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 13

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:Clinical Pharmacogenetics Chapter:13 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 clinical pharmacogenetics,the purpose of clinical Teaching pharmacogenetics 2.Recognize the definition of single nucleotide polymorphisms and its Objectives; Teaching significance Requirements 3.Recognize the effects of CYP enzyme polymorphisms on drug metabolism 4.Master the ethnic differences and individual differences in clinical pharmacogenetics 1.Introduction to clinical pharmacogenetics 2.The purpose of clinical pharmacogenetics Teaching 3.The definition of single nucleotide polymorphisms and its significances Content 4.CYP enzymes phenotypes and effects 5.Case Report Teaching Teaching Focus:CYP enzymes phenotypes and effects. Focus; Difficult Problems:the concept and content of clinical pharmacogenetics, and how to use it in clinical practice Difficult Problems Solutions:Give examples of clinical drug use (the metabolic enzyme,the polymorphism and the effects)and the mechanisms of drug metabolism,the and their regulated dosage,and discuss about the rational drug therapy in patients Solutions according to its genotypes. Introduction to clinical pharmacogenetics 5min Time The purpose of clinical pharmacogenetics 5min Allotment SNPs and its significances 5min CYP phenotypes and effect 20min Pharmacogenetic principles and discuss 5min 1.The purpose of pharmacogenetics or pharmacogenomics Assignment 2.Single nucleotide polymorphism 3.Give an example to explain CYP2D6 genetic polymorphism and drug concentrations. 1.Principle of Clinical Pharmacology(Second Edition);Arthur J.Atkinson 2.Basic Clinical Pharmacology;Bertram G.Katzung Reference 3.Pharmacogenetics:from molecular to clinical;Zhou HongHao Text 4.Zhou,HH.Koshakji,RP.Silberstein,DJ.Wilkinson,GR.Wood,AJ Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites.N Engl J Med 1989;320,565-570

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: Clinical Pharmacogenetics Chapter: 13 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 clinical pharmacogenetics, the purpose of clinical pharmacogenetics 2. Recognize the definition of single nucleotide polymorphisms and its significance 3. Recognize the effects of CYP enzyme polymorphisms on drug metabolism 4. Master the ethnic differences and individual differences in clinical pharmacogenetics Teaching Content 1. Introduction to clinical pharmacogenetics 2. The purpose of clinical pharmacogenetics 3. The definition of single nucleotide polymorphisms and its significances 4. CYP enzymes phenotypes and effects 5. Case Report Teaching Focus; Difficult Problems and their Solutions Teaching Focus: CYP enzymes phenotypes and effects. Difficult Problems: the concept and content of clinical pharmacogenetics, and how to use it in clinical practice Solutions: Give examples of clinical drug use (the metabolic enzyme, the polymorphism and the effects) and the mechanisms of drug metabolism, the regulated dosage, and discuss about the rational drug therapy in patients according to its genotypes. Time Allotment Introduction to clinical pharmacogenetics 5min The purpose of clinical pharmacogenetics 5min SNPs and its significances 5min CYP phenotypes and effect 20min Pharmacogenetic principles and discuss 5min Assignment 1. The purpose of pharmacogenetics or pharmacogenomics 2. Single nucleotide polymorphism 3. Give an example to explain CYP2D6 genetic polymorphism and drug concentrations. Reference Text 1. Principle of Clinical Pharmacology (Second Edition); Arthur J. Atkinson 2. Basic & Clinical Pharmacology; Bertram G. Katzung 3. Pharmacogenetics: from molecular to clinical; Zhou HongHao 4. Zhou, HH. Koshakji, RP. Silberstein, DJ. Wilkinson, GR. Wood, AJ. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N Engl J Med 1989; 320,565-570

安微徽医科大学国际教育学院教案与讲稿 5.Ismail,R.Teh,LK.The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients.J Clin Pharm Ther 2006;31.99-109 6.Karas-Kuzelicki,N.Jazbec,J.Milek,M.Mlinaric-Rascan,I. Heterozygosity at the TPMT gene locus,augmented by mutated MTHFR gene,predisposes to 6-MP related toxicities in childhood ALL patients. Leukemia2009:23,971-974 7.Ingelman-Sundberg,M.Pharmacogenetics of cytochrome P450 and its applications in drug therapy:the past,present and future.Trends Pharmacol Sci2004;25,193-200 Memo 2

安徽医科大学国际教育学院教案与讲稿 2 5. Ismail, R. Teh, LK. The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. J Clin Pharm Ther 2006; 31. 99-109 6. Karas-Kuzelicki, N. Jazbec, J. Milek, M. Mlinaric-Rascan, I. Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood ALL patients. Leukemia 2009; 23, 971-974 7. Ingelman-Sundberg, M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 2004; 25, 193-200 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:Clinical Pharmacogenetics Chapter:13 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 clinical pharmacogenetics MODULE 2:The purpose of clinical pharmacogenetics MODULE 3:SNPs and its significances MODULE 4:CYP phenotypes and effect MODULE 5:Pharmacogenetic principles and discuss [INTRODUCTION TO CLINICAL PHARMACOGENETICSI 3min 1.PHARMACOGENETICS:the study of the role of inheritance in inter-individual variation in drug response. 2.PHARMACOGENOMICS:the use of DNA sequence information to measure and predict the reactions of individuals to drugs. 3.Paradox of Modern Drug Development [PURPOSE OF PHARMACOGENETICS AND PHARMACOGENOMICS] 5min 1.The purpose of pharmacogenetics and pharmacogenomics:Pharmacology+Genetics Genetic predisposition to drug effect Individualized pharmacotherapy:The right drug at right dose for the right people Revolutionize medicine 2.Factors Determining Interindividual variations in Drug Response. 3.Heritability of Drug Metabolism and Diseases. [SNPS AND ITS SIGNIFICANCES] 5min 1.Single nucleotide polymorphisms:is a DNA sequence variation occurring when a single nucleotide-A,T,C or G-in the genome (or other shared sequence)differs between members of a biological species or paired chromosomes in a human. A Key to Human Individuality+ A key to interindividual variations in drug metabolism and response 2.Genotypes of SNPs 3.Hierarchy of Pharmacogenetic Information from Single Nucleotide Polymorphisms 4.Variation in human genomics ICYP PHENOTYPES AND EFFECTI 20min 1.Drug-metabolizing enzyme genotype and plasma drug concentration 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: Clinical Pharmacogenetics Chapter: 13 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 clinical pharmacogenetics MODULE 2: The purpose of clinical pharmacogenetics MODULE 3: SNPs and its significances MODULE 4: CYP phenotypes and effect MODULE 5: Pharmacogenetic principles and discuss [INTRODUCTION TO CLINICAL PHARMACOGENETICS] 3min 1. PHARMACOGENETICS: the study of the role of inheritance in inter-individual variation in drug response. 2. PHARMACOGENOMICS: the use of DNA sequence information to measure and predict the reactions of individuals to drugs. 3. Paradox of Modern Drug Development. [PURPOSE OF PHARMACOGENETICS AND PHARMACOGENOMICS] 5min 1. The purpose of pharmacogenetics and pharmacogenomics:Pharmacology + Genetics
Genetic predisposition to drug effect
Individualized pharmacotherapy: The right drug at right dose for the right people
Revolutionize medicine 2. Factors Determining Interindividual variations in Drug Response. 3. Heritability of Drug Metabolism and Diseases. [SNPS AND ITS SIGNIFICANCES] 5min 1. Single nucleotide polymorphisms: is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in a human.
A Key to Human Individuality+
A key to interindividual variations in drug metabolism and response 2. Genotypes of SNPs 3. Hierarchy of Pharmacogenetic Information from Single Nucleotide Polymorphisms 4. Variation in human genomics [CYP PHENOTYPES AND EFFECT] 20min 1. Drug-metabolizing enzyme genotype and plasma drug concentration

安徽医科大学国际教育学院教案与讲稿 Poor Extensive Untrafast Drug-metabolizing enzyme genotype 2. Some drugs have such a wide therapeutic range that individualizing the dose is not important 3. Ethnic differences in mutant alleles produce ethnic differences in drug responses 4. Different ethnic populations may need different dose 5.High frequency of CYP2D6 variants in Caucasians Nortriptyfine dosing (mg) 50 150 500 Population-based dosing 00101 0.5 CYP2D6 CYP206 CYP2D6 CYP2D6 Homozygous Heterozygous Two normal Duplicated Deletion Deletion alleles Mutiplied Frameshift Frameshift Stop codons Stop codons 6.Case Report-CYP2D6 ultra rapid metabolizer 7.Metoprolol plasma concentration and CYP2D6 genetic polymorphism 100 Con ditference:60X 80 70 60 50. 20 14.2 40 13 39 UM EM EM/het. 100 100 Dose [mg] 8.High frequency of CYP2C19 variants in Chinese 9 TGN accumulation and 6-MP toxicity related to TPMT genotype 1D 0 m/m mw whw [PHARMACOGENETIC PRINCIPLES AND DISCUSS] 5min 1.Genetic tests identify DNA mutations of childhood leukemia.enabling physicians to choose the treatment that fits it precisely 2. Pharmacogenetic Principles 4

安徽医科大学国际教育学院教案与讲稿 4 2. Some drugs have such a wide therapeutic range that individualizing the dose is not important 3. Ethnic differences in mutant alleles produce ethnic differences in drug responses 4. Different ethnic populations may need different dose 5. High frequency of CYP2D6 variants in Caucasians 6. Case Report -CYP2D6 ultra rapid metabolizer 7. Metoprolol plasma concentration and CYP2D6 genetic polymorphism 8. High frequency of CYP2C19 variants in Chinese 9. TGN accumulation and 6-MP toxicity related to TPMT genotype [PHARMACOGENETIC PRINCIPLES AND DISCUSS] 5min 1. Genetic tests identify DNA mutations of childhood leukemia, enabling physicians to choose the treatment that fits it precisely. 2. Pharmacogenetic Principles