1 / 33

Inhibitors of cell wall synthesis (β-Lactam Antibiotics )

Inhibitors of cell wall synthesis (β-Lactam Antibiotics ). 1. PENICILLINS 2.Cephalosporins 3.Carbapenems ( Imipenem ) 4. Monobactams ( Aztreonam). Penicillins. Classification Narrow spectrum penicillins Antistaphylococcal penicillins Extended – spectrum penicillins.

peets
Download Presentation

Inhibitors of cell wall synthesis (β-Lactam Antibiotics )

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Inhibitors of cell wall synthesis (β-Lactam Antibiotics ) • 1. PENICILLINS 2.Cephalosporins • 3.Carbapenems ( Imipenem ) • 4. Monobactams ( Aztreonam)

  2. Penicillins Classification • Narrow spectrum penicillins • Antistaphylococcal penicillins • Extended –spectrum penicillins .

  3. Mechanism of action • Like all β-lactam antibiotics , inhibit the synthesis of bacterial cell wall . • They are bactericidal on the actively growing bacteria.

  4. Pharmacokinetics Absorption • Depending on acid stability • Absorption of most oral penicillins is impaired by food except amoxicillin .

  5. Metabolism & Excretion • Not metabolized • Excreted unchanged in urine • Probenecid blocks their secretion • Nafcillin is mainly cleared by biliary route • Oxacillin by both kidney & biliary route.

  6. Distribution • Relatively insoluble in lipid • Poor penetration into cells and BBBInflammation permits entrance into CSF. • Proteins binding vary from 20%-90%

  7. Narrow spectrum penicillins Penicillin G • Short duration • Acid unstable • Penicillinase (β- lactamase ) sensitive • Used in infections caused by streptococci, meningococci, enterococci & non-β- lactamase – producing staphylococci.

  8. Phenoxymethyl penicillin (P. V) • Less effective than penicillin G • Acid stable • Penicillinase sensitive • Short acting ( four times/day) • Used in minor infections

  9. Procaine penicillin • Long acting (every 12 h ) . • Acid unstable ( I.M.I ) • Penicillinase sensitive • Used to prevent subacute bacterial endocarditis due to dental extraction or tonsillectomy in patients with congenital or acquired valve disease .

  10. Benzathine penicillin • Long acting (every 3-4 weeks ) • Acid unstable • Penicillinase sensitive • Treatment of β-hemolytic streptococcal . • Used as prophylaxis against reinfection with β- hemolytic streptococci to prevent rheumatic fever . • Once a week for 1-3 weeks for treatment of syphilis (2.4 million units I.M.)

  11. Penicillinase resistant to staphylococcal β-lactamase producer • Methicillin acid unstable • Nafcillin its absorption is erratic • Oxacillin, Cloxacillin,Dicloxacillin (acid stable ). • Used in minor & severe Stap. infections

  12. Extended spectrum penicillins • Aminopenicillins • Carboxypenicillins • Ureidopenicillins Retain the spectrum of Penicillin G, but having greater activity against gram –negative bacteria.

  13. Aminopenicillins(Ampicillin &Amoxicillin) Therapeutic uses • H. influenza infections • E. coli • Ampicillin ( not amoxicillin) is effective for shigellosis & complicated salmonella infections. • Prophylaxis of infective endocarditis • Urinary tract infections • Effective against penicillin –resistant pneumococci

  14. Carboxypenicillins(Ticarcillin)&Ureidopenicillin(Piperacillin)Carboxypenicillins(Ticarcillin)&Ureidopenicillin(Piperacillin) • Effective against pseudomonas aeruginosa & Enterobacter organisms. • Ampicillin , amoxicillin , ticarcillin & piperacillin are available in combination with β-lactamase inhibitors as clavulanic acid ,sulbactam or tazobactam.

  15. Adverse effects of penicillins • Hypersensitivity reactions • High dose in renal failure ---seizure • Naficillin (neutropenia) • Oxacillin (hepatitis) • Methicillin(nephritis) • Oral penicillins may lead to GIT upset. Ampicillin has been associated with pseudomembraneous colitis

  16. Cephalosporins First-Generation Cefazolin, Cephalexin, cephradin. • Are very effective against gram- positive cocci • Are given orally ,exceptcefazolin given I.V.I ,or I.M.

  17. Excretion & Distribution • Through kidney • Probenecid block tubular secretion and increase plasma level . • Can not cross B.B.B.

  18. Clinical uses • Urinary tract infections • Minor Staph.infections or minor polymicrobial infections as cellulitis or soft tissue abscess. • Cefazolin is the drug of choice for surgical prophylaxis, also as alternative to antistaph.penicillin in allergic patients .

  19. Second -Generations • Cefaclor ,Cefamandole, cefuroxime • Less active against gram-positive bacteria than first generation • Have extended gram –negative effect • No effect on P-aeruginosa or enterococci.

  20. Pharmacokinetics • Given orally or parentrally • Can not cross B.B.B. • Excreted through kidney

  21. Clinical uses • β -lactamase-producing H-influenza infections • Mixed anaerobic infections as peritonitis . • Community acquired pneumonia

  22. Third -Generations • Cefoperazone,Ceftazidime ,Ceftriaxone • Have extended gram- negative spectrum. • Some of them have an effect on P-aeruginosa (ceftazidime ) . • No effect on E-coli.

  23. Pharmacokinetics • Main route I.V.I. • Ceftriaxone has a long half- life (7-8h).can be given once every 24h. • Cross B.B.B. • Excreted through kidney .(Ceftriaxone & cefoperazonethrough bile ).

  24. Clinical uses • Serious infections • Cceftriaxone is first line for treatment of gonorrhea & drug of choice in meningitis. • P-aeruginosa infections ( ceftazidime ). • In penicillin-resistant pneumococci

  25. Fourth -Generations • Cefepime • More resistant to hydrolysis by β-lactamase • Active against P-aeruginosa & E-coli • Clinical use as third generations.

  26. Adverse Effects of cephalosporins • Allergy • Thrombophilibitis • Interstitial nephritis and tubular necrosis • Cephalosporins that contain a methylthiotetrazole group as cefamandole ,cefoperazonecause :hypoprothrombinemia & bleeding disorders

  27. Methylthiotetrazole ring causes severe disulfiram-like reaction ( alcohol or alcohol medication must be avoided ). • Superinfections. • Diarrhea.

  28. Carbapenems Imipenem • Bctericidal, inhibit bacterial cell wall synthesis. • Has a wide spectrum of activity • Resistant to most β lactamases except metallo-β lactamase .

  29. Pharmacokinetics • Not absorbed orally, taken by I.V.I. • Inactivated by dehydropeptidases in renal tubules, so it is given with an inhibitor cilastatin for clinical use. • Penetrates body tissues and fluids including C.S.F.

  30. Clinical uses • Mixed aerobic and anaerobic infections • Is the β lactam of choice for treatment of enterobacter infections. • Pseudomonal infections • Intrabdominal infections • Febrile neutropenic patient • Septicaemia.

  31. Meropenem • Highly active against gram-negative aerobes . • Not degraded by renal dehydropeptidase

  32. Adverse effects • Nausea, vomiting, diarrhea • Skin rash and reaction at the site of infusion • High doses in patients with renal failure may lead to seizures • Patients allergic to penicillins may be allergic to carbapenems .

  33. Monobactams Aztronam • Active only against gram-negative aerobic bacteria. • Given I.V. • Similar to β-lactam in mechanism of action • Penicillin-allergic patients tolerate aztronam • Skin rash & elevation of liver enzymes may occur

More Related