It is very soluble in water.
It is sparingly soluble in anhydrous ethanol.
It is very slightly soluble in acetone.
Stability and Storage
It is stored at room temperature betwen 20 and 25°C and is kept away
from excess heat and moisture.
Uses
It is used to treat bacterial infections like bronchitis, middle ear infection, throat infection, pneumonia, skin infections and urinary tract infections.
It is effective against gram-negative bacteria.
Pharmaceutical Formulations
Amoxicillin capsule IP.
Amoxicillin injection IP.
Amoxicillin oral suspension IP.
Amoxicillin dispersible tablets IP.
Amoxicillin and potassium clavulanate tablets IP.
Amoxicillin and potassium clavulanate injection IP.
Amoxicillin tablet.
Brand Names
Amoxil, Amoxylin, Novamox, Mox, Polymox, Purimox, Larotid,
Synamax, Trimox.
5 Write notes on: (a) Cloxacillin and (b) Streptomycin.
☞ (a) Cloxacillin
It is a semisynthetic penicillin.
Properties
It is white crystalline powder.
It is soluble in water, methanol, ethanol.
It is slightly hygroscopic.
Stability and Storage
It is stored at room temperature between 15 and 30°C and is kept
away from light and moisture.
Uses
Cloxacillin is used to treat the following infections:
Respiratory tract infection.
Urinary tract infection.
Otitis media.
Endocarditis.
Bone and joint infections.
Septicaemia.
Meningitis.
Pharmaceutical Formulations:
Cloxacillin capsules I.P.
Cloxacillin syrup I.P.
Cloxacillin injection I.P.
Brand Names
Ampiclox, Cloxin, Cloxa-A, Bioclox, Klox, Amclo.
Streptomycin (Aminoglycoside antibiotic)
Streptomycin was the first aminoglycoside antibiotics introduced in chemotherapy in 1944 by Waskman.
Streptomycin was obtained/derived from Streptomyces griseus.
Streptomycin is called aminoglycoside because its structure
consists of amino sugar linked by glycosidic linkage.
Streptomycin contains two strongly polar and basic guanidino groups and one weakly basic methyl amino group. Hence, it acts as triacidic base.
Streptomycin is the first antibiotic active against tuberculi bacilli for the treatment of Tuberculosis in 1952.
Streptomycin acts by binding the bacterial 30S ribosomal subunit.
Properties
It is white to off-white powder.
It is odourless.
It has slightly bitter taste.
It is very soluble in water but sparingly soluble in alcohol.
It is strongly basic in nature.
Stability and Storage
It is affected by moisture, light and heat and hence it is stored in well-closed containers protected from moisture and at a temperature not exceeding 30°C.
Uses
It is a broad spectrum aminoglycoside antibiotic and is anti-
bacterial.
It is used to bacterial infections such as:
Tuberculosis
Pneumonia
Influenza
Plague
Mycobacterium avium complex
Endocarditis
Brucellosis
Tubercular meningitis
Cholecystitis and peritonitis.
Pharmaceutical Formulations:
Streptomycin tablets IP.
Streptomycin injection IP.
Brand Names
Streptomac, Ambistryn-S, Chlorostrep, Enterostrop, Lykastrep,
Cipstryn.
6 What are tetracyclines? Give its source. Give the basic structure of tetracyclines. Classify tetracyclines giving examples.
☞ Tetracyclines
Tetracyclines are broad spectrum antibiotics and are effective
against gram +ve and gram –ve bacteria.
Tetracyclines are octahydronaphthacene derivatives.
The tetracyclines contain octahydrotetracene-2-carboxamide
skeleton as structural unit.
Tetracyclines are derived directly from bacterium known as
Streptomyces coelicolor.
In 1945, chlortetracycline (prototype) of tetracycline was discovered by Dr. Benjamin.
7-chlortetracycline (aureomycin) was the first member among tetracyclines. It was introduced in 1947, obtained from Streptomyces aureofaciens.
Oxytetracycline (Tetramycin) was produced by Streptomyces rimosus.
☞ Classification of Tetracyclines:
Naturally occurring, e.g. chlortetracycline, oxytetracycline,
demeclocycline.
, e.g. doxycycline, minocycline, rolitetracycline.
☞ Tetracycline
Structure:
Chemical Name:
4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-Pentahydroxy-6-methyl-1,11-dioxonaphthacene-2-carboxamide.
Properties
It is a yellow crystalline powder.
It is odourless and has bitter taste.
It is very slightly soluble in water and dilute acids.
It is levorotatory.
Stability and Storage
It darkens in strong sunlight and in presence of moisture. Hence,
it is stored in tightly-closed, light-resistant containers.
If it is used for parenteral preparation, the container should be
sterile and sealed, so as to exclude the microorganism.
Uses
It is a broad spectrum antibiotic and is used to treat:
Plague.
Cholera.
Syphilis, gonorrhoea.
Chronic bronchitis.
Amoebic dysentery.
Chlamydial infection of eye.
Urinary tract infection.
Balantidiasis.
Gram +ve, gram –ve and rickettsial infections.
Pharmaceutical formulations:
Tetracycline tablet.
Tetracycline capsule.
Tetracycline injection.
Tetracycline eye ointment.
Tetracycline and procaine injection.
Tetracycline intravenous injection.
Brand Names
Resticlin, Terramycin, Enterocycline, Achromycin.
7 Give the details of the following tetracyclines:
(a) Doxycycline, (b) Minocycline.
☞ (a) Doxycycline
Doxycycline is a tetracycline antibiotics that is effective against bacterial infection.
Properties
It is yellow, crystalline powder.
It has a slightly ethanolic odour.
It is hygroscopic.
It is soluble in water.
It is practically insoluble in chloroform and in ether.
It is soluble in solution of alkali hydroxides and carbonates.
Stability and Storage
It is stored at room temperature in a tightly closed light-resistant container.
Uses
It is used to treat infections such as:
Acne.
Urinary tract infections.
Intestinal infections.
Respiratory infections.
Eye infections.
Periodontitis (gum disease).
Gonococcal urethritis.
In malaria.
Pharmaceutical Formulations
Doxycycline hydrochloride capsules IP.
Doxycycline dispersible tablets IP.
Doxycycline syrup.
Brand Names
Novadox, Tetradox, Monodox, Adoxa, Doxypal, Doxicip, Doxt, Peristat.
(b) Minocycline
Minocycline is a second generation tetracycline antibiotic effective against gram +ve and gram –ve bacteria.
Properties
with slight bitter taste.
sparingly soluble in water.
slightly soluble in ethanol.
solutions of alkali hydroxides and carbonates.
Stability and Storage
It is slightly hygroscopic and sensitive to light. Hence, it is stored in
a tightly-closed airtight container and kept in a dry place.
Uses
It is used to treat a number of bacterial infections such as acne
vulgaris, pneumonia and rheumatoid arthritis.
It is used to treat infections caused by rickettsiae, Mycoplasma pneumoniae, Chlamydia trachomatis.
Pharmaceutical Formulations
Minocycline tablets BP.
Minocycline capsules BP.
Minocycline prolonged-release capsules BP.
Brand Names
Arestin, Minocin, Dynacin, Amzeeq, Solodyn, Ximino.
Dose
100 mg per day.
8 What are macrolide antibiotics? Classify them with examples.
☞ Macrolide Antibiotics
Macrolides are the class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars are attached.
Macrolide belongs to polyketide class of natural products.
Macrolides are derived from Saccharopolyspora erythraea.
Macrolide produces the action by binding to the 50s ribosomal
subunit, thereby inhibiting the protein synthesis.
☞ Classification of Macrolide Antibiotics
1st generation macrolides, e.g. picromycin, erythromycin.
2nd generation macrolides:
14-Membered ring, e.g. clarithromycin, roxithromycin, flurithromycin, dirithromycin.
15-Membered ring, e.g. azithromycin.
3rd generation macrolides, e.g. spiramycin, tylosin, carbomy-cin.
9 Write notes on:
Erythromycin, (b) Azithromycin.
☞ (a) Erythromycin
It belongs to a group of drugs called macrolide antibiotics.
It is obtained from Streptomyces erythreus.
Properties
It is a white or slightly yellow crystalline powder.
It is slightly soluble in water.
It is soluble in organic solvents such as ethanol, DMSO.
It is odourless and has a bitter taste.
It is hygroscopic in nature.
Stability and Storage
It should be stored in a tightly closed light-resistant container at 15–30°C.
Uses
It is a drug of choice to treat pneumonia, urethritis, pelvic inflammation.
It is used to treat amoebic dysentery.
It is used to treat wounds and burn infection.
It is also used in the treatment of intestinal amoebiasis.
Used to treat gonorrhoea and syphilis.
Pharmaceutical Formulations
Erythromycin tablet.
Erythromycin injection.
Erythromycin soluble powder.
Erythromycin estolate capsule BP.
Erythromycin stearate tablet BP, IP.
Brand Names
Erythrocin, Althrocin, Erycin, Erysert, Acnederm, Acnelak.
Azithromycin
It is a broad spectrum antibiotics belongs to macrolide class.
It is a semisynthetic derivative of erythromycin.
Properties
It is white or almost white powder.
It is freely soluble in anhydrous ethanol and in dichloromethane.
It is practically insoluble in water.
Stability and Storage
It is stored in a well-closed container protected from excess heat and
moisture.
Uses
It is used for the treatment of pharyngitis and tonsillitis.
It is more effective against gram-negative bacteria.
It is used to treat respiratory tract infection.
It is used to treat urinogential and sexually transmitted infections.
Used to treat pneumonia.
Pharmaceutical Formulations
Azithromycin tablet IP.
Azithromycin capsule IP.
Azithromycin oral suspension.
Azithromycin dry syrup.
Azithromycin injection.
Brand Names
Azithral, Zithromax, Aziwok, Aziwin, Azro, Glenazee.
Dose
500 mg per day.
10 Give the structure, chemical name, stability and storage, uses and preparations of chloramphenicol.
☞ Chloramphenicol
It is a broad spectrum antibiotic. It is a propane 1,3-diol derivative.
Structure
4
1
NO2
5 3
6 2
HO C H O
1
Chemical Name
H 2 C NH C CHCl2
3 CH2OH
2-dichloroacetamido, 1 (p-nitrophenyl) propane 1, 3-diol
Properties
It occurs as a white or greyish white crystalline powder.
It is odourless and has very bitter taste.
It is slightly soluble in water.
Stability and Storage
It is stable in solid form but is affected by light and hence it is stored in well-closed light-resistant containers. If the material is used for parenteral preparation the container should be sterile and sealed so as to exclude microorganism.
Uses
Chloramphenicol is a broad spectrum antibiotic and is used to treat:
Typhoid and paratyphoid fever.
Meningitis.
Urinary tract infection.
Rickettsial infection.
Infection of eye and ear.
Superficial infection of the skin.
Septicaemia (brain abscess).
Pharmaceutical Formulations
Chloramphenicol capsules.
Chloramphenicol ear drops.
Chloramphenicol eye ointment.
Chloramphenicol injection.
Chloramphenicol palmitate suspension.
Brand Names
Chloromycetin, Chlorostrep, Enteromycin, Fenicol, O-mycin.
11 Give the properties, storage, uses, formulations, brand names of clindamycin.
☞ Clindamycin
Clindamycin is a semisynthetic chloro derivative of lincomycin.
Lincomycin is a natural antibiotics produced by the actinobacte-rium Streptomyces lincolnensis.
Properties
It is a white crystalline powder.
It is very soluble in water.
It is slightly soluble in ethanol.
It is odourless.
Stability and Storage
It is hygroscopic, hence it is stored in a tightly closed container protected from moisture.
Uses
Clindamycin is used most commonly to treat gram-positive
cocci infections.
It is used for the treatment of bacterial infections such as:
Acne.
Joint infections.
Pelvic inflammatory disease.
Strep throat.
Pneumonia.
Upper respiratory tract infection.
Middle ear infections.
Endocarditis.
Pharmaceutical Formulations
Clindamycin capsules IP.
Clindamycin injection IP.
Clindamycin cream,
Clindamycin suppository.
Clindamycin palmitate oral suspension IP.
Brand Names
Clindac, Clinzee, Clincia, Dalcinex, Acnesol, Clindests.
Antineoplastic/Anticancer
Agents
1 What is cancer (neoplasm/tumour)? Mention the types of cancer.
☞ Cancer
Cancer means a relatively autonomous growth of tissues.
Cancer is a disease in which some of the body’s cell grow uncontrollably and spreads to other parts of the body through blood and lymph systems.
Cancer is a group of diseases characterized by abnormal and uncontrolled growth of the cells with ability of invade and destory adjacent tissues and even distant organs.
Types of cancer:
Carcinomas: These are developed from ectodenmal or endodermal cells, e.g. skin cancer, brain cancer.
Sarcomas: These cancers develop in connective tissues and mesoderm, e.g. bone cancer.
Lymphomas: These are developed from lymph glands. In this type glands are enlarged lymphocytes are more in numbers.
Leukemias: It is developed from blood tissue. It is called blood cancer. WBCs are increased and RBCs are decreased.
Benign tumour is growing slowly while malignant tumour is growing fastly.
Some common features of cancer are excessive cell proliferation, tumour may develop, invades surrounding cells, may produce new cancerous growth.
Cancer chemotherapy began in 1940 when stilbestrol phosphate was introduced for treating cancer of prostate gland.
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2 Define and classify anticancer/antineoplastic drugs
with suitable examples.
☞ Anticancer drugs
The drugs which are used in the treatment of cancer/neoplasm are called anticancer/antineoplastic/antitumour agents.
Classification of antineoplastic/anticancer drugs
Alkylating agents, e.g. chlorombucil, melphalan, busulfan, cyclophosphamide, thiotepa, carmstine, lomustine, dicarba-zine, semustinee.
Antimetabolite:
Purine antagonist, e.g. 6-mercaptopurine, azathioprine.
Pyrimidine antagonist, e.g. 5-fluorouracil (5-FU) cytara-bine.
Folate antagonist, e.g. methotrexate, trimetrexate.
Vinca alkaloids, e.g. vinblastine, vincristine.
Antibiotics, e.g. actinomycin D, mitomycin, daunorubicin, bleomycins.
Radioisotopes, e.g. radioiodine, radiogold.
Hormones, e.g. androgens, estrogens, progestins, corticosteroids.
Enzymes, e.g. L-asparrginase.
Taxanes, e.g. paclitaxel, docetaxel.
Epipodophyllotoxin, e.g. etoposide.
Camptothecin analogues, e.g. irinotecan, topotecan.
Miscellaneous, e.g. cisplatin, hydroxyurea, procarbazine, car-boplatin, imatinib.
3 What are alkylating agents? Explain in detail cyclophosphamide.
☞ Alkylating agents
Alkylating agents are highly reactive drugs that bind to certain chemical groups (phosphate, amino, sulphydril, hydroxyl, and imidazole groups) commonly found in nucleic acids and other macromolecules, bringing about charges in the DNA and RNA of cells.
Alkylating agent used in cancer treatment that attaches an alkyl group to DNA.
Alkylating agents interfere with DNA replication by cross-link-ing DNA strands, DNA strand breaking and abnormal pairing of base pairs.
The following are alkylating agents used in the treatment of cancer:
Chlorambucil is an aromatic nitrogen mustard effective against chronic lymphocytic leukemia, malignant lymphomas, and carcinoma of breast and ovary.
Busulphan is mainly used to treat gastrointestinal and breast cancer.
Cyclophosphamide is effective against malignant lymphomas, lymphoblastic leukaemia, and various carcinomas.
Cisplatin is used to treat testicular cancer, ovarian cancer, bladder cancer, etc.
Cyclophosphamide
Cyclophosphamide is an alkylating agent used as anticancer drug.
Structure
Chemical Name
(RS) 2-Bis(2-chloroethyl)aminoperhydro-1, 3, 2-oxazaphosphorine-2-oxide monohydrate
Properties
It occurs as a fine, white crystalline powder.
It is odourless and has slight bitter taste.
It is soluble in water.
It is very soluble in alcohol but very slightly soluble in ether.
Its melting point is between 41° and 45°C.
Stability and Storage
It is sensitive to light, heat and moisture, hence stored in tightly closed containers and away from light.
Uses
It is an anticancer drug used to treat:
Breast cancer.
Lung cancer.
Cancer of ovary.
Malignant lymphomas.
Multiple myeloma.
Chronic leukaemias.
Hodgkin’s disease.
Neuroblastoma.
Ewing’s sarcoma.
It is used as an immunosuppressive agent.
Pharmaceutical formulations:
Cyclophosphamide tablet IP.
IP.
Brand Names
Cycloxan, Endoxan-Asta, Ledoxan.
4 Write a note on the following antineoplastic agents.
(a) Fluorouracil, (b) Cisplatin
☞ (a) Fluorouracil
It is an antimetabolite antineoplastic agent.
It is a nucleobase analogue.
Structure
Chemical Name
5-fluorouracil.
Properties
It is a white crystalline powder.
It is odourless.
It is soluble in water.
It is very slightly soluble in alcohol.
Stability and Storage
It is affected by air and light, hence it is stored in tightly closed, light-resistant containers.
Uses
It is a cytotoxic (antineoplastic agent).
It is the most active drug against colorectal cancer.
It is used to treat solar keratoses and other malignant conditions of skin.
It is used in the treatment of cancers of breast, colon, stomach, head, neck, bladder, etc.
Used in the palliative treatment of neoplasm of gastrointestinal tract, breast and pancrease and respiratory tract.
Pharmaceutical formulations Fluorouracil injection IP. Brand Names
Fluracil, Fivocil, Oncpurcil, Flocil, Florac, Fivoflu.
(b) Cisplatin
with alkylating properties.
DNA and RNA chains.
y.
Structure
Cl NH3
Pt
Cl NH3
Properties
white crystalline solid.
water and soluble in dimethyl formamide.
Stability and Storage
It should be stored in a well tightly closed container and protected from light and stored at a temperature between 2° and 8°C.
Uses
y.
solid tumours including those of the bladder, prostate and head and neck.
Brand Names
Neoplastin, Plastinex, Platinol, Aquaplat.
Pharmaceutical formulations
Cisplatin injection IP.
5 Explain following anticancer/antineoplastic drugs.
(a) Busulphan, (b) Mercaptopurine, (c) Methotrexate,
(d) Dactinomycin, (e) Doxorubicin hydrochloride,
(f) Vinblastine sulphate, (g) Dromostanolone propionate
☞ (a) Busulphan
It is an alkylating agent.
Properties
white crystalline powder.
slightly soluble in water and soluble in acetone.
Storage
It is stored in tightly closed light-resistant container.
Pharmaceutical Formulations
Busulphan tablet BP, IP. Brand Names Myleran, Misulban.
Uses
a vera.
Mercaptopurine (6-Mercaptopurine) (6MP)
It is a purine antagonist type of antimetabolite used as antineoplastic drug.
Properties
It is a yellow crystalline powder.
It is odourless.
It is very slightly soluble in water.
It is soluble in solutions of alkali hydroxides.
Stability and Storage
It is affected by air and light and hence it is stored in tightly closed, light-resistant containers protected from moisture.
Uses
It is used in the treatment of acute monocytic leukaemia, lymphoblastomas, myeloblastoma leucosis and to treat neuroleukemia.
It is used to treat:
Acute lymphatic leukaemia.
Acute myelogenous leukaemia.
Chronic granulocytic leukaemia.
It is also an immunosuppressive agent used to treat nephrotic syndrome, autoimmune disease like haemolytic anemia, severe rheumatoid arthritis.
In conjunction with folic acid antagonists, it is used to treat choriocarcinoma.
Pharmaceutical Formulations Mercaptopurine tablet IP. Brand Names
Mercapthol, Purinethol, Empurine, Purixan, Empurine.
Dose
250 mg/kg per day.
Methotrexate
It is a folate antagonist from antimetabolite class used as antineoplastic.
Properties
It is yellow to orange brown crystalline powder.
It is odourless.
It is insoluble in water, alcohol, chloroform, ether.
It is slightly soluble in dilute hydrochloric acid.
Stability and Storage
It is affected by air and light and hence it is stored in a tightly closed light-resistant container.
Uses:
It is an antineoplastic drug used to treat:
Acute lymphoblastic leukaemia.
Acute lymphocytic leukaemia.
Lung cancer.
Neck cancer.
Epidermoid cancer of the head and breast.
Ovarian and testicular cancer.
Medulloblastoma.
Severe psoriasis.
Pharmaceutical Formulations
Methotrexate tablets IP.
Methotrexate injection IP.
Brand Names
Neotrexate, Biotrexate.
Dactinomycin (Actinomycin-D)
It is a chromopeptide antineoplastic antibiotic isolated from the bacterium streptomyces parvulus.
Properties
It is a bright red crystalline powder.
It occurs as lyophylised powder.
It is soluble in alcohol and alcohol–water mixture.
It is very slightly soluble in water.
Stability and Storage
It is affected by light, excessive heat and moisture, hence it is stored in light-resistant containers.
Uses
It is an antineoplastic agent used to treat:
Pelvic or limb tumours.
Rhabdomyosarcoma.
Testicular and ovarian malignant teratomas.
Wilms’ tumour in children.
Pharmaceutical Formulations
Dactinomycin injection.
Brand Names:
Cosmagen, Lyovac
Dose
15 mg/kg IV per day.
Doxorubicin Hydrochloride
Doxorubicin is an anthracycline antibiotic with antineoplastic activity.
Doxorubicin is isolated from the bacterium Streptomyces peu-cetius.
It intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis.
Properties
It is a red, crystalline solid.
It is odourless.
It is hygroscopic.
It is soluble in water, soluble in aqueous alcohol.
It is insoluble in non-polar organic solvents.
Stability and Storage
It is kept in tightly closed container under an inert atmosphere and stored under ambient temperature.
Uses
It is an antineoplastic/anticancer agent.
It is used in the treatment of acute lymphocytic leukaemia.
With other drugs, it is used to treat solid tumours.
It is used for the treatment of:
Leukemias.
Wilms’ tumour.
Neuroblastoma.
Small cell lung cancer.
Ovarian and testicular cancer.
Acute myeloid as well as lymphoblastic leukemia.
Breast, thyroid, bladder cancer.
Pharmaceutical Formulations
Doxorubicin HCl tablet IP.
Doxorubicin HCl injection IP.
Doxorubicin HCl injection BP.
Brand Names
Adriamycin, Dounocin, Daunomycin, Oncodria, ADM, Adria.
Dose
66–75 mg/m2 BSA by slow IV injection every 3 weeks.
Vinblastine sulphate
Vinblastine is a natural alkaloid isolated from the plant
Catharanthus roseus with antineoplastic properties.
Vinblastine disrupts microtubule formation and function during mitosis and intereferes with glutamic acid metabolism.
Vinblastine is a part of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) regimen used in the treatment of Hod-gkin’s lymphoma.
Properties
It is a white or yellowish amorphous or crystalline powder.
It is freely soluble in water.
It is soluble in methanol.
It is practically insoluble in ethanol and in ether.
Stability and Storage
It is kept in tightly closed container under inert atmosphere and stored under ambient temperatures.
Uses
It is an antineoplastic drug used in the treatment of:
Severe lymphoblastic leukemia.
Hodgkin’s disease.
Neuroblastoma.
Sarcoma.
Lymphocytic lymphoma.
Histiocytic lymphoma.
Advanced testicular carcinoma.
In choriocarcinoma and breast cancer.
Pharmaceutical Formulations
Vinblastine injection
Brand Names
Biocristin, Velban, Velsar, VLB, Uniblastin, Cytoblastin.
Dromostanolone propionate
It is a synthetic androgen or male hormone similar to testosterone.
It is an anabolic steroid related to dihydrotestosterone that has antiestrogenic effect.
Properties
It is a white to creamy white crystalline powder.
It has melting point of 128°C.
Stability and Storage
It is kept in tightly closed container under an inert atmosphere and stored under ambient temperatures.
Uses
It is an antineoplastic/anticancer agent used to treat:
Breast cancer in women.
Ovarian cancer.
Gestational trophoblastic neoplasm.
Metastatic testicular tumours.
Local recurrent solid tumours. Pharmaceutical Formulations Dromostanolone propionate injection. Brand Names
Masteril, Masteron, Drolban, Mastisol, Permastril, Prometholone.