基础医学课件-药物效应动力学.pptVIP

1.4 Risk and its assessment (安全性评价) （1）Therapeutic index（治疗指数, TI） TI＝LD50/ED50， （2）Safety margin: LD5～ED95 or LD1～ED99 2- Dose-Effect Relationship Therapeutic index Safety margin 安全范围 Therapeutic index 3- Mechanisms of Drug Actions 3.1 Structure-Activity Relationship (构效关系) Both the affinity of a drug and its functional activity are determined by its chemical structure. Relatively minor modifications in the drug molecule may result in major changes in pharmacological properties. Atropine 阿托品 Peripheral Central 中枢/外周 Scopolamine东莨菪碱Central 中枢 Anisodamine 山莨菪碱 Peripheral 外周 Norepinephrine去甲肾上腺素 ? receptor Epinephrine 肾上腺素 ?, ? receptors Isoprenaline 异丙肾上腺素 ? receptor 3.2 Non-specific mechanisms (非特异性机制) （1）Physioc-chemical reactions Antacids, mannitol, dextran, …… （2）Membrane-stablizing General anesthetics, ethanol, …… （3）Disinfectants 3- Mechanisms of Drug Actions 3.3 Specific mechanisms (特异性机制) (1) Receptor (受体) (2) Enzyme (酶) (3) Ion channel (离子通道) (4) Transporter (转运体) (5) Immune system (免疫系统) (6) Gene therapy (基因治疗) genetic engineering drugs (基因工程药物) (7) Others (其他) 3- Mechanisms of Drug Actions Specific mechanisms：Actions on cell functions Enzyme-targeting drugs Acetylcholinesterase inhibitor Cyclo-oxygenase inhibitor Angiotensin converting enzyme inhibitor Na+-K+-ATPase inhinitor H+-K+-ATPase inhinitor HMG-CoA reductase inhibitors Most of antibiotics and anti-tumor drugs Drugs acting on ion channels Furosemide inhibits Na+-K+-2Cl--transporter Neurotransmitter transporter inhibitors Targets of drug 4- Drug receptors Key events in the discovery and establishment of the concept of receptors 4- Drug receptors 4.1 Concept of receptors Receptor: the component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drug’s