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 One Introduction to Clinical Pharmacology

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:Introduction to Clinical Pharmacology Chapter:One Teacher's name:Professor Wei Wei Grade:2013 Department:Clinical Medicine.School of International Education Time:14:30-16:50 Date(D/M/Y):3/2/2016 Teaching 1.Recognize the concept of Clinical Pharmacology,the development of Objectives; clinical pharmacology,research contents of Clinical Pharmacology,and the Teaching career goals of clinical pharmacologists Requirements 2.Recognize the important history events of modern pharmacology Teaching Introduction to Clinical Pharmacology Content Teaching Teaching Focus:Scientific basis of drug use,development and evaluation. Difficult Problems:the concept and content of Clinical Pharmacology,and Focus; how to use it in clinical practice Difficult Solutions:Give examples of clinical drug use(the effect and toxicity events) Problems and the history of representative drug development,list the important history and their events of modern pharmacology,and discuss about the rational drug therapy in Solutions patients,especially in special populations. Definition of clinical pharmacology 5min Important history events of modern pharmacology 20 min Development of clinical pharmacology 25 min Time The relationship between health,disease and drug 15 min Allotment Clinical Pharmacokinetics 15 min Clinical Pharmacodynamics 15 min Hot spots in research of clinical pharmacology 10 min Discuss 15 min Assignment 1.The concept of Clinical Pharmacology 2.The development of clinical pharmacology 1.Principle of Clinical Pharmacology(Second Edition);ArthurJ.Atkinson Reference 2.Basic Clinical Pharmacology;Bertram G.Katzung Text 3.Oxford Textbook of Clinical Pharmacology and Drug Therapy;David Grahame-Smith,Jeffrey Aronson Memo

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: Introduction to Clinical Pharmacology Chapter: One Teacher’s name: Professor Wei Wei Grade: 2013 Department: Clinical Medicine, School of International Education Time: 14:30—16:50 Date (D/M/Y): 3/2/2016 Teaching Objectives; Teaching Requirements 1. Recognize the concept of Clinical Pharmacology, the development of clinical pharmacology, research contents of Clinical Pharmacology, and the career goals of clinical pharmacologists 2. Recognize the important history events of modern pharmacology Teaching Content Introduction to Clinical Pharmacology Teaching Focus; Difficult Problems and their Solutions Teaching Focus: Scientific basis of drug use, development and evaluation. Difficult Problems: the concept and content of Clinical Pharmacology, and how to use it in clinical practice Solutions: Give examples of clinical drug use (the effect and toxicity events) and the history of representative drug development, list the important history events of modern pharmacology, and discuss about the rational drug therapy in patients, especially in special populations. Time Allotment Definition of clinical pharmacology 5 min Important history events of modern pharmacology 20 min Development of clinical pharmacology 25 min The relationship between health, disease and drug 15 min Clinical Pharmacokinetics 15 min Clinical Pharmacodynamics 15 min Hot spots in research of clinical pharmacology 10 min Discuss 15 min Assignment 1. The concept of Clinical Pharmacology 2. The development of clinical pharmacology Reference Text 1. Principle of Clinical Pharmacology (Second Edition); ArthurJ. Atkinson 2. Basic & Clinical Pharmacology; Bertram G. Katzung 3.Oxford Textbook of Clinical Pharmacology and Drug Therapy; David Grahame-Smith, Jeffrey Aronson Memo

安微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:Introduction to Clinical Pharmacology Chapter:One Teacher's name:Professor Wei Wei Grade:2013 Department:Clinical Medicine,School of International Education Time:14:30-16:50 Date(D/M/Y):3/2/2016 Lecture Notes: [MODULES] 5min MODULE 1:Introduction to Clinical Pharmacology MODULE 2:Clinical Pharmacokinetics MODULE 3:Clinical Pharmacogenetics,Drug interactions,Drug toxicology MODULE 4:Assessment of Drug Effects MODULE 5:Principles of drug use for special populations MODULE 6:Drug Discovery Development JIMPORTANT HISTORY EVENTS OF MODERN PHARMACOLOGY 10min 1804:FW.Serturner separated morphine from opium poppy,which has a analgesic action with dogs. 1819:F.Magedie found that action site of strychnine was at spinal cord with frogs. 1878:J N.Langley raises the concept of receptor depending on different actions of atropine and carpiline for salivary secretion of cats(acetylcholine receptors). 1899:Prof.Hoffman from Bayer of Germany synthesized acetyl salicylic acid(ASA;aspirin).In 1971:John Vane found aspirin inhibited PGs synthesis. 1909:P.Ehrich gave a treatment of syphilis with neo-arsine-vitriolum,which started a new epoch of chemotherapy for infection diseases. 1928:A.Fleming investigated Penicillium and found phenomenon inhibiting bacteria. 1940:H W.Florey isolated penicillin,started the age of antibiotics. Early 1960:China scholar Dr.Gang ZHOU found that grey matter surrounding third ventricle in thalamuswas the analgesic site of morphine. [PARTIAL LIST OF GOLD AND MODELLACCOMPLISHMENTS] 4min 1937-INTRODUCED DOUBLE-BLIND TRIAL DESIGN 1939 Initiated CORNELL CONFERENCES ON THERAPY 1953-ANALYZED DIGOXIN EFFECT KINETICS TO ESTIMATE ABSOLUTE BIOAVAILABILITY AS WELL AS TIME-COURSE OF CHRONOTROPIC EFFECTS+ 1960-FOUNDED CLINICAL PHARMACOLOGY AND THERAPEUTICS IDEVELOPMENT OF CLINICAL PHARMACOLOGYI 5min In 1930s,the Concept of Clinical Pharmacology was introduced,which has become a independent subject. In 1970s,IUPHAR established the group of clinical pharmacology. 2

安徽医科大学国际教育学院教案与讲稿 2 Teaching Plan for International Students, AHMU Title of the course: Introduction to Clinical Pharmacology Chapter: One Teacher’s name: Professor Wei Wei Grade: 2013 Department: Clinical Medicine, School of International Education Time: 14:30—16:50 Date (D/M/Y): 3/2/2016 Lecture Notes: [MODULES] 5min MODULE 1: Introduction to Clinical Pharmacology MODULE 2: Clinical Pharmacokinetics MODULE 3: Clinical Pharmacogenetics, Drug interactions, Drug toxicology MODULE 4: Assessment of Drug Effects MODULE 5: Principles of drug use for special populations MODULE 6: Drug Discovery & Development [IMPORTANT HISTORY EVENTS OF MODERN PHARMACOLOGY] 10min 1804: FW. Serturner separated morphine from opium poppy, which has a analgesic action with dogs. 1819: F. Magedie found that action site of strychnine was at spinal cord with frogs. 1878: J N. Langley raises the concept of receptor depending on different actions of atropine and carpiline for salivary secretion of cats (acetylcholine receptors). 1899: Prof. Hoffman from Bayer of Germany synthesized acetyl salicylic acid (ASA; aspirin). In 1971: John Vane found aspirin inhibited PGs synthesis. 1909: P.Ehrich gave a treatment of syphilis with neo-arsine-vitriolum, which started a new epoch of chemotherapy for infection diseases. 1928: A. Fleming investigated Penicillium and found phenomenon inhibiting bacteria. 1940: H W. Florey isolated penicillin, started the age of antibiotics. Early 1960: China scholar Dr. Gang ZHOU found that grey matter surrounding third ventricle in thalamuswas the analgesic site of morphine. [PARTIAL LIST OF GOLD AND MODELL ACCOMPLISHMENTS] 4min 1937 - INTRODUCED DOUBLE-BLIND TRIAL DESIGN * 1939 - Initiated CORNELL CONFERENCES ON THERAPY 1953 - ANALYZED DIGOXIN EFFECT KINETICS TO ESTIMATE ABSOLUTE BIOAVAILABILITY AS WELL AS TIME-COURSE OF CHRONOTROPIC EFFECTS † 1960 - FOUNDED CLINICAL PHARMACOLOGY AND THERAPEUTICS [DEVELOPMENT OF CLINICAL PHARMACOLOGY] 5min In 1930s, the Concept of Clinical Pharmacology was introduced, which has become a independent subject. In 1970s, IUPHAR established the group of clinical pharmacology

安徽医科大学国际教育学院教案与讲稿 In 1980,the first international conference of clinical pharmacology and therapeutics(CPT)was convoked in London. In July,2008,the 9th international conference of clinical pharmacology and therapeutics(CPT) was convoked in Quebec.Canada. [CLINICAL PHARMACOLOGYI 2min THE STUDY OF INTERACTION BETWEEN DRUGS AND HUMANS IRESEARCH CONTENTS OF CLINICAL PHARMACOLOGYI 5min Clinical Pharmacodynamics Clinical Pharmacokinetics Bioavailability Toxicology Adverse Drug Reaction Clinical Trials Drug Interaction ITHE RELATIONSHIP BETWEEN HEALTH,DISEASE AND DRUGI 5min Health not only includes physiological one,but also psychological health and society health. Diseases can be caused by exterior factors,e.g.,bacteria invasion,and interior factors,e.g., weakness of body,genetic disease.Diseases may be treated with drugs,by which health returns. It should be stressed that drug treatment is bilateral,returning to health and/or producing ADR (A)Health (B)Disease (C)Drug Treatment COURSE FOCUS] 3min Scientific basis of drug use,development and evaluation NOT therapeutics Principles of drugs use ICAREER GOALS OF CLINICAL PHARMACOLOGISTSI 3min Optimize understanding and use of existing medicines Develop and evaluate new medicines [THALIDOMIDE PHOCOMELIA] 8min EXEMPLE:Thalidomide is a sedative drug introduced in the late 1950s that was used to treat morning sickness.It was sold from 1957 until 1961,when it was withdrawn after being found to be a cause of birth defects. Modern uses of thalidomide (trademarked as Thalomid,according to FDA Orange Book)include 3

安徽医科大学国际教育学院教案与讲稿 3 In 1980, the first international conference of clinical pharmacology and therapeutics (CPT) was convoked in London. In July, 2008, the 9th international conference of clinical pharmacology and therapeutics (CPT) was convoked in Quebec, Canada. [CLINICAL PHARMACOLOGY] 2min THE STUDY OF INTERACTION BETWEEN DRUGS AND HUMANS [RESEARCH CONTENTS OF CLINICAL PHARMACOLOGY] 5min Clinical Pharmacodynamics Clinical Pharmacokinetics & Bioavailability Toxicology & Adverse Drug Reaction Clinical Trials Drug Interaction [THE RELATIONSHIP BETWEEN HEALTH, DISEASE AND DRUG] 5min Health not only includes physiological one, but also psychological health and society health. Diseases can be caused by exterior factors, e.g., bacteria invasion, and interior factors, e.g., weakness of body, genetic disease. Diseases may be treated with drugs, by which health returns. It should be stressed that drug treatment is bilateral, returning to health and/or producing ADR. [COURSE FOCUS] 3min Scientific basis of drug use, development and evaluation NOT therapeutics Principles of drugs use [CAREER GOALS OF CLINICAL PHARMACOLOGISTS] 3min Optimize understanding and use of existing medicines Develop and evaluate new medicines [THALIDOMIDE PHOCOMELIA] 8min EXEMPLE: Thalidomide is a sedative drug introduced in the late 1950s that was used to treat morning sickness. It was sold from 1957 until 1961, when it was withdrawn after being found to be a cause of birth defects. Modern uses of thalidomide (trademarked as Thalomid, according to FDA Orange Book) include

安徽医科大学国际教育学院教案与讲稿 treating multiple myeloma in combination with dexamethasone,and erythema nodosum leprosum, with strict controls on its use to prevent birth defects. JFACTORS CONTRIBUTING TO ADRS] 5min 1.Inappropriate polypharmacy 2.Lack of clear therapeutic goals 3.Failure to attribute new symptoms or laboratory test results to therapy 4.Low priority given to studying ADRS 5.General ignorance of pharmacology [RATIONALE FOR PLASMA LEVEL MONITORINGI 6min PRESCRIBED DOSE ADHERENCE ABSORPTION MOST TISSUES NONSPECIFIC PLASMA BINDING PROTEIN FREE DISTRIBUTION BOUND BIOPHASE ELIMINATION RECEPTOR BINDING METABOLISM RENAL EXCRETION EFFECT [BASIC CONCEPT OF PHARMACOKINETICS] 8min Time-concentration time-effect relationship Parameters clinical significance: Tmax(peak time)&Cmax(peak concentration) Vd (volume of distribution) Ke (elimination rate constant)&t1/2 (half life) AUC (area under the curve) F (bioavailability) CL (clearance) Classical compartment model Time-concentration curve steady blood concentration of repeated and continuous administration RECEPTOR] 3min Nature of receptors: Can be defined as any biologic target macromolecule in cells that interacts specifically with extracelluar signal.(i.e.,IL-1 and IL-1 receptor) Classification of receptors: G(guanosine)-protein-coupled receptors(GPCRs):PGE2 and EPs Is an important family of receptors with over a hundred members cloned to date THERAPEUTIC EFFECTS OF DRUGSI 6min 4

安徽医科大学国际教育学院教案与讲稿 4 treating multiple myeloma in combination with dexamethasone, and erythema nodosum leprosum, with strict controls on its use to prevent birth defects. [FACTORS CONTRIBUTING TO ADRS] 5min 1.Inappropriate polypharmacy 2. Lack of clear therapeutic goals 3. Failure to attribute new symptoms or laboratory test results to therapy 4. Low priority given to studying ADRS 5. General ignorance of pharmacology [RATIONALE FOR PLASMA LEVEL MONITORING] 6min [BASIC CONCEPT OF PHARMACOKINETICS] 8min Time-concentration & time-effect relationship Parameters & clinical significance: Tmax (peak time) & Cmax (peak concentration) Vd（volume of distribution） Ke（elimination rate constant）& t1/2（half life） AUC（area under the curve） F（bioavailability） CL（clearance） Classical compartment model Time-concentration curve & steady blood concentration of repeated and continuous administration [RECEPTOR] 3min Nature of receptors: Can be defined as any biologic target macromolecule in cells that interacts specifically with extracelluar signal. (i.e., IL-1 and IL-1 receptor) Classification of receptors： G(guanosine) -protein-coupled receptors (GPCRs): PGE2 and EPs Is an important family of receptors with over a hundred members cloned to date. [THERAPEUTIC EFFECTS OF DRUGS] 6min

安微医科大学国际教育学院教案与讲稿 Etiological therapy Replacement therapy:thyroxine-thyroid hypofunction. Drugs for gene therapy:antisense gene therapy-cancer Immuno-therapy:CD20mab-RA Therapy by killing pathogens:penicillin-pneumonia. Symptomatic therapy:aspirin-pain [THE MECHANISAMS OF DRUGACTION] 7min Affecting receptors:atropine blocks Acetylcholine Receptor Affecting specific targets Enzyme as a target:aspirin inhibits cyclooxygenase Immune-system as a target:rituximab inhibits B cell via anti-CD20 DNA as a target:VEGF antisense inhibits VEGF of cancer [CLINICAL EVALUATION OF NEW DRUGSI 7min Clinical Trial(Phase I、Ⅱ、l、安) Phase I:To study the PK and tolerance of drugs in humans Phase II:To study the safety and efficacy of drugs in patients Phase III:To further study the safety and efficacy of drugs in patients with large number Phase安：Postmarket surveillance Bioequivalent test:whether or not equivalence of two drugs by principle of bioavailability [HOT SPOTS IN RESEARCH OF CLINICAL PHARMACOLOGYI 10min 1.pharmacogenetics and pharmacogenomics 2.drug transport and multidrug resistance 3.drug interaction and mechanism of action 4.PK/PD combination study 5.pharmacology in sex differences [POTENTIAL OF PHARMACOGENOMICS] 8min Non-responders and toxic responders:Treat with alternative drug or dose Responders and patients not predisposed to toxicity:Treat with conventional drug or dose 5

安徽医科大学国际教育学院教案与讲稿 5 Etiological therapy Replacement therapy: thyroxine — thyroid hypofunction. Drugs for gene therapy: antisense gene therapy—cancer Immuno-therapy: CD20mab— RA Therapy by killing pathogens: penicillin— pneumonia. Symptomatic therapy: aspirin— pain [THE MECHANISAMS OF DRUG ACTION] 7min Affecting receptors: atropine blocks Acetylcholine Receptor Affecting specific targets Enzyme as a target: aspirin inhibits cyclooxygenase Immune-system as a target: rituximab inhibits B cell via anti-CD20 DNA as a target: VEGF antisense inhibits VEGF of cancer [CLINICAL EVALUATION OF NEW DRUGS] 7min Clinical Trial（Phase I、II、III、Ⅳ) Phase I: To study the PK and tolerance of drugs in humans PhaseⅡ: To study the safety and efficacy of drugs in patients Phase III: To further study the safety and efficacy of drugs in patients with large number Phase : Ⅳ Postmarket surveillance Bioequivalent test: whether or not equivalence of two drugs by principle of bioavailability [HOT SPOTS IN RESEARCH OF CLINICAL PHARMACOLOGY] 10min 1. pharmacogenetics and pharmacogenomics 2. drug transport and multidrug resistance 3. drug interaction and mechanism of action 4. PK/PD combination study 5. pharmacology in sex differences [POTENTIAL OF PHARMACOGENOMICS] 8min Non-responders and toxic responders: Treat with alternative drug or dose Responders and patients not predisposed to toxicity: Treat with conventional drug or dose