内酰胺类抗生素（英文ppt）lactam

-Lactam Antibiotics n1. PENICILLINS 2.Cephalosporins n 3.Carbapenems ( Imipenems ) n 4. Monobactams ( Aztreonam) Penicillins nClassification nNarrow spectrum penicillins nAntistaphylococcal penicillins nBroad spectrum penicillins nExtended spectrum penicillins ( antipseudomonal penicillins). Mechanism of action nLike all -lactam antibiotics , inhibit the synthesis of bacterial cell wall . nThrough inhibition transpeptidase enzyme nThey are bactericidal on the actively growing bacteria. Pharmacokinetics nAbsorption nDepending on acid stability nAbsorption of most oral penicillins is impaired by food except amoxicillin . Metabolism doxycycline &minocycline n(16-18h once daily ). nIntermediate (12h) demeclocycline Short acting (6- 8h)oxy,tetracyclines. nClinical uses: nMycoplasma pneumonia nChlamydial infections nRickettsial infections nSpirocates nBrucellosis nAnthrax Clinical uses nCholera nTraveller,s diarrhea nHelicobacter pylori nAcne(minocycline&doxycycline) nBronchitis nProtozoal infections nMinocycline to eradicate meningococci carrier Not used in: nStreptococcal & staphylococcal infections . nGonococcal infections nMeningococcal infections nTyphoid fever Adverse effects nI.M.(pain & inflammation) nI.V.(thrombophilbitis) nGastric upset (N.,V.,D.) nEnterocolitis nSuper infections nDamage growing bone &teeth. Adverse effects nYellowish brown discolorationof teeth &dental caries. nLiver toxicity nKidney toxicity (tubular necrosis). nPhotosensitization(demeclocycine) nVestibular reaction(vertigo,dizziness,) n(Doxycycline &minocycline). Contraindications nWith milk or its products,or antacids. nPregnancy nChildren under 8 years. Chloramphenicol nBroad spectrum antibiotics nBacteriostatic,inhibits protein synthesis by binding to 50S ribosomal subunits. nRapidly &completely absorbed nRapidly distributed nCross placental barrier &B.B.B. nMetabolised in liver nExcreted mainly through urine nEnzyme inhibitor(p450) Clinical uses nSerious rickettsial infections nIn children whom tetracyclines are contraindicated nMeningitis nIn allergic patients to penicillin nTopically in bacterial eye infections except in chlamydial infections. Adverse effects nGastric upset (N.,V.,D.) nSuper infections nBone marrow depression nGray baby syndrome nHypersensitivity reactions nDrug interactions Aminoglycosides nBactericidal antibiotics nInhibits protein synthesis by binding to 30S ribosomal subunits. nActive against gram negative aerobic organisms. nPoorly absorbed orally nGiven parenterally (I.M,I.V.) nNot freely cross BBB Aminoglycosides nExcreted mainly unchanged in urine nMore active in alkaline medium nHave common adverse effects : nOtotoxicity nNephrotoxicity nNeuromuscular blocking effect nCNS (not common ). Clinical uses nStreptomycin nT.B. in combination with other antituberculous drugs. nEnterococcal endocarditis with penicillin. nSevere brucellosis with tetracycline Gentamicin nSevere infections caused by gram negative organisms as sepsis ,urinary tract infections & pneumonia caused by pseudomonas. nTopically for the treatment of infected burns,wounds,skin lesions,ocular, ear infections. Tobramycin nMore active against pseudomonas than gentamicin. nIneffective against mycobacteria nLess nephrotoxic and ototoxic than gentamicin. nUsed in treatment of bacteremia, osteomyelitis and pneumonia. Amikacin nHas the broadest spectrum nUsed for serious nosocomial infections by gram negative organisms. nIn T.B. as alternative to streptomycin nAtypical mycobacterial infections Neomycin nHighly nephrotoxic ,used only orally for gut sterilization before surgery or topically in skin infections,burn or eye infections. Contraindications of aminoglycosides nRenal dysfunction nPregnancy nDiminished hearing nMyasthenia gravis nRespiratory problems Precautions with: nLoop diuretics nCephalosporins nMonitor plasma level is useful. nNeostigmine reverses respiratory depression. FLUOROQUINOLONES (Ciprofloxacin,ofloxacin,norfloxaci nMechanism of action: nBlock bacterial DNA synthesis by inhibiting bacterial topoisomerase11(DNA gyrase ) and topoisomerase 1V. nAntibacterial activity : nHighly active against gram-negative aerobic bacteria. nActive against gram-positive bacteria. nMycoplasma,chlamydia,legionella,mycobacteria. Pharmacokinetics nWell absorbed orally. nWidely distributed in body fluids & tissues. nHalf-life(3-10h). nAbsorption is impaired by antacids. nConcentrated mainly in prostate,kidney,neutrophils ,macrophages. nExcreted through kidney. Clinical uses nU.T.I.caused by multidrug resistance organisms as pseudomonas. nBacterial diarrhea. nSoft tissues,bones,joints,intra-abdominal, respiratory infections caused by multidrug resistance organisms. nGonococcal infections. nLegionellosis. nChlamydial urethritis or cervicitis nT.B & atypical T.B. Adverse effects nN.V.D. nHeadache,dizziness,insomnia nSkin rash ,abnormal liver enzymes. nQT prolongation nDamage growing cartilage causing arthropathy. nTendinitis in adults Drug interactions & contraindications nWith antacids nElevate serum levels of theophyline increase the risk of seizure. nContraindicated in children ,adolescents ,pregnancy ,lactation ,epileptic patients. Miscellaneous Antibiotics nPolymyxins nActive against gram-negative including pseudomonas. nPolymyxin B is only available. nBactericidal inhibits cell wall synthesis. nUsed only topically . nHighly nephrotoxic. n Spectinomycin nBactericidal,inhibits protein synthesis by binding to 30S ribosomal subunits. nGiven I.M.I.as a single dose in treatment of gonorrhea. nPain at the site of injection. nExcreted through kidney . nNephrotoxicity is rare. Clindamycin nActive against gram-positive and anaerobic bacteria. nInhibits protein synthesis by binding to 50S ribosomal subunits. nGiven orally or parenterally nWidely distributed nCross placenta not BBB. nMetabolised in liver giving active metabolites. Excreted in bile & 10% in urine. nClinical uses: nAnaerobic infections minly in bones and joints . nConjunctivitis. nIn combination with aminoglycosides or cephalosporin is used to treat penetrating wounds of the abdomen & the gut. nFemale genital tract e.g. septic abortion ,pelvis abscess. nInstead of erythromycin for prophylaxis of endocarditis. nAdverse effects : nDiarrhea,Pseudomembranous colitis,hepatotoxicity,bone marrow suppression. Other inhibitors to cell wall synthesis nVancomycin nBactericidal nActive only on gram +ve bacteria. nPoorly absorbed orally nGiven by I.v.I nNot freely cross BBB nExcreted mainly through kidney Clinical uses nEndocarditis mainly caused by methicillin resistant staphylococci. nAlternative to penicillin in enterococcal endocarditis( in combination with gentamicin). nMeningitis( in combination with ceftriaxone or rifampin in highly resistant pneumococcus strains). nOrally in antibiotic associated enterocolitis Adverse effects nIrritation at the site of injection nOtotoxicity & nephrotoxicity . nRed man or red neck syndrome. nGastric upset. Bacitracin nBactericidal nNo cross resistance between it and other antimicrobial drugs. nActive against gram +ve organisms nUsed only topically in skin ,eye ,nose infections . nHighly nephrotoxic producing proteninuria, hematuria nHypersensitivity reactions nAs ointment in combination with polymyxin or neomycin for mixed bacterial infections. nAs