2012留学生第38-39章.ppt

Combination of antibacterial agents 1. For greater effects To reduce AR 3. To reduce resistance 4. To enlarge antibacterial spectrum 1. Mechanism of Action ???????????????????????????????????????????????????????? ??????? ??????? (1) ?-lactamase (2) Trapping mechanism (3) Changes in PBPs (4) Changes in porins (5) Active Outflux (6) Lack of autolysins 2 . Drug-Resistant Mechanism Pharmacokinetics Absorption: Not stable in GI,less aborbed by PO. Thus，IM or IV 2. Distribution: outside of cell. BBB? 3. Elimination: Metabolism? Excretion? Milk Glomerular filtration(10%) and active tubular secretion(90%), unchanged form Antibacterial Spectrum 1. Most G+ Coccobacteria and some G+ Bacilli 2. Some G- Coccobacteria 3. Spirobacteria: G- 4. Actynomyces: G+ 5. Very few G- Bacilli Staphylococcus Aureus G+ Streptococci G + Leptospira G- Cell Wall Ads of Penicilin G 1. Hypersensitivity reactions Prevention： hypersensitive or not Skin test Treatment: Adrenaline injection sc or im or into heart 2. Herxheimer Reaction 3. Hemolytic anemia, leucopenia, thrombocytopenia, nephropathy, and neuropathy are rarely observed adverse reactions and are usually associated with high intravenous dosage. 4. Cardiac blood vessels: Na+, K+ Is Penicillin G enough? 1. We like Penicillin for oral use. 2. How to kill bacteria with Penicillin G Resistance? 3. How to kill G- Bacilli? 4. How to kill those without cell walls? 1. Methicillin, 新青霉素I 2. Oxacillin, 新青霉素II 3. Nafcillin, 新青霉素III Penicillin-resistant is gone? More effective than penicillin G? 一旦耐，全耐？ Ampicillin Amoxicillin Broad-spectrum Penicillins:PO Pseudomonas aeruginosa Carbenicillin Injection Only Cephalosporins Cefalexin, 头孢氨苄,PO Cefazolin, 头孢唑啉,INJ Cefladine, 头孢拉定,PO/INJ G+ strong, G- weak Kidney Toxicity Beta-Lactamase sensitive Cefuroxime,头孢呋辛，INJ Cefuroxime axetil,头孢呋辛酯。PO/INJ G+， G-， both strong Kidney tox