Syllabus for GPAT Pharmaceutical Chemistry
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- Importance of inorganic compounds in pharmacy and medicine; An outline of methods of preparation, uses, sources of impurities, tests for purity and identity, including limit tests for iron, arsenic, lead, heavy metals, chloride, sulphate and special tests if any, of the following classes of inorganic pharmaceuticals included in Indian Pharmacopoeia: Gastrointestinal Agents: Acidifying agents, Antacids, Protectives and Adsorbents, Cathartics; Major Intra-and Extra-cellular Electrolytes: Physiological ions. Electrolytes used for replacement therapy, acid-base balance and combination therapy; Essential and Trace Elements: Transition elements and their compounds of pharmaceutical importance, Iron and haematinics, mineral supplements; Cationic and anionic components of inorganic drugs useful for systemic effects; Topical Agents: Protectives, Astringents and Anti-infectives; Gases and Vapors: Oxygen, Anesthetics (inorganic) and Respiratory stimulants; Dental Products: Dentifrices, Anti-caries agents; Complexing and chelating agents used in therapy; Miscellaneous Agents: Sclerosing agents, Expectorants, Emetics, Inorganic poisons and antidotes. Pharmaceutical Aids Used in Pharmaceutical Industry: Anti-oxidants, Preservatives, Filter aids, Adsorbents, Diluents, Excipients, Suspending agents, Colorants; Acids, Bases and Buffers: Buffer equations and buffer capacity in general, buffers in pharmaceutical systems, preparation, stability, buffered isotonic solutions, measurements of tonicity, calculations and methods of adjusting isotonicity. Water; Inorganic Radiopharmaceuticals: Nuclear reaction, radioisotopes, radiopharmaceuticals, Nomenclature, Methods of obtaining their standards and units of activity, half-life, measurement of activity, clinical applications, dosage, hazards and precautions.
- Importance of basic fundamentals of physical chemistry in pharmacy; Behaviour of Gases: Kinetic theory of gases, deviation from ideal behavior and explanation; The Liquid State: Physical properties (surface tension, parachor, viscosity, refractive index, dipole moment); Solutions: Ideal and real solutions, solutions of gases in liquids, colligative properties, partition coefficient, conductance and its measurement, Debye Huckel theory; Thermodynamics: First, Second and Third laws, Zeroth law, Concept of free energy, enthalpy and entropy, absolute temperature scale; Thermochemical equations; Phase rule; Adsorption: Freudlich and Gibbs adsorption, isotherms, Langmuir's theory of adsorption; Photochemistry: Consequences of light absorption, Jabolenski diagram, Quantum efficiency; Chemical Kinetics: Zero, First and Second order reactions, complex reactions, theories of reaction kinetics, characteristics of homogeneous and heterogeneous catalysis, acid base and enzyme catalysis; Quantum Mechanics: Postulates of quantum mechanics, operators in quantum mechanics, the Schrodinger wave equation. Importance of fundamentals of organic chemistry in pharmaceutical sciences; Structure and Properties: Atomic structure, Atomic orbitals, Molecular orbital theory, wave equation, Molecular orbitals, Bonding and Anti-bonding orbitals, Covalent bond, Hybrid orbitals, Intramolecular forces, Bond dissociation energy, Polarity of bonds, Polarity of molecules, Structure and physical properties, Intermolecular forces, Acids and bases; Stereochemistry: Nomenclature, isomerism, stereoisomerism, conformational and configurational isomerism, optical activity, specification of configuration, Reactions involving stereoisomers, chirality, conformations; Stereoselective and stereospecific reactions; Structure, Nomenclature, Preparation and Reactions of: Alkanes, Alkenes, Alkynes, Cyclic analogs, Dienes, Benzene, Polynuclear aromatic compounds, Arenes, Alkyl halides, Alcohols, Ethers, Epoxides, Amines, Phenols, Aldehydes and ketones, Carboxylic acids, Functional derivatives of carboxylic acids, a, β-Unsaturated carbonyl compounds, Reactive intermediates-carbocations, carbanions, carbenes and nitrenes; Nucleophilic and Electrophilic Aromatic Substitution Reactions: Reactivity and orientation; Electrophilic and Nucleophilic Addition Reactions; Rearrangements (Beckman, Hoffman, Benzilic acid, pinacole-pinacolone and Beyer-Villiger); Elimination reactions; Conservation of Orbital Symmetry and Rules: Electrocyclic, Cycloaddition and Sigmatropic reactions; Neighboring group effects; Catalysis by transition metal complexes; Heterocyclic Compounds: Nomenclature, preparation, properties and reactions of 3, 4, 5, 6 & 7-membered heterocycles with one or two heteroatoms like 0, N, S. Chemistry of lipids, Carbohydrates and Proteins.
- Biochemistry in pharmaceutical sciences; The concept of free energy: Determination of change in free energy-from equilibrium constant and reduction potential, bioenergetics, production of ATP and its biological significance; Enzymes: Nomenclature, enzyme kinetics and their mechanism of action, mechanism of inhibition, enzymes and iso-enzymes in clinical diagnosis; Co-enzymes: Vitamins as co-enzymes and their significance. Metals as cofactors and their significance; Carbohydrate Metabolism: Conversion of polysaccharides to glucose-1-phosphate, Glycolysis, fermentation and their regulation, Gluconeogenesis and glycogenolysis, Metabolism of galactose and galactosemia, Role of sugar nucleotides in biosynthesis, and Pentose phosphate pathway; The Citric Acid Cycle: Significance, reactions and energetics of the cycle, Amphibolic role of the cycle, and Glyoxalic acid cycle; Lipids Metabolism: Oxidation of fatty acids, β-oxidation & energetics, biosynthesis of ketone bodies and their utilization, biosynthesis of saturated and unsaturated fatty acids, Control of lipid metabolism, Essential fatty acids & eicosanoids (prostaglandins, thromboxanes and leukotrienes), phospholipids, and sphingolipids, Biosynthesis of eicosanoids, cholesterol, androgens, progesterone, estrogens corticosteroids and bile acids; Biological Oxidation: Redox-potential, enzymes and co-enzymes involved in oxidation reduction & its control, The respiratory chain, its role in energy capture and its control, energetics of oxidative phosphorylation. Inhibitors of respiratory chain and oxidative phosphorylation, Mechanism of oxidative phosphorylation; Metabolism of ammonia and nitrogen containing monomers: Nitrogen balance, Biosynthesis of amino acids, Catabolism of amino acids, Conversion of amino acids to specialized products, Assimilation of ammonia, Urea. Cycle, metabolic disorders of urea cycle, Metabolism of sulphur containing amino acids; Purine biosynthesis: Purine nucleotide inter-conversions; Pyrimidine biosynthesis: And formation of deoxyribounucleotides; Biosynthesis of Nucleic Acids: Brief introduction of genetic organization of the mammalian genome, alteration and rearrangements of genetic material, Biosynthesis of DNA and its replications; Mutation: Physical & chemical mutagenesis/carcinogenesis, DNA repair mechanism. Biosynthesis of RNA; Genetic Code and Protein Synthesis: Genetic code, Components of protein synthesis and Inhibition of protein synthesis.
- Basic Principles of Medicinal Chemistry: Physico-chemical and stereoisomeric (Optical, geometrical) aspects of drug molecules and biological action, Bioisosterism, Drug-receptor interactions including transduction mechanisms; Drug metabolism and Concept of Prodrugs; Principles of Drug Design (Theoretical Aspects): Traditional analog and mechanism based approaches, QSAR approaches, Applications of quantum mechanics, Computer Aided Drug Designing (CADD) and molecular modeling; Synthetic Procedures, Mode of Action, Uses, Structure Activity Relationships including Physicochemical Properties of the Following Classes of Drugs: Drugs acting at synaptic and neuro-effector junction sites: Cholinergics, anti-cholinergics and cholinesterase inhibitors, Adrenergic drugs, Antispasmodic and anti-ulcer drugs, Local Anesthetics, Neuromuscular blocking agents; Autacoids: Antihistamines, Eicosanoids, Analgesic-antipyretics, Anti-inflammatory (non-steroidal) agents. Steroidal Drugs: Steroidal nomenclature (IUPAC) and stereochemistry, Androgens and anabolic agents, Estrogens and Progestational agents, Oral contraceptives, Adrenocorticoids; Drugs acting on the central nervous system: General Anesthetics, Hypnotics and Sedatives, Anticonvulsants, Anti-Parkinsonian drugs, Psychopharmacological agents (Neuroleptics, Anti-depressants, Anxiolytics), Opioid analgesics, Anti-tussives, CNS stimulants; Diuretics; Cardiovascular drugs: Anti-hypertensives, Anti-arrythmic agents, anti-anginal agents, Cardiotonics, Anti-hyperlipedemic agents, Anticoagulants and Anti-platelet drugs; Thyroid and Anti thyroid drugs; Insulin and oral hypoglycemic agents; Chemotherapeutic Agents used in bacterial, fungal, viral, protozoal, parasitic and other infections, Antibiotics: β-Lactam, macrolides, tetracyclines, aminoglycosides, polypeptide antibiotics, fluoroquinolones, Anti-metabolites (including sulfonamides); Anti-neoplastic agents; Anti-viral agents (including anti-HIV); Immunosuppressives and immunostimulants; Diagnostic agents; Pharmaceutical Aids; Microbial Transformations: Introduction, types of reactions mediated by micro-organisms, design of biotransformation processes, selection of organisms, biotransformation process and its improvements with special reference to steroids; Enzyme Immobilization: Techniques of immobilization, factors affecting enzyme kinetics, Study of enzymes such as hyaluronidase, penicillinase, streptokinase, amylases and proteases, Immobilization of bacteria and plant cells.
- Different techniques of pharmaceutical analysis, Preliminaries and definitions: Significant figures, Rules for retaining significant digits, Types of errors, Mean deviation, Standard deviation, Statistical treatment of small data sets, Selection of sample, Precision and accuracy, Fundamentals of volumetric analysis: Methods of expressing concentration, primary and secondary standards: Acid Base Titrations: Acid base concepts, Role of solvents, Relative strengths of acids and bases, Ionization, Law of mass action, Common ion effect, Ionic product of water, pH, Hydrolysis of salts, Henderson-Hasselbach equation, Buffer solutions, Neutralization curves, Acid-base indicators, Theory of indicators, Choice of indicators, Mixed indicators, Polyprotic systems, Polyamine and amino acid systems, Amino acid titrations; Oxidation Reduction Titrations: Concepts of oxidation and reduction, Redox reactions, Strengths and equivalent weights of oxidizing and reducing agents, Theory of redox titrations, Redox indicators, Cell representations, Measurement of electrode potential, Oxidation-reduction curves, Iodimetry and Iodometry, Titrations involving cerric ammonium sulphate, potassium iodate, potassium bromate, potassium permanganate; titanous chloride, stannous chloride and Sodium 2, 6-dichlorophenolindophenol; Precipitation Titrations: Precipitation reactions, Solubility product, Effect of acids, temperature and solvent upon the solubility of a precipitate, Argentometric titrations and titrations involving ammonium or potassium thiocyanate, mercuric nitrate, and barium sulphate, indicators, Methods of end point determination (GayLussac method, Mohr's method, Volhard's method and Fajan's method). Gravimetric Analysis: Precipitation techniques, The colloidal state, Supersaturation, Co-precipitation, Post-precipitation, Digestion, washing of the precipitate, Filtration, Filter papers and crucibles, Ignition, Thermogravimetric curves, Specific examples like barium sulphate, aluminium as aluminium oxide, calcium as calcium oxalate and magnesium as magnesium pyrophosphate, Organic precipitants; Non-aqueous titrations: Acidic and basic drugs, Solvents used, Indicators; Complexometric titrations; Complexing agents used as titrants, Indicators, Masking and demasking; Miscellaneous Methods of Analysis: Diazotization titrations, Kjeldahl method of nitrogen estimation, Karl-Fischer aquametry, Oxygen flask combustion method, Gasometry; Extraction procedures including separation of drugs from excipients; Potentiometry: Standard redox potential, Nernst equation, Half-cell potential, Standard and indicating electrodes, potentiometric titrations; Conductometry: Specific and equivalent conductance, conductometric titrations; Coulometry: Coulomb's law, Coulometric titrations at fixed potential/current; Polarography: Decomposition potential, Half-wave potential, Diffision/migration/migration current, Ilkovic equation, Cathodic/anodic polarography, Dropping mercury electrode, Graphite electrode, Organic polarography; Amperometry: Rotating platinum electrode, Amperometric titrations; Chromatography: Theory of chromatography, plate theory, Factors affecting resolution, van Deemter equation, The following chromatographic techniques (including instrumentation) with relevant examples of Pharmacopoeial products: TLC, HPLC, GLC, HPTLC, Paper Chromatography and Column Chromatography; The Theoretical Aspects, Basic Instrumentation, Elements of Interpretation of Spectra, and Applications (quantitative and qualitative) of the Following Analytical Techniques: Ultraviolet and visible spectrophotometry, Fluorimetry, Infrared spectrophotometry, Nuclear Magnetic Resonance spectroscopy, Mass Spectrometry (EI & CI only), Flame Photometry, Atomic Absorption Spectroscopy, X-ray Diffraction Analysis, Radioimmunoassay. Quality assurance: GLP, ISO 9000, TQM, Quality Review and Quality documentation, Regulatory control, regulatory drug analysis, interpretation of analytical data, Validation, quality audit: Quality of equipment, validation of equipment, validation of analytical procedures.