1. Beta-lactam antibiotics
Chapter 34
Beta-lactam antibiotics
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2. Classification of ß-lactam antibiotics
1. Penicillins;
2. Cephalosporins
3. Cephamycins
4. Monobactams
5. Carbapenems
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3. 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
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4. Pharmacokinetics of penicillin G
Absorption: Oral F: 33.3%; Tmax: 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
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5. 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
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6. 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.
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7. 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
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8. 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
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9. 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.
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10. 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
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11. 2. Local reactions • intramuscular injection: inflamed, pain, induration scleroma • oral: diarrhea 3. Neurotoxicity: paralysis of lower extremity, convulsion 4. Herxheimer reactions
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12. Cephalosporins
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13. 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);
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14. Classification of cephalosporins (by generations)
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15. 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
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16. 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.
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