安徽医科大学：《临床药理学 Clinical Pharmacology》课程教学资源（课件讲稿，英文版）Clinical Pharmacogenetics Drug interaction Drug toxicology（主讲：常艳）

Outlines Clinical Pharmacogenetics Drug toxicity and adverse drug reactions ■Drug interactions ■Homework

Outlines
Clinical Pharmacogenetics
Drug toxicity and adverse drug reactions
Drug interactions
Homework

Clinical Pharmacogenetics

Clinical Pharmacogenetics

Case report 1 Case report 2 ● 62 y.0.man hospitalized 56 y.o.man hospitalized for pneumonia with cough for hypertension ● Treated with“standard” doses of Codeine as a “Ordinary”Metoprolol (B1 adrenergic receptor inhibitor) cough suppressant 20mg bid ● Coma Morphine levels 20X Blood pressure not expected levels decrease

Case report 1 62 y.o. man hospitalized for pneumonia with cough Treated with “standard” 56 y.o. man hospitalized for hypertension “Ordinary ” Metoprolol Case report 2 Treated with “standard” doses of Codeine as a cough suppressant Coma Morphine levels 20 × expected levels “Ordinary ” Metoprolol (β1 adrenergic receptor inhibitor) 20mg bid Blood pressure not decrease

Factors Determining Interindividual Variations in Drug Response High/Body weight Genetic factors Sex Environmental Factors Age 白 iet/Smoking Elderly Comedications Children Interindividual Neonates Variability in Drug Response Disease Process Organ function 个 Liver,Kidney,Cardiac Concomitant Disease

Factors Determining Interindividual Variations in Drug Response Sex High/Body weight Environmental Genetic factors Age Elderly Children Neonates Concomitant Disease Disease Process Organ function Liver, Kidney, Cardiac Environmental Factors Diet / Smoking / Comedications Interindividual Variability in Drug Response

This is the individual difference. And the pharmacogenetics is to explain the reason of the individual difference

This is the individual difference. And the pharmacogenetics is to explain the reason of the individual difference

Definition ■PHARMACOGENETICS Pharmacology Genetics -the study of inherited genetic differ ences in drug metabolic pathway which ca n affect individual responses to drugs,both in terms of therapeutic effect as well as adv erse effects

PHARMACOGENETICS = Pharmacology + Genetics —— the study of inherited genetic differ Definition —— the study of inherited genetic differ ences in drug metabolic pathway which ca n affect individual responses to drugs, both in terms of therapeutic effect as well as adv erse effects

Single nucleotide polymorphism (SNP) ___SNP is the most common form of genetic variation in the human genome A variation in a single nucleotide that occurs at a specific position in the genome A Key to Human Individuality Base mutation SNP A key to interindividual variations in drug 2 metabolism and response 430C>T(Arg144Cys) ·CAGCTAAC币 CYP2C9*2 A:Adenine T:Thymine G:Guanine No or decreased enzymatic activity C:Cytosine

Single nucleotide polymorphism (SNP)
A variation in a single nucleotide that occurs at a specific position in the genome
A Key to Human Individuality
A key to interindividual variations in drug ____SNP is the most common form of genetic variation in the human genome Base mutation metabolism and response A: Adenine T: Thymine G: Guanine C: Cytosine C A G C C C A A C T 5’ 3’ 430C>T (Arg144Cys) Arg144Cys) No or decreased enzymatic activity T CYP2C9*2

leu leu 8 8 glu Glutamate Lysine Normal Abnormal GC→AT→amino acid substitute→function change>drug metabolism and reaction

glu glu glu GAG C T C A A G T T C Glutamate Lysine Normal Abnormal G C→ A T amino acid substitute function change aadrug metabolism and reaction

The contents of pharmacogenetics Pharmacogenetics Drug Metabolizing Drug Drug Enzymes Transporters Targets Pharmacokinetics Pharmacodynamics Variability in Efficacy/Toxicity

Pharmacogenetics Drug Targets Drug Transporters Drug Metabolizing Enzymes The contents of pharmacogenetics Transporters Targets Pharmacokinetics Pharmacodynamics Variability in Efficacy/Toxicity

Drug metabolizing enzymes Widespread genetic polymorphism; According to their ability to metabolize drugs,they are classified as: UM,ultra-rapid metabolizer EM,extensive metabolizer IM,intermediate metabolizer PM,poor metabolizer

Widespread genetic polymorphism;
According to their ability to metabolize drugs, they are classified as： Drug metabolizing enzymes
UM, ultra-rapid metabolizer
EM, extensive metabolizer
IM, intermediate metabolizer
PM, poor metabolizer