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CHEMOTHERAPY. ANTIBIOTICS Chemical substances produced by microorganisms and have the capacity to inhibit or destroy other organisms . CHEMOTHERAPEUTIC AGENT Synthetic chemical substances used to inhibit or destroy microorganisms. CLASSIFICATION OF ANTIBIOTICS ACCORDING TO MECHANISM OF ACTION.
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CHEMOTHERAPY • ANTIBIOTICSChemical substances produced by microorganisms and havethe capacitytoinhibit or destroy other organisms . • CHEMOTHERAPEUTIC AGENT • Synthetic chemical substances used toinhibit or destroy microorganisms.
CLASSIFICATION OF ANTIBIOTICSACCORDING TO MECHANISM OF ACTION • !INHIBITION OF CELL WALLSYNTHESIS. • INHIBITION OFPROTEIN SYNTHESIS . • INHIBITION OF NUCLEIC ACIDSYNTHESIS . • INHIBITION OF CELL MEMBRANEFUNCTIONS .
According to spectrum • 1- Narrow spectrum as penicillins ,aminoglycosides • 2- Broad spectrum as tetracyclines , chloramphenicol
REASONS FOR FAILUREOF CHEMOTHERAPY . • 1-WRONG DIAGNOSIS2-WRONG CHOICE Of DRUG3-WRONG DOSE4-DEVELOPMENT OF RESISTANCE5-INFECTIONS WITHMORE THANONE ORGANISM6-PRESENCE OF PUS ,BLOOD ,NECROTIC TISSUES .
Host factors in selection of antimicrobial therapy • 1-Allergy or history of adverse reactions. • 2-Age of patient • 3-Pregnancy • 4-Genetic or metabolic abnormalities5-Renal & hepatic functions6-Site of infections7-Concomitant drug therapy • 8-Underlying disease state(s)
Failure of Antimicrobial therapy • 1-Failure caused by drug selection: • Inappropriate drug selection or dosage or route of administration . For example: • Selection of a bacteriostatic drug for endocarditis. • administration of a drug by I.M. to a patient with a weak peripheral circulation ( shock). May result inadequate therapy. • Malabsorption of a drug product because of GIT disease or a drug interaction ( combination of tetracyclines with milk products ). • Accelerated drug elimination as in patient with cystic fibrosis or during pregnancy may result in rapid clearance or large volume of distribution resulting in low serum concentrations as with aminoglycosides. • Inactivation of antimicrobial agents by another drug. • Poor penetration into the site of infection ( c.n.s., eye, prostate).
Failure caused by microorganisms(BACTERIAL RESISTANCE ) • 1-Inactivation of antibiotics by enzymes. • 2- Modification of target by mutation. 3-Impaired penetration of drug to target ,occurs only in gram-negative species. 4-The presence of an efflux pumpproduced by gram-negative organisms which consists of cytoplasmic and periplasmic protein components that transport antibiotics from the periplasm back across the outer membrane.
ANTIMICROBIAL COMBINATION • SYNERGISM!-SEQUENTIAL SYNERGISM2-INHIBITIONOF ENZYMATICACTIVITY • 3-ENHANCEMENT OFANTIMICROBIALUP TAKE • ANTAGONISM
Aim of chemotherapeutic combination • 1-Broaden the spectrum of antibacterial activity e.g: clindamycin+ gentamycin • 2- Reduce the doses • 3- Reduce the side effects • 4- Overcome drug resistance(delay the rate of drug resistance) as in treatment of TB or pseudomonal infections. • 5- Produce a more potent compound • (produce a synergistic effect) as in co-trimoxazole combination or as in penicillin with gentamycin in treatment of bacterial endocarditis. • 6-Treatment of severe infections of unknownetiology as in septicaemia.
Drug interactions with antibiotics • 1- Aminoglycosides • A- Increase the effects of curare • B- Increase the nephrotoxicity & ototoxicity of loop diuretics • 2- Enzyme inhibitors as chloramphenicol & erythromycin increase the action & toxicity of other drugs as digitalis • 3- Enzyme inducers as rifampicin decrease the action of other drugs as oral anticoagulants or oral contraceptives.
Drug interactions • 4- Sulphamethoxazole + trimethoprim result in bactericidal effect. • Sulphonamides displace oral hypoglycemic from their plasma protein binding causing hypoglycemia