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1、Unit 2 Pharmacology,assess the effect of different doses on therapeutic effect use animal models to screen chemicals with anti-tumor activity measure plasma half life of a drug in body evaluate toxicity of a candidate drug in men determine the minimum inhibitory concentration of an antibiotic evalua
2、te the inhibitory effect of a candidate drug on an enzyme,History,1.Pharmacology studies the effects of drugs and how they exert their effects. E.g. penicillin kills susceptible bacteria by specifically inhibiting the transpeptidase(转肽酶) that catalyzes the final step in cell wall biosynthesis, the c
3、ross-linking of peptidoglycan（肽聚糖）.,E.g. acetylsalicylic acid（aspirin） Phospholipids phospholipase arachidonic acid(花生四烯酸） cyclooxygenase(环氧化酶) prostaglandin(前列腺素) inflammation,Inhibit the activity of COX,Enzyme inhibitor 32.4% Transport protein inhibitor 16.0% Receptor agonist 9.1% Receptor antagon
4、ist 10.7% Drugs acting on ion channels 9.1% DNA, RNA/ribosome,Typically a drug target is a key molecule involved in a particular metabolic or signaling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen. A survey in 2000 indicated
5、that:,2. Important figures in the development of pharmacology Friedrich Wohler Synthesis of urea(尿素): organic compounds can be synthesized from inorganic materials Oswald Schmiedeberg His work primarily dealt with finding the correlation between the chemical structure of substances and their effecti
6、veness. a thesis on the measurement of chloroform（氯仿） in blood studied the pharmacology of chloroform and chloral hydrate（水合氯醛 ） publication of Outline of Pharmacology trained a number of preeminent scientists,Jacob Abel founded and chaired the first department of pharmacology in the United States a
7、t the University of Michigan isolation of epinephrine（肾上腺素）from adrenal gland isolation of histamine（组胺）from pituitary extract preparation of crystalline insulin（胰岛素） William Withering discoverer of digitalis（洋地黄） for the treatment of congestive heart failure（充血性心力衰竭）,Definitions,Pharmacology has be
8、en defined as an experimental science that studies changes brought about in vivo and in vitro by chemically acting substances, whether used for therapeutic purpose or not. In the broadest sense, pharmacology is the science of studying the effect of drugs on living organisms. It attempts to describe
9、the biological response produced by drugs and to define the underlying mechanisms by which the responses are generated.,Drugs: Broadly defined, a drug is a chemical substance that can alter or influence the responsiveness of a biological system. The action of a drug is mediated by a naturally occurr
10、ing process of the body. A drug either mimics, facilitate, or antagonizes a normally occurring phenomenon.,Classification of drugs: Drugs used to combat infection Selective toxicity is the ability of a chemical or drug to kill a microorganism without harming its host Chemotherapy, in its most genera
11、l sense, is the treatment of a disease by chemicals especially by killing micro-organisms or cancerous cells.,Drugs used to replace inadequacies of naturally occurring substance insulin: is a hormone that is central to regulating energy and glucose metabolism in the body. When insulin is absent, glu
12、cose is not taken up by body cells and accumulate, diabetes mellitus（糖尿病） will result. L-dopa: After passing though the blood brain barrier（血脑屏障）, it is enzymatically transformed into dopamine, the insufficiency of which will cause parkinsonism (帕金森症),Drugs that change regulation antihypertensives,
13、antianginals, diuretics, anticoagulants, analgesics, antipyretic, sedatives,birth contrl pills (contraceptives) Drugs to alter mood or behavior (psychoactive drug，精神药物) a chemical substance that crosses the blood-brain barrier and acts primarily upon the central nervous system where it alters brain
14、function, resulting in changes in perception, mood, consciousness, cognition, and behavior。,Drug at site of administration,Drug in plasma,Drug/metabolites in urine, feces, bile,Drug/metabolites in tissues,Absorption,Distribution,Excretion,Biotransformation,1.Pharmacokinetics(药物代谢动力学):,Scope,2. Pharm
15、acodynamics（药物效应动力学）: is the study of the physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action，including the correlation of their actions with concentrations as well as the relationship between the activity and the chemi
16、cal structure.,Dose-response curve(量效曲线),minimum effective dose maximum efficacy（最大效能） median effective dose slope（斜率）,Structure-activity relationship: the relationship between the chemical or three-dimensional structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism. This allows to modify the effect or the potency of a drug by changing its chemica
