Beta-lactam antibiotics Chapter 34 Beta-lactam antibiotics Shutcm-MBL 1

Classification of ß-lactam antibiotics 1. Penicillins; 2. Cephalosporins 3. Cephamycins 4. Monobactams 5. Carbapenems Shutcm-MBL

Classification of penicillins 1. Penicillin G (natural): water solution is not stable, i.m. or i.v. 2. Semisynthetic penicillins (1) ß-lactamase-resistant penicillins: e.g. oxacillin, flucloxacillin, diccloxacillin (2) The broad-spectrum penicillins (acid-resistant, can be taken orally) e.g. ampicillin, amoxicillin (3) Anti-pseudomonas penicillins e.g. Carbencillin, azlocillin (4) Anti gram-negative bacteria: e.g. mecillinam 假单胞菌 Shutcm-MBL

Pharmacokinetics of penicillin G Absorption: Oral F: 33.3%; Tmax: 30-60 min; Influencing factors: gastric acid, food, etc; Distribution: Widely throughout the body: liver, bile, kidney, semen, joint fluid, lymph, and intestine; cerebrospinal fluid (in meningitis) Excretion: Mainly by the kidney; T1/2: about 30 min 脑脊液 [,menin'dʒaitis] 脑(脊)膜炎 Shutcm-MBL

Spectrum of activity 1. Gram-positive cocci (Staphylococcus, streptococcus); 2. Gram-negative cocci (Neisseria meningitidis, neisseria gonorrhoeae); 3. Gram-positive bacilli (Clostridium perfringens, corynebacterium diphtheriae); 4. Spirochaeta (Treponema pallidum, leptospira); 5. Most anaerobe except Bacteriodes fragilis. [æ'nεərəub] 厌氧菌 Shutcm-MBL

Characteristics: bactericidal Mechanisms: (1) Bind to penicillin-binding proteins (PBPs), inhibit the activities of transpeptidase, resulting in interference with the peptidoglycan synthesis of bacterial cell wall; (2) Activate cell wall autolytic enzymes of bacteria, resulting in lysis and rupture of bacteria. Shutcm-MBL

Clinical uses 1. Gram-positive cocci infections • Pneumococcal pneumonia (大叶性肺炎）pharyngitis[.færin'dʒaitis](咽炎), amygdalitis [ə.migdə'laitis](扁桃体炎), bronchitis[brɑ:ŋ'kaitis] (支气管炎) , otitis [əu'taitis] media(中耳炎), suppurative ['sʌpjə.reɪtɪv] arthritis (化脓性关节炎), infectious endocarditis 细菌性心内膜炎, scarlet fever 猩红热 Shutcm-MBL

2. Gram-negative cocci infections • epidemic meningitis[ 2. Gram-negative cocci infections • epidemic meningitis[.menin'dʒaitis](流行性脑膜炎) • gonorrhoea[.gɔnə'ri:ə]淋病 3. Leptospira[leptəu'spaiərə]钩端螺旋体, syphilis ['sifilis]梅毒 4. Gram-positive bacilli infections • bacillus anthracis炭疽杆菌 • diphtheriae白喉杆菌 Shutcm-MBL

Mechanisms of resistance 1. Production of β-lactamases that destroy the antibiotics; 2. Alterations in or acquisition of novel penicillin-binding proteins (PBPs); 3. Decreased entry and/or active efflux of the antibiotic. Shutcm-MBL

Adverse reactions Penillins are generally very specific and safe antibiotics. 1. Allergic reactions: rash, anaphylactic shock (0.05‰) Antigenic determinant: degradation products (penicilloic acid, products of alkaline hydrolysis) Prophylaxis and treatments: ① Ask allergic history; ② avoid taking with an empty stomach; ③ injection prepared right before use; ④ skin test; ⑤ observation; ⑥ medicine for emergency treatment: adrenaline, dexamethasone. [,ænəfi‘læktik]过敏性休克 Shutcm-MBL

2. Local reactions • intramuscular injection: inflamed, pain, induration scleroma • oral: diarrhea 3. Neurotoxicity: paralysis of lower extremity, convulsion 4. Herxheimer reactions Shutcm-MBL

Cephalosporins Shutcm-MBL

General description of cepholasporins Mechanism of action: Similar to that of penicillin; Mechanisms of resistance: Similar to that of penicillin; Pharmacokinetics : Absorption: absorbed readily after oral administration; Distribution: several cephalosporins penetrate into cerebrospinal fluid in sufficient concentration (in meningitis) Excretion: primarily by the kidney; Adverse reactions: Hypersensitivity reactions (identical to penicillins; cross-allergenicity between cepholasporins and penicillins); nephrotoxicity ( less than aminoglycosides or polymyxins); Shutcm-MBL

Classification of cephalosporins (by generations) Shutcm-MBL

3rd generation cepholasporins • Broader spectrum: effective to gram-negative bacterial infections • More resistant to β-lactamase • Less allergic reactions (compare with penicillin) To treat the infection which can’t be treat with Penicillin G Shutcm-MBL

β-Lactamase inhibitors Drugs: clavulanic acid, sulbactam, tazobactam Effects: potent inhibitors of (many but not all) β-lactamase but weak antibacterial action; Applications: be combined with penicillins to extend the spectrum of penicillins against β -lactamase-producing organisms. Shutcm-MBL