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1、 Unit 2 Pharmacology assess the effect of different doses on therapeutic effectuse 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 enzymeHistory1.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 cros
3、s-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 COXEnzyme inhibitor 32.4% Transport protein inhibitor 16.0% Receptor agonist 9.1% Receptor antagonist
4、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 that
5、:Jacob Abel founded and chaired the first department of pharmacology in the United States at 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
6、地黄) for the treatment of congestive heart failure(充血性心力衰竭) Definitions Pharmacology has been 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
7、 the science of studying the effect of drugs on living organisms. It attempts to describe the biological response produced by drugs and to define the underlying mechanisms by which the responses are generated. Classification of drugs: Drugs used to combat infection Selective toxicity is the ability
8、of a chemical or drug to kill a microorganism without harming its host Chemotherapy, in its most general sense, is the treatment of a disease by chemicals especially by killing micro-organisms or cancerous cells. bacteria Humanspenicillincell wall biosynthesiswithout cell wallsulfa drugs(磺胺药物)folic
9、acid synthesisthe synthetic pathway is not needed 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, glucose is not taken up by body cells and accumulate, diabetes
10、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, antianginals, diuretics, anticoagulants, analgesics, antipyr
11、etic, 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 function, resulting in changes in perception, mood, consciou
12、sness, cognition, and behavior。 2. Pharmacodynamics(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 relatio
13、nship between the activity and the chemical structure.Dose-response curve(量效曲线) minimum effective dose maximumefficacy(最大效能) median effective dose slope(斜率) Preclinical pharmacology (animal pharmacology or comparative pharmacology ) Pharmacological studies of candidate drugs in animal systems to pro
14、vide evidence of their potential activity, serving as predictors of human responses with the goals of assuring safety and effectiveness in humans Clinical pharmacology: is the science of drugs and their clinical use. It is underpinned by the basic science of pharmacology, with added focus on the app
15、lication of pharmacological principles and methods in the real world. It connects the gap between medical practice and laboratory science. The main objective is to promote the safety of prescription, maximize the drug effects and minimize the side effects Pharmacotherapeutics(药物治疗学): the use of drug
16、s in the prevention and treatment of disease.Toxicology: the aspect of pharmacology thatdeals with the adverse effects of drugsTranslation1. While the medicinal/organic chemist may create the candidate compound (sometimes referred to as a new chemical entity, NCE), it is the pharmacologist who is re
17、sponsible for testing it for pharmacological activity .2.Through research we now know that penicillin can disrupt the synthesis of cell wall in susceptible bacterial strains by inhibiting a key enzyme, while ASA can inhibit the action of human cell membrane enzyme known as cyclooxygenase.3. Structure-activity relationships are an integral link in the analysis of drug action, and exploitation of these relationships among established therapeutic agents has often led to the de
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