抗菌药物概论-张纬萍-2013-12-10.ppt

Chemotherapeutic Drugs Wei-Ping Zhang, PhD 张纬萍 Dept. of Pharmacology, School of Medicine, Zhejiang University weiping601@zju.edu.cn;General Considerationsfor chemotherapeutic drugs;Overview;The Birth of Modern Chemotherapy: Dreams of a “Magic Bullet”;Paul Ehrlich introduced an arsenic-containing chemical called salvarsan （阿斯凡纳明）to treat syphilis （梅毒） (1910). “Magic bullet” for treatment of syphilis ;History of Antimicrobial Therapy;History of Antimicrobial Therapy;History of Antimicrobial Therapy;II. Chemotherapeutic agents;;II. Chemotherapeutic agents;Ideal antimicrobial drugs;Antibacterial drugs (抗菌药) kill bacteria and arresting its growth antibiotics and synthetic antimicrobial agents such as sulfonamides(磺胺类) and quinolones (喹诺酮类).;Antibiotics（抗生素） Produced by various species of microorganisms (bacteria, fungi , actinomycetes) and semi-synthetic Suppress the growth of other microorganisms.;Antibacterial spectrum（抗菌谱） Narrow? Broad? Chemotherapetic index (CI)（化疗指数） CI= LD50 / ED50 CI= LD5 / ED95;TD50;Bacteriostatic drugs （抑菌药） inhibit the growth of microorganisms e.g. Sulfonamides, Tetracycline Bactericidal drugs （杀菌药） kill microorganisms e.g. Penicillin, Aminoglycosides;Bactericidal vs Bacterostatic杀菌药 vs 抑菌药;Minimum inhibitory concentration (MIC) 最低抑菌浓度 Minimum bactericidal concentration (MBC) 最低杀菌浓度 Post antibiotic effect (PAE) 抗生素后效应 Resistance （耐药性） Cross Resistance （交叉耐药性） First expose effect （首次接触效应）;II. Chemotherapeutic agents;最低抑菌浓度;;III. Mechanism of action;1. Inhibit synthesis of bacterial cell walls 2. Affecting permeability of cell membrane and leading to leakage of intracellular compounds 3. Inhibit protein synthesis 4. Affect bacterial nucleic acid metabolism 5. Block essential enzymes of folate metabolism ;Inhibiting synthesis of bacterial cell walls e.g. penicillins, b-lactams;III. Mechanism of action;2. Affecting permeability of membrane Ionic- sorbent （离子吸附剂） e.g. Aminoglycosides （氨基糖苷类） Binding to ergosterol （麦角固醇）