Introductory Pharmacology

At the end of this course, students should be able to: 1. illustrate the history of pharmacology; 2. outline branches of pharmacology and their relevance to health professions and the drug industry; 3. enumerate sources of obtaining drug information and the origins of drugs; 4. list the various routes of drug administration, biological membranes crosses and transport mechanisms involved; 5. outline the components of pharmacokinetics and their influencing factors; 6. describe body compartments and their fluid volumes and drug binding sites; 7. explain the liver microsomal mixed function oxidase system, its phases and types of reactions and how drugs can induce/inhibit their activity; 76 8. outline the major routes of drug elimination and termination effects; 9. explain what first-pass effect is and mode of drug action; 10. discuss dose-effect relation of drugs including effects of the different ligand types and measurements of therapeutic index; 11. describe adverse drug reactions, dose-related, acute and chronic overdosage; 12. illustrate drug abuse and dependence, and the central mechanism of action of major drugs of abuse; 13. enumerate the signs and symptoms of overdose and withdrawal effects of major drugs of abuse, alcohol, opioids and benzodiazepines; and 14. explain the pharmacotherapeutic options and their relative benefits/side effects.

Definition, historical concepts and the development of modern pharmacology, therapeutics, clinical pharmacology and toxicology. Pharmacology in relation to the health professions. Medicine, pharmacy, dentistry, nursing. The role of pharmacology in the drug industry. Drug development, evaluation and control. Role of pharmacology in public health, social and preventive medicine. Information source. How to search for drug information, use of reference and cross–reference, book index, journals, list of useful reference books. Origin/source of drugs. Routes of administration of drugs. Biological membranes and transport of drugs, drug- body interaction. Pharmacokinetics, absorption, distribution, metabolism and elimination of drugs. Absorption and influencing factors. Drug distribution in the body compartment and fluid volumes, binding to plasma proteins, tissues and organs; passage into the CNS, passage across placenta. Biotransformation. Chemical pathways of drug metabolism, sites of biotransformation, liver microsomal mixed function oxidase system, Phase I and Phase II reactions, types of phases I, types of phase II reactions (glucuronidation, acetylation, glycine conjugation), inhibition, depression and induction of enzymes. Major routes of drug elimination and termination of effects (renal, biliary and faecal excretion), other minor routes (lungs, skin). Rates of drug absorption and elimination, measurements of clearance and apparent volume of distribution, factors influencing clearance and distribution, bioavailability, half-life, first pass effect. Use of pharmacokinetics in designing dosage regimes. Loading dose, maintenance dose. Clinical relevance of drug metabolism. Individual differences, drug-drug interactions, interaction between drugs and endogenous compounds. Factors affecting pharmacokinetics processes, disease, feeding status, age, sex. Pharmacodynamics. Mode of action of drugs. Molecular mechanism of drug action, drug receptor interactions, drugs acting on enzyme systems, non-specific interaction of drugs with living systems. Dose-effect relation of drugs. Dose-response curve, concentration-effect curve, potency, efficacy, therapeutic index, biological assay, effective dose (ED50), toxic dose (LD50), lethal dose (LD50), receptor binding of agonists and antagonists, competitive and non-competitive antagonists, partial agonist, receptor-effector coupling, spare receptors, other antagonism, chemical and physiological. Variability in individual response. Idiosyncrasy, pharmacogenetics, hypo-and hyper-reactivity, hypersensitivity, tolerance, tachyphylaxis. Adverse drug reactions, dose- related drug toxicity, acute and chronic over dosage. Drug dependence and addiction, underlying biological basis of addiction as a disease, differential diagnostic criteria for drug abuse vs. dependence and their differences, mechanism of action within the CNS of major drugs of abuse. Signs and symptoms of overdose caused by major drugs of abuse (including alcohol, opioids and benzodiazepines), signs and symptoms of opioid withdrawal, pharmacotherapeutic options for treatment of opioid abuse and dependence and their relative benefits and side effects; pharmacotherapeutic options for treatment of alcohol abuse and their relative benefits and side effects. Drug discovery and clinical trials, phases of clinical trials. Differences between single and double-blind designs for clinical trials. Definition of IND and NDA. Ways in which a clinical drug study is evaluated. 77