《药理学》课程教学课件（PPT讲稿）β-Lactam antibiotics

Chapter 32 B-Lactam antibiotics

Chapter 32 β-Lactam antibiotics

Amidase H H H A PENICILLIN 00 一N COOH Lactamase Substituted 6-aminopenicillanic acid O HH R1一C一N一C B A CEPHALOSPORIN 0 CH2一2 COOH Substituted 7-aminocephalosporanic acid

B-Lactam antibiotics are useful and frequently prescribed antibiotics that share a common structure mechanism of action-inhibition of synthesis of the bacterial cell wall peptidoglycan pharmacologic and clinical effects,and immunologic characteristics. 。 Important classes ofB-lactam antibiotics include penicillins,cephalosporin antibiotics,andB- lactamase inhibitors,et al. Bacterial resistance against theB-lactam antibiotics continues to increase at a dramatic rate.Mechanisms of resistance include not only production of B-lactamases,but also alterations in penicillin-binding proteins and decreased

• β-Lactam antibiotics are useful and frequently prescribed antibiotics that share a common structure ，mechanism of action—inhibition of synthesis of the bacterial cell wall peptidoglycan ， pharmacologic and clinical • effects, and immunologic characteristics. • Important classes ofβ-lactam antibiotics include penicillins, cephalosporin antibiotics, andβ- lactamase inhibitors, et al. • Bacterial resistance against theβ-1actam antibiotics continues to increase at a dramatic rate. Mechanisms of resistance include not only production of β-lactamases, but also alterations in penicillin-binding proteins and decreased

entry and active efflux of the antibiotics. B-Lactamase production is the most common mechanism of resistance. Penicillins [peni'sili:ns] penicillin G and V(belong to natural penicillins),which are highly active against susceptible Gram-positive cocci;

entry and active efflux of the antibiotics. β-Lactamase production is the most common mechanism of resistance. Penicillins [peni'sili:ns] penicillin G and V (belong to natural penicillins), which are highly active against susceptible Gram-positive cocci;

nafcillin,methicillin,oxacillin,cloxacillin,and dicloxacillin penicillinase-resistant penicillins),which are active against penicillinase-producing Staphylococcus aureus; ampicillin and other agents with an improved Gram-negative spectrum; Ticarcillin,carbenicillin and piperacillin. extended-spectrum penicillins with activity against Pseudomonas aeruginosa

nafcillin, methicillin, oxacillin, cloxacillin, and dicloxacillin（penicillinase-resistant penicillins） , which are active against penicillinase-producing Staphylococcus aureus; ampicillin and other agents with an improved Gram-negative spectrum; Ticarcillin，carbenicillin and piperacillin. extended-spectrum penicillins with activity against Pseudomonas aeruginosa

、CHg C-NH-CH-CH 1 Site of action of penicillinase 2 Site of action of amidase O=CN—CHC0OH A Thiazolidine ring Penicillins B B-Lactam ring Penicillinase Amidase RCH+NH2-CH-CH CHa O=CN一CHC00H O=C N-CH-COOH OH H R 6-Aminopenicillanic Acid Penicilloic Acids Fig 32-1 Chemical structure of penicillins

Fig 32-1 Chemical structure of penicillins

【Mechanism of action】 1.Penicillins inhibit the formation of cell walls Penicillins exerts its effect by binding to cellular receptors (Penicillin-binding proteins,PBPs, transpeptidation enzymes)>inhibiting transpeptidation reactions->interrupt the synthesis of cell wall peptidoglycan. 2.Penicillins also remove or inactivate an inhibitor of lytic enzymes (autolysin),resulting in lysis of microorganisms in an isotonic environment

【Mechanism of action】 1.Penicillins inhibit the formation of cell walls ： Penicillins exerts its effect by binding to cellular receptors （Penicillin-binding proteins,PBPs, transpeptidation enzymes） → inhibiting transpeptidation reactions → interrupt the synthesis of cell wall peptidoglycan. 2.Penicillins also remove or inactivate an inhibitor of lytic enzymes (autolysin), resulting in lysis of microorganisms in an isotonic environment

3 .In general,penicillin G is more effective against Gram-positive organisms than semi- synthetic penicillins. 【Pharmacokinetics penicillin G is rapidly destroyed at pH of gastric secretion. Penicillin G is widely distributed throughout the body,but dose not easily pass across the blood- brain barrier

３.In general, penicillin G is more effective against Gram-positive organisms than semi￾synthetic penicillins. 【Pharmacokinetics】 penicillin G is rapidly destroyed at pH of gastric secretion. Penicillin G is widely distributed throughout the body, but dose not easily pass across the blood￾brain barrier

Penicillin G is metabolized slightly by the liver and mainly is excreted by the kidney.Probenecid blocks the active tubular secretion of penicillin G and hence prolongs its action. long-acting forms such as penicillin G procaine and penicillin G benzathine are available for specific purposes. Semi-synthetic penicillins usually are absorbed more easily than penicillin G orally and they are excreted by both kidney and bile. Half-life of penicillin G is about 30 min,and much shorter than that of semi-synthetic penicillins

• Penicillin G is metabolized slightly by the liver and mainly is excreted by the kidney. Probenecid blocks the active tubular secretion of penicillin G and hence prolongs its action. • long-acting forms such as penicillin G procaine and penicillin G benzathine are available for specific purposes. • Semi-synthetic penicillins usually are absorbed more easily than penicillin G orally and they are excreted by both kidney and bile. • Half-life of penicillin G is about 30 min, and much shorter than that of semi-synthetic penicillins

[Antimicrobial activity and clinical use of penicillin G) These have the greatest activity against gram- positive organisms,gram-negative cocci,and non-B-lactamase-producing anaerobes. However,they have little activity against gram- negative rods.D They are susceptible to hydrolysis by B lactamases. Penicillin G may be used actively and prophylactically in the following cases:

【Antimicrobial activity and clinical use of penicillin G】 These have the greatest activity against gram￾positive organisms, gram-negative cocci, and non-β-lactamase-producing anaerobes. However, they have little activity against gram￾negative rods. They are susceptible to hydrolysis by β lactamases. Penicillin G may be used actively and prophylactically in the following cases：