Faculty of Science, Mahidol University

Transcription

1 1 Faculty of Science, Mahidol University Course Syllabus and Lesson Plan Principles of Drug Action (SCBM 451) Academic Year 2018 August 21 th September 13 th, 2018

2 Course code SCBM 451 Total credit 2 (2-0-4) Prerequisite - Course Description 2 Course Syllabus and Lesson Plan SCID 451 Principles of Drug Action Academic Year 2018 Principle of drug action, pharmacodynamics: how drug acts; mechanisms of drug action, drug-receptor interaction, concepts of time-effect and dose-response relationships, pharmacokinetics: how body handling the drug, fate of drugs in the body: absorption, distribution, excretion and metabolism, factors determine the time course of drug action, drug discovery and development, drugs affecting autonomic nervous system, disorders of autonomic nervous system Course Objectives After completing this course, students should be able to: 1. Explain the basic concept in pharmacodynamics 2. Describe pharmacokinetic concept and explain what the body does to the drug 3. Discuss how drugs are discovered and developed 4. Classify cholinergic and adrenergic drugs 5. Describe the pharmacological basis of therapy of diseases related to autonomic nervous system dysfunction Course-learning outcome Student achievement is measured and evaluated by the ability to 1. Describe the concept of pharmacodynamics and pharmacokinetics 2. Describe factors that affect drug effect 3. List and compare the strategy of drug discovery and process of drug development 4. Describe the effects of cholinergic and adrenergic drugs Teaching Methods Lectures (L), conference (C), assigned reading and presentation Teaching Media Lecture handout, text-books, e-book, multi-media, reading assignments

3 3 Recommended Textbooks 1. Katzung, BG. (2015) Basic and Clinical Pharmacology 13 th ed. Lange Medical (ebook available in Access medicine website) 2. Goodman & Gilman s. (2011) The Pharmacological Basis of Therapeutics 12 th ed. The Mc.Graw-Hill Companies, Inc (ebook available in Access medicine website) Student Assessment Student s performance are evaluated as follows : 1. Knowledge: Written examination 80% 2. Performance: Conference 20% Student achievement will be graded according to the faculty and university standard using the symbols: A, B+, B, C+, C, D+, D, and F using percent points (not T-scores). Grade A more than 80% B % B 70-74% C % C 60-64% D % D 50-54% F below 50% Students must attend more than 80% of lectures to be allowed to take the examination. Rubric score for conference participation (total = 15 points for each conference) Punctuality Listening Frequency of participation Course Co-ordinator : Inadequate (1 point) Arrival after 15 min Lack of interest or disrespect for others Need development (3 points) Late less than 15 min Sometimes displays lack of interest Satisfactory (5 points) On time/late less than 5 min Actively and respectfully listens to peers and instructor Not participate 1-2 times > 3 times Pornpun Vivithanaporn, Department of Pharmacology Tel pornpun.viv@mahidol.ac.th Instructors : Pharmacology Nathawut Sibmooh (NS) nathawut.sib@mahidol.ac.th Natthinee Jantaratnotai (NJ) natthinee.jan@mahidol.ac.th Pansakorn Tanratana (PT) pansakorn.tan@mahidol.ac.th Pornpun Vivithanaporn (PP) pornpun.viv@mahidol.ac.th Porntipa Korprasertthaworn (PK) porntipa.kor@mahidol.ac.th Lecture Room : Pr201, Preclinical building 272 Rama VI road, Phayathai, Ratchathewi, Bangkok, 10400

4 4 SCBM 451 Principles of Drug Action Academic Year 2018 Week Date Time Topics Lecturer 1 Tue 21-Aug-18 Thurs 23-Aug-18 2 Tue 28-Aug-18 Thurs 30-Aug-18 3 Tue 4-Sep-18 Thurs 6-Sep-18 4 Tue 11-Sep-18 Thurs 13-Sep-18 TA = Teaching assistant 9:00-9:30 Class introduction and organization PP 9:30-10:30 L1: Introduction to pharmacokinetics and pharmacodynamics 10:30-11:30 L2: Mechanism of drug action PT 13:00-14:00 L3: Ligand-receptor interaction PT 14:00-15:00 L4: Dose-response curve PT 15:00-16:00 Self study 9:00-10:00 L5: Pharmacokinetics I Vd & clearance NS 10:00-11:00 L6: Pharmacokinetics II Half-life & steady state NS 11:00-12:00 L7: Pharmacokinetics III Dosage calculation NS 9:00-10:00 L8: Adverse drug reaction and drug interaction PP 10:00-11:00 L9: Drug used in special population PP 11:00-12:00 L10: Pharmacogenomics PK 13:00-14:00 14:00-15:00 Conference 1: Pharmacokinetic calculation 15:00-16:00 Question and Answer NS, PP 9:00-10:00 L11: Drug discovery and development PP 10:00-11:00 11:00-12:00 9:00-10:00 10:00-11:00 11:00-12:00 Conference 2: Pharmacodynamics Mid-class exam (L1-L11 and conference 1-2) PK NS PT, PP PP, TA 13:00-14:00 L12: Introduction to ANS pharmacology PT 14:00-15:00 L13: Cholinergic agonists PT 15:00-16:00 L14: Cholinergic antagonists PT 9:00-10:00 L15: Skeletal muscle relaxant PP 10:00-11:00 L16: Adrenergic agonists NJ 11:00-12:00 L17: Adrenergic antagonists NJ 9:00-10:00 10:00-11:00 11:00-12:00 13:00-14:00 14:00-15:00 Conference 3: Integrative ANS pharmacology Conference 4: Organophosphate poisoning PT, PP PT, PP 15:00-16:00 Question and Answer PT, PP 9:00-10:00 10:00-11:00 11:00-12:00 Final-class exam (L12-L17 and conference 3-4) PP, TA

5 Lecture 1: Introduction to pharmacokinetics and pharmacodynamics Lecturer: Porntipa Korprasertthaworn, Ph.D., Department of Pharmacology Date/Time: Tue 21 August, 2018; Understand the fundamental concepts of pharmacokinetics and pharmacodynamics. 2. Describe sources of drug, dosage forms and routes of drug administration. 1. Introduction to pharmacokinetics and pharmacodynamics 2. Sources of drug, dosage forms and routes of drug administration 1. Lecture 50 min 2. Question and answer 10 min 1. Katzung BG. Introduction: The Nature of Drugs & Drug Development & Regulation. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e New York, NY: McGraw-Hill; Holford NG. Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e New York, NY: McGraw-Hill; Rivera SM, Gilman A. Drug Invention and the Pharmaceutical Industry. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill; 2018.

6 Lecture 2: Mechanism of drug action Lecturer: Pansakorn Tanratana, MD., Ph.D., Department of Pharmacology Date/Time: Tue 21 Aug, 2018; Discuss the mechanism of action of drugs. 2. Distinguish between the specificity of a drug action and the selectivity of a drug action. 3. Explain the types and molecular structure of receptors. 4. Explain the functional roles of receptors. 1. Mechanism of action of drugs 2. Types and molecular structure of receptors 3. Functional roles of receptors Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

7 Lecture 3: Ligand-receptor interaction Lecturer: Pansakorn Tanratana, MD., Ph.D., Department of Pharmacology Date/Time: Tue 21 Aug, 2018; Define the following terms: affinity, efficacy, potency, agonist, partial agonist, inverse agonist, antagonist, tachyphylaxis, desensitization, inactivation, refractory and down-regulation. 2. Describe the pharmacological events of agonist action. 3. Describe the pharmacological events of antagonist action. 1. Definition of affinity, efficacy, potency, agonist, partial agonist, inverse agonist, antagonist, tachyphylaxis, desensitization, inactivation, refractory and downregulation 2. Agonism and stimulus response mechanism General mechanism of agonism 3. Drug antagonism Type of antagonism Competitive and irreversible antagonism Noncompetitive antagonism Physiological antagonism Pharmacological antagonism Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

8 Lecture 4: Dose-response curve Lecturer: Pansakorn Tanratana, MD., Ph.D., Department of Pharmacology Date/Time: Tue 21 Aug, 2018; Understand the principal concepts of dose-effect relationship. 2. Distinguish between graded and quantal dose-response curve. 3. Define therapeutic and toxic effect of a drug. 4. Calculate therapeutic index of a drug. 1. Monitoring dose-effect relationship 2. Differences between graded and quantal dose-response curve 3. Therapeutic and toxic effect of a drug 4. Therapeutic index calculation Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

9 Lecture 5-7 : Pharmacokinetics I-III Lecturer Nathawut Sibmooh, MD., Ph.D., Department of Pharmacology Date/Time: Thurs 23 Aug 2018; Describe the processes of pharmacokinetics. 2. Discuss the importance of clearance and how it is measured. 3. Discuss the importance of volume of distribution and how it is measured. 4. Describe the importance of half-life, and its determinants. 5. Describe how drug is cleared by liver, and determinants of hepatic clearance. 6. Discuss the importance and determinants of bioavailability. 7. Describe how drug is cleared by kidneys, and determinants of renal clearance. Relationship between pharmacokinetics and pharmacodynamics ADME Clearance Volume of distribution Half-life and first-order kinetics Hepatic drug clearance Bioavailability and first-pass clearance Predicting drug interactions and the effects of disease states for metabolized drugs Clearance of drugs by kidneys Lecture 150 min Discussion (question and answer) 30 min 1. Jambhekar SS, Breen PJ. Editors, Basic pharmacokinetics. Pharmaceutical Press, Grayslake, Rowland M, Tozer TN. Editors, Clinical pharmacokinetics concepts and applications. 3 rd ed. Lippincott Williams & Wilkins, Pennsylvania,

10 Lecture 8: Adverse drug reaction and drug interaction Lecturer: Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Tue 28 Aug 2018; Categorize types of adverse drug reaction. 2. Discuss the effects of drug interaction on pharmacokinetic parameters, plasma drug concentration, effects and adverse drug reaction. 3. Discuss the problem and benefit of drug interaction. 1. Types of adverse drug reaction Excessive pharmacological effect Allergy 2. Types of drug interaction Pharmacokinetic drug interaction Pharmacodynamic drug interaction Lecture 25 min Interactive question and answer 25 min Summary 10 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc. 3. Brenner G.M. and Stevens C.W. (2012) Pharmacology. 4th ed. Philadelphia: Elsevier. 4. Rang H.P., Dale M.M., Ritter J.M. and Moore P.K. (2012) Pharmacology. 7th ed. Churchill Livingstone.

11 Lecture 9: Drug used in special population Lecturer: Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Tue 28 Aug 2018; Identify factors that affect drug effect in pregnant women, nursing mothers, pediatric and geriatric patients 2. List gender- and age-related pharmacokinetic and pharmacodynamic changes 3. Give examples of drug with different response and toxicity in each group of special population 1. Special population: pregnancy, nursing mother, pediatric, geriatric patients 2. Pharmacokinetic and pharmacodynamic factors to be considered in special population 3. Categorize the drug according to the adverse effects in pregnancy Summary 10 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc. 3. Rang H.P., Dale M.M., Ritter J.M. and Moore P.K. (2012) Pharmacology. 7th ed. Churchill Livingstone.

12 Lecture 10: Pharmacogenomics Lecturer: Porntipa Korprasertthaworn, Ph.D., Department of Pharmacology Date/Time: Tue 28 Aug 2018; Explain definition of pharmacogenomics 2. Describe types of gene mutations and their impact on drug response 3. Apply knowledge to explain or predict the effects of genetic variation in drug efficacy and toxicity 1. Overview of pharmacogenomics 2. Genetic variations in drug response 3. Clinical relevance of pharmacogenomics Question and answer 10 min 1. Relling MV, Giacomini KM. Pharmacogenetics. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13e. McGraw-Hill; Hibma JE, Giacomini KM. Pharmacogenomics. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e. McGraw-Hill; Rang HP, Ritter JM, Flower RJ and Henderson G. Individual Variation, Pharmacogenomics and Personalised Medicine, In: Rang & Dale s Pharmacology, 8e. Elsevier Ltd.; 2015.

13 Lecture 11: Drug discovery and development Lecturer: Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Thurs 30 Aug 2018; Discuss how drugs are discovered. 2. Discuss the principle of drug development. 3. List various steps involving in the development of new drugs. 4. List the difference between each step of drug discovery. 1. The drug discovery processes 2. The drug development process: Preclinical studies Clinical trials (phases I, II, III) Postmarketing surveillance (phases IV) Question and answer 10 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc.

14 Conference 1: Pharmacokinetic calculation Lecturer: Nathawut Sibmooh, MD., Ph.D., Department of Pharmacology Date/Time: Tue 28 Aug 2018; Calculate primary pharmacokinetic parameters. 2. Calculate loading and maintenance doses. 1. Cases with pharmacokinetic data and instruction. 2 hours of case discussion and calculation 1. Jambhekar SS, Breen PJ. Editors, Basic pharmacokinetics. Pharmaceutical Press, Grayslake, Rowland M, Tozer TN. Editors, Clinical pharmacokinetics concepts and applications. 3 rd ed. Lippincott Williams & Wilkins, Pennsylvania, Conference 2: Pharmacodynamics Lecturer: Pansakorn Tanratana, MD., Ph.D., Department of Pharmacology logy Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Tue 30 Aug 2018; Define the following terms: affinity, potency, efficacy, EC50, IC50, Kd, Bmax, ED50, LD50, therapeutic index 2. Explain basic concepts of concentration-effects relationships 3. Explain the quantitative aspects of drug-receptor interaction 4. Discuss graded dose-response relationship and its application 5. Discuss quantal dose response relationship and its application 6. Discuss drugs risk and benefit 1. Definition of the following terms: affinity, potency, efficacy, EC50, IC50, Kd, Bmax, ED50, LD50, therapeutic index 2. Monitoring of drug effects a. Time-effect relationship b. Dose-effect relationship 3. Quantitation of agonist-receptor interaction 4. Quantitation of antagonist-receptor interaction Presentation and group discussion 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc. 3. Rang H.P., Dale M.M., Ritter J.M. and Moore P.K. (2012) Pharmacology. 7th ed. Churchill Livingstone.

15 Lecture 12: Introduction to ANS pharmacology Lecturer: Pansakorn Tanratana, M.D., Ph.D., Department of Pharmacology Date/Time: Tue 4 Sep 2018; Describe the major divisions of the autonomic nervous system in term of anatomical and neurotransmitter features. 2. Describe central control of the autonomic nervous system. 3. Describe the pre- and post-synaptic regulation of cholinergic and adrenergic transmission. 4. Describe how autonomic control of target function is coordinately regulated. 1. Organization of the autonomic nervous system 2. Hypothalamus and autonomic nervous system 3. Comparison of anatomic and neurotransmitter features of the autonomic system 4. Neurotransmitter chemistry of the autonomic nervous system 5. Autonomic receptors 6. Functional organization of autonomic activity Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

16 Lecture 13: Cholinergic agonists Lecturer: Pansakorn Tanratana, M.D., Ph.D., Department of Pharmacology Date/Time: Tue 4 Sep 2018; Describe the spectrum and mode of actions of cholinoceptor-activating & cholinesterase-inhibiting drugs. 2. List clinical applications and toxicities of cholinoceptor-activating & cholinesteraseinhibiting drug. 1. Spectrum and mode of action of cholinoceptor-activating & cholinesteraseinhibiting drugs 2. Clinical pharmacology of cholinoceptor-activating & cholinesterase-inhibiting drugs Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

17 Lecture 14: Cholinergic antagonists Lecturer: Pansakorn Tanratana, M.D., Ph.D., Department of Pharmacology Date/Time: Tue 4 Sep 2018; Discuss pharmacodynamic and pharmacokinetic properties of muscarinic receptor-blocking drugs 2. List clinical applications of muscarinic receptor-blocking drugs 3. Discuss about cholinergic poisoning 1. Basic pharmacology of the muscarinic receptor-blocking drugs 2. Clinical pharmacology of the muscarinic receptor-blocking drugs 3. Basic and clinical pharmacology of the ganglionic-blocking drugs Question and answer 10 min 1. Rang, HP, Dale, MM, Ritter, JM and Moore, PK Pharmacology; Churchill Livingstone, 7th ed., Golan, D.E. (2012) Principles of pharmacology: The pathophysiologic basis of drug therapy, 3rd ed. Lippincott Williams & Wilkins

18 Lecture 15: Skeletal muscle relaxant Lecturer: Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Thurs 6 Sep 2018; Identify non-depolarizing neuromuscular blockers and depolarizing neuromuscular blocker 2. Describe the differences between depolarizing and non-depolarizing blockers in terms of their mechanisms of action and adverse effects. 3. Explain the differences between neuromuscular blocking drugs and spasmolytics 1. Neuromuscular transmission 2. Neuromuscular blocking drugs Non-depolarizing neuromuscular blocking drugs Depolarizing neuromuscular blocking drugs 3. Spasmolytic drugs Question and answer 10 min 1. Kruidering-Hall K, Campbell L. Skeletal muscle relaxants. In: Katzung BG, Trevor AJ, editors. Basic & clinical pharmacology. 13th ed. Singapore: McGraw-Hill; p Radhakrishman R, Whalen TB. Cholinergic antagonists. In: Whalen K, Finkel R, Panavelil TA, editors. Pharmacology Lippincott s illustrated reviews. 6th ed. Baltimore: Lippincott Williams & Wilkins; p Hibbs RE, Zambon AC. Agents acting at the neuromuscular junction and autonomic ganglia. In: Brunton LL, Chabner BA, Knollman BC, editors. Goodman & Gilman s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; p Brenner GM, Stevens CW. Acetylcholine receptor antagonists. In: Brenner GM, Stevens CW, editors. Pharmacology. 4th ed. Philadelphia: Elsevier; p

19 Lecture 16: Adrenergic agonists Lecturer: Nattinee Jantaratnotai, MD., Ph.D., Department of Pharmacology Date/Time: Thurs 6 Sep 2018; Discuss the physiological basis of adrenergic receptor functions 2. List the major actions of catecholamines and sympathomimetic drugs 3. List the major clinical applications of adrenergic agonists 4. Describe the clinical indications and toxicities of typical adrenergic agonists 1. Sympathetic nervous system and classification of adrenergic receptors 2. Chemistry and structure-activity relationship of sympathomimetic drugs 3. Pharmacological actions, adverse effects and clinical applications of -adernergic agonists -adrenergic agonists Question and answer 10 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc. 2. Katzung, B.G., Trevor A.J. (2015) Basic & Clinical Pharmacology 13th ed. McGraw- Hill Education.

20 Lecture 17: Adrenergic antagonists Lecturer: Nattinee Jantaratnotai, MD., Ph.D., Department of Pharmacology Date/Time: Thurs 6 Sep 2018; List the major actions of adrenergic antagonists 2. Compare the pharmacological/pharmacokinetic properties of nonselective and selective -blockers 3. Describe the clinical indications and toxicities of typical - and -antagonists 1. Classification and effects of - and -adrenergic antagonists 2. Pharmacological actions, adverse effects and clinical applications of - and - antagonists 3. Cautions and toxicities of administering - and -antagonists Question and answer 10 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc. 2. Katzung, B.G., Trevor A.J. (2015) Basic & Clinical Pharmacology 13th ed. McGraw- Hill Education.

21 Conference 3: Integrative ANS pharmacology Lecturer: Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Pansakorn Tanratana, M.D., Ph.D., Department of Pharmacology Date/Time: Tue 11 Sep 2018; To provide students an opportunity to assess their knowledge of autonomic nervous system pharmacology 2. To help students clarify their problems/questions from previous lectures and conferences 1. Cholinergic agonists and antagonists 2. Adrenergic agonists and antagonists 3. Skeletal muscle relaxant Practice questions 50 min Break 10 min Practice questions 50 min Break 10 min Practice questions 30 min Discussion (question and answer) 30 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc.

22 Conference 4: Organophosphate poisoning Lecturer: Pansakorn Tanratana, M.D., Ph.D., Department of Pharmacology Pornpun Vivithanaporn, Ph.D., Department of Pharmacology Date/Time: Tue 11 Sep 2018; Describe acute, chronic and delayed effects of organophosphate poisoning. 2. Explain the mechanism of action of drugs used in organophosphate poisoning treatment. 1. Mechanism of action of organophosphate compounds. 2. Mechanism of action of organophosphate antidotes: atropine and 2PAM. Small group discussion 120 min 1. Goodman & Gilman s (2011) The Pharmacological Basis of Therapeutics 12th ed. The McGraw-Hill Companies, Inc.