安徽医科大学：《临床药理学 Clinical Pharmacology》课程教学资源（授课教案，英文版）Chapter 16 Drug Toxicity and Adverse Drug Reactions

安徽医科大学国际教育学院教案与讲稿 Teaching Plan for International Students,AHMU Title of the course:Drug Toxicity and Adverse Drug Reactions Chapter:16 Teacher's name: Qiong Huang Grade:2013 Department:Clinical Medicine,School of International Education Time:14:30-16:50 Date(D/M/Y):3/16/2016 1.Recognize the concept of adverse drug reaction and the impact of adverse Teaching drug reactions. Objectives; 2.Recognize the classification of adverse drug reactions. Teaching 3.Recognize the mechanism of drug toxicity. Requirements 4.Master the contexts of drug toxicity. 1.Introduction to adverse drug reaction. 2.The classification of adverse drug reactions. Teaching 3.The mechanism of drug toxicity. Content 4.The contexts of drug toxicity. 5.Questions and discussions. Teaching Teaching Focus:The mechanism of drug toxicity. Focus; Difficult Problems:the classification of adverse drug reactions,the Difficult mechanism of drug toxicity and how to use it in clinical practice Problems Solutions:Give examples of adverse drug reaction and the mechanisms of and their drug toxicity,and discuss about the rational drug therapy in patients. Solutions Introduction to adverse drug reaction 5min Time The classification of adverse drug reactions 10min The mechanism of drug toxicity 18min Allotment The contexts of drug toxicity 4min Questions and discussions 3min 1.The content of drug toxicity mechanism. Assignment 2 Give an example to explain side effect and possible mechanism. 1.Principle of Clinical Pharmacology(Second Edition);Arthur J.Atkinson 2.Basic Clinical Pharmacology;Bertram G.Katzung 3.Classen,DC.Pestotnik,SL.Evans,RS.Lloyd,JF.Burke,JP.Adverse drug events in hospitalized patients.Excess length of stay,extra costs,and Reference attributable mortality.JAMA 1997;277,301-306 Text 4.Lazarou,J.Pomeranz,BH.Corey,PN.Incidence of adverse drug reactions in hospitalized patients:a meta-analysis of prospective studies.N JAMA 1998,279,1200-1205. 5.Need,AC.Motulsky,AG.Goldstein,DB.Priorities and standards in pharmacogenetic research.Nat Genet 2005;37,671-681

安徽医科大学国际教育学院教案与讲稿 1 Teaching Plan for International Students, AHMU Title of the course: Drug Toxicity and Adverse Drug Reactions Chapter: 16 Teacher’s name: Qiong Huang Grade: 2013 Department: Clinical Medicine, School of International Education Time: 14:30—16:50 Date (D/M/Y): 3/16/2016 Teaching Objectives; Teaching Requirements 1. Recognize the concept of adverse drug reaction and the impact of adverse drug reactions. 2. Recognize the classification of adverse drug reactions. 3. Recognize the mechanism of drug toxicity. 4. Master the contexts of drug toxicity. Teaching Content 1. Introduction to adverse drug reaction. 2. The classification of adverse drug reactions. 3. The mechanism of drug toxicity. 4. The contexts of drug toxicity. 5. Questions and discussions. Teaching Focus; Difficult Problems and their Solutions Teaching Focus: The mechanism of drug toxicity. Difficult Problems: the classification of adverse drug reactions, the mechanism of drug toxicity and how to use it in clinical practice Solutions: Give examples of adverse drug reaction and the mechanisms of drug toxicity, and discuss about the rational drug therapy in patients. Time Allotment Introduction to adverse drug reaction 5min The classification of adverse drug reactions 10min The mechanism of drug toxicity 18min The contexts of drug toxicity 4min Questions and discussions 3min Assignment 1. The content of drug toxicity mechanism. 2 Give an example to explain side effect and possible mechanism. Reference Text 1. Principle of Clinical Pharmacology (Second Edition); Arthur J. Atkinson 2. Basic & Clinical Pharmacology; Bertram G. Katzung 3. Classen, DC. Pestotnik, SL. Evans, RS. Lloyd, JF. Burke, JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277, 301-306 4. Lazarou, J. Pomeranz, BH. Corey, PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. N JAMA 1998; 279,1200-1205. 5. Need, AC. Motulsky, AG. Goldstein, DB. Priorities and standards in pharmacogenetic research. Nat Genet 2005; 37, 671-681

安徽医科大学国际教育学院教案与讲稿 6.I Ralph Edwards,Jeffrey K Aronson.Adverse drug reactions:definitions, diagnosis,and management.Lancet 2000;356:1255-1259 7.Drug Toxicity.Cullen M.Taniguchi,Sarah R.Armstrong,Laura C.Green, David E.Golan,and Armen H.Tashjian,Jr.Lippincott Williams Wilkins. LP-FPPP-92900 R3 Memo 2

安徽医科大学国际教育学院教案与讲稿 2 6. I Ralph Edwards, Jeffrey K Aronson. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356: 1255–1259 7. Drug Toxicity. Cullen M. Taniguchi, Sarah R. Armstrong, Laura C. Green, David E. Golan, and Armen H. Tashjian, Jr. Lippincott Williams & Wilkins. LP-FPPP-92900 R3 Memo

安徽医科大学国际教育学院教案与讲稿 Teaching Plan for International Students,AHMU Title of the course:Drug Toxicity and Adverse Drug Reactions Chapter:16 Teacher's name:Qiong Huang Grade:2013 Department:Clinical Medicine,School of International Education Time:14:30-16:50 Date(D/M/Y):3/16/2016 Lecture Notes: [MODULES] 2min MODULE 1:Introduction to adverse drug reaction MODULE 2:The classification of adverse drug reactions MODULE 3:The mechanism of drug toxicity MODULE 4:The contexts of drug toxicity MODULE 5:Questions and discussions JINTRODUCTION TO ADVERSE DRUG REACTION] 3min 1.ADVERSE DRUG REACTION (ADR):a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis,diagnosis,or therapy of disease or for the modification of physiologic function. Side effects-minor unwanted effects of drugs Adverse Reaction-serious effects of drugs at therapeutic doses Toxicity-adverse drug event that occurs at high dose 2.IMPACT OF ADVERSE DRUG REACTIONS [THE CLASSIFICATION OF ADVERSE DRUG REACTIONS] 10min 1.Type A:Augmented pharmacologic effects dose dependent and predictable responsible for at least two-thirds of ADRs common,low mortality related to a pharmacological action of the drug 2.Type B:Bizarre effects dose independent and unpredictable uncommon,high mortality not related to a pharmacological action of the drug 3.Type C:Chronic effects dose-related and time-related associated with long-term use uncommon,involves dose accumulation 4.Type D:Delayed effects ·time-related uncommon,usually dose-related occurs or becomes apparent some time after the use of the drug 5.Type E:End-of-treatment effects 3

安徽医科大学国际教育学院教案与讲稿 3 Teaching Plan for International Students, AHMU Title of the course: Drug Toxicity and Adverse Drug Reactions Chapter: 16 Teacher’s name: Qiong Huang Grade: 2013 Department: Clinical Medicine, School of International Education Time: 14:30—16:50 Date (D/M/Y): 3/16/2016 Lecture Notes: [MODULES] 2min MODULE 1: Introduction to adverse drug reaction MODULE 2: The classification of adverse drug reactions MODULE 3: The mechanism of drug toxicity MODULE 4: The contexts of drug toxicity MODULE 5: Questions and discussions [INTRODUCTION TO ADVERSE DRUG REACTION] 3min 1. ADVERSE DRUG REACTION (ADR): a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.
Side effects – minor unwanted effects of drugs
Adverse Reaction – serious effects of drugs at therapeutic doses
Toxicity – adverse drug event that occurs at high dose 2. IMPACT OF ADVERSE DRUG REACTIONS [THE CLASSIFICATION OF ADVERSE DRUG REACTIONS] 10min 1. Type A: Augmented pharmacologic effects
dose dependent and predictable
responsible for at least two-thirds of ADRs
common, low mortality
related to a pharmacological action of the drug 2. Type B: Bizarre effects
dose independent and unpredictable
uncommon, high mortality
not related to a pharmacological action of the drug 3. Type C: Chronic effects
dose-related and time-related
associated with long-term use
uncommon, involves dose accumulation 4. Type D: Delayed effects
time-related
uncommon, usually dose-related
occurs or becomes apparent some time after the use of the drug 5. Type E: End-of-treatment effects

安微医科大学国际教育学院教案与讲稿 ●uncommon occurs soon after withdrawal of the drug 6.Type F:Failure of therapy common,dose-related unexpected failure of therapy often caused by drug interactions [THE MECHANISM OF DRUG TOXICITY] 18min 1."On-target"adverse effects:which are the result of the drug binding to its intended receptor, but at an inappropriate concentration,with suboptimal kinetics,or in the incorrect tissue niened urnengod X ·Dose too high 2."Off-target"adverse effects:which are caused by the drug binding to a target or receptor for which it was not intended 3.Production of toxic metabolites 95% glucuronidation total excreted acetaminophen and sulfation metabolites 5% OVERDOSE CYP450 ymesN-acetyl-benzoquinoneimine glutathione reacts with nucleophilic groups on Fulminant hepatotoxicity proteins to produce covalent protein and death derivatives 4. Production of harmful immune responses Type I hypersensitivity response(immediate hypersensitivity) Type II hypersensitivity response(antibody-dependent cytotoxic hypersensitivity) 。 Type IlI hypersensitivity response(immune complexmediated hypersensitivity) Type IV hypersensitivity response(delayed-type hypersensitivity) 5.Idiosyncratic responses ·rare adverse effects individual genetic differences in the response to the drug molecule 。difficult to predict [THE CONTEXTS OF DRUG TOXICITY] 4min 4

安徽医科大学国际教育学院教案与讲稿 4
uncommon
occurs soon after withdrawal of the drug 6. Type F: Failure of therapy
common, dose-related
unexpected failure of therapy
often caused by drug interactions [THE MECHANISM OF DRUG TOXICITY] 18min 1. “On-target” adverse effects: which are the result of the drug binding to its intended receptor, but at an inappropriate concentration, with suboptimal kinetics, or in the incorrect tissue 2. “Off-target” adverse effects: which are caused by the drug binding to a target or receptor for which it was not intended 3. Production of toxic metabolites 4. Production of harmful immune responses
Type I hypersensitivity response (immediate hypersensitivity)
Type II hypersensitivity response (antibody-dependent cytotoxic hypersensitivity)
Type III hypersensitivity response (immune complexmediated hypersensitivity)
Type IV hypersensitivity response (delayed-type hypersensitivity) 5. Idiosyncratic responses
rare adverse effects
individual genetic differences in the response to the drug molecule
difficult to predict [THE CONTEXTS OF DRUG TOXICITY] 4min

安徽医科大学国际教育学院教案与讲稿 1.Drug Overdose 2.Drug-Drug Interactions Pharmacokinetic Drug-Drug Interactions Pharmacodynamic Drug-Drug Interactions Drug-Herb Interactions [QUESTIONS AND DISCUSSIONSJ 3min 1.The content of drug toxicity mechanism. 2.Give an example to explain side effect and possible mechanism. 5

安徽医科大学国际教育学院教案与讲稿 5 1. Drug Overdose 2. Drug-Drug Interactions
Pharmacokinetic Drug-Drug Interactions
Pharmacodynamic Drug-Drug Interactions
Drug-Herb Interactions [QUESTIONS AND DISCUSSIONS] 3min 1. The content of drug toxicity mechanism. 2. Give an example to explain side effect and possible mechanism