A PRESENTAION ON
Complex macrocyclic antibiotics.
Naturally produce by Streptomyces mediterranei.
Bactericidal drug (intracellular and extracellular).
Particulary effective against Mycobacteria.
Used to treat TB, Leprosy and mycobacterium avium
Based on production
a) Natural rifamycins
e.g. rifamycins B,O,SV and x.
b) Semi-synthetic rifamycins derivatives
e.g. rifampicin, rifabutin, rifaximin and
MECHANISM OF ACTION
• Inhibits bacterial DNA-dependent RNA
synthesis by inhibiting bacterial DNA-
dependent RNA polymerase.
• Halts initiation of mRNA transcription
• Prevention of translation of polypeptides
• Inhibits only prokaryotic DNA-primed RNA
• In normal concentration-does not inhibit
• High activity against gram +ve and
• Suceptible organisms:
Stayphylococcus, Nesseria, Chlamydia,
Mycobacterium sps etc.
• Some activity against a few gram –ve;
Brucella and vaccinia virus
• Natural resistance in gram –ve(due to failure
to penetrate organism)
• Resistance quickly when use sole.
• Alteration in DNA dependent RNA
• Well absorbed (40-70%) from GI tract in oral
• I/m injection site – rapid absorption.
• Rapidly distributed to body tissues & fluids.
• Enters into the cell.
• Effective concentration reaches to many
organs and body fluid including CSF.
• Also penetrate abscess and caseous material.
• In liver by deacetylated.
• Mainly in bile(60-65%) and to a lesser extent
• GI disturbances-
abdominal cramps with or without diarrhoea
• CNS effects-
ataxia, and confusion
• Patient with Hypersensitivity to rifamycins.
• Cautiously use in patient with pre-existing
• Use carefully in pregnant animal, although
significant teratogenicity has not been
Help in the metabolism/elimination of DRUGS
• digitalis, coticosteriods,
• quinidine, barbiturates,
• ketoconazole, propranolol,
• verapamil and oral anticoagulant
(Effective liver enzyme inducer-hepatic cytochrome P450)
• Synergism with amphotericin B
• Drugs Increasing toxicity of rifamycins
azoles protease inhibitors
The macrolide Clarithromycin
Nonnucleoside reverse transcriptase inhibitors
(increase levels of rifamycins by inhibiting CYP450 enzymes )