中南大学 临床药理研究所 Pharmacology Chapter 1 Introduction About Pharmacology Chapter 2 Pharmacokinetics What the body does to a drug Chapter 3 Pharmacodynamics What a drug does to the body Chapter 4 Factor affecting drug efficacy How to use a drug rationally General Principles Chapter 1 Introduction What is pharmacology Pharmacology is the science Pharmacology is the science of studying the effect of drugs on of studying the effect of drugs on living organisms living organisms Scientific study of the Scientific study of the interactions between drugs and the interactions between drugs and the body body Drug Action and Mechanism Absorption Distribution Metabolism Excretion Pharmacodynamics PD Pharmacokinetics PK Drug body interaction What is drug A chemical substance that can modulate the current physiological status quo of a biological system A chemical which is utilized for the diagnosis prevention and cure of an unwanted health condition definition by FDA Ancient lNatural products Plants Animals Minerals Modern lActive principles of natural products lArtificial synthetics Full synthetic Semi synthetic Biological engineering Source of drugs Poppy Raw opium Opium tincture Morphine Codeine From natural product to active principles foxglove digoxin deadly nightshade atropine From natural product to active principles 1 Explore the pharmacokinetic and pharmacodynamic features of drugs 2 Probe the mystery of life process 3 Find and develop new drugs Missions of pharmacology The Long Road to a New Medicine Process of Drug Development synthesisScreen Phase II Clinical trial Phase III clinical trial Phase I clinical trial Animal PK PD Tox Dosage form Candidate chemicals Design Application Marketing History of medicines nPhase I Using natural products to treat diseases nChina Sheng Nong s Herbal Classic 神农本草经 described 365 TCM Compendium of Materia Medica 本草纲目 described 1892 TCM nGreeks e g Dioscorides De materia medica 药物 学 described 600 plants nIslamic physicians e g Avicenna Herbal medicine nPhase II Scientific nUsing pure drug compounds nUnderstanding physiopathology of diseases and pharmacology of drugs 1 Francois Magendie 1783 1855 a French physiologist Experimental procedures with animals for determination of drug action 2 Fredrick Surturner 1783 1841 isolated the chief alkaloid of opium Morphine pure chemicals and repeated quantitatively 3 Claude Bernard 1813 1878 investigated the plant extract curare and proposed a site of action for this agent 4 Rudolph Buchheim 1820 1879 In 1847 established the first laboratory in the basement of his home in Dorpat which is the cradle of experimental pharmacology 5 Oswald Schmiedeberg 1838 1921 In 1872 set up an institute of pharmacology in Strasbourg which became a mecca for training in pharmacology Modern pharmacology originated in Europe History of pharmacology Chapter 2 Pharmacokinetics Why do me need to know PK Optimize drug therapy to obtain a predictable response 1 Drug of choice 2 How much 3 How often 4 For how long The dose makes medicine Paracelsus 1538 Therapeutic Goal is to Achieve drug concentrations at the site of action target tissue that are sufficiently high enough to produce the intended effect without producing adverse drug reactions Drug Administration Drug Concentration in Systemic Circulation Drug in Tissues of Distribution Drug Metabolism or Excreted Drug Concentration at Site of Action Pharmacologic Effect Clinical Response ToxicityEfficacy PharmacokineticsPharmacodynamics Absorption DistributionElimination Drug at absorption site Metabolites Excreted drug Drug in body Time of dose 20 40 60 80 100 Section 1 Ch 2 Drug Transport Drug Transport Transfer of drugs across Membranes Filtration Aqueous diffusion Extracellular Intracellular Simple diffusion Lipid diffusion Carrier mediated transport 1 Active transport 2 Facilitated diffusion