药理学讲义04 Drug Efficacy.ppt

Chapter 4Factors AffectingDrug Efficacy影响药效的因素 Main Factors Affecting Drug Efficacy Age 年龄1.1. Children 孩子们 1.2. The Elderly 老年人 2. Gender 性别 3. Genetic Factors 基因 4. Individual Variations 个体 5. Time of Administration 时间 6. Main Drug Interactions 相互作用 7. Tolerance 耐受性 8. Placebo Effects 无效对照剂 Double-Blind Trials Study Questions * * 1. Age 年龄 2. Gender 性别 3. Genetic Factors 基因 4. Individual Variations 个体 5. Time of Administration 时间 6. Drug Interactions 相互作用 7. Tolerance 耐药量 8. Placebo Effects 无效对照剂 The clearance of caffeine, a pattern observed for many drugs Metabolic clearance is weak during the first year of life The rule is: There is no rule Drugs are generally tested on young adults. Children doses cannot be determined by weight-adjustment of adult doses Times of great physiological changes (newborn, puberty) are the most unpredictable The US Food and Drug Administration (FDA) and the European Medicine Evaluation Agency (EMEA) encourage manufaturers to produce data for drug use on children –but large-scale clinical trials may not be required Hepatic blood flow and activities of cytochrome P450 enzymes are reduced, also at variable rates, but conjugation is relatively preserved Lipophilic drugs tend to have a greater Vd due to the increased ratio between body fat and lean mass, and the reduction of plasma protein binding In addition, the sensitivity to drugs and their adverse effects is increased, i.e. CNS-depressants, anticoagulants, etc. Renal clearance declines at variable rates to about 50% of young-adult values. It can be evaluated through a measure of creatinine clearance –a simple comparison between plasma levels and urine excretion of creatinine Lipophilic drugs tend to have a greater Vd in women Creatinine clearance is about 15% lower in women Hepatic activities of cytochrome P450 enzymes vary in both directions. For instance, women have more of the cytochrome CYP3A4, which metabolizes about 50% of all drugs There exist variations in cytochr