Ans) d (Increased metabolism......) Ref KDT 6th ed p74l. KatzungRifampin inhibits DNA-dependent RNA polymerase of mycobacteria and other microorganisms by forming a stable drug-enzyme complex, leading to suppression of initiation of chain formation (but not chain elongation) in RNA synthesis. More specifically, the b subunit of this complex enzyme is the site of action of the drug, although rifampin binds only to the holoenzyme. Nuclear RNA polymerases from a variety of eukaryotic cells do not bind rifampin, and RNA synthesis is correspondingly unaffected in eukaryotic cells. High concentrations of rifamycin antibiotics can inhibit RNA synthesis in mammalian mitochondria, viral DNA-dependent RNA polymerases, and reverse transcriptases. Rifampin is bactericidal for both intracellular and extracellular microorganisms.A primary action of isoniazid is to inhibit the biosynthesis acids, branched lipids that are attached to a unique polysaccharide, arabino galactan, to form part of the mycobacterial cell wall.* Adjustment of dosageof rifampicin is not necessary in patients with impaired renal function.* It readily penetrates most tissues and into phagocytic cells. So they get concentrated mainly in lymphocytes and macrophages and not in neutrophils It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those that are sequestrated in abscesses and lung cavities.* Rifampicin, anticonvulsants including phenobarbitone, glucocorticoids induce CYP3 A soenzymes. Cyclosporine is metabolised in liver by CYP3A4 and excreted in bile. As rifampicin is an inducer of CYP3 A4, it lowers the blood levels of cyclosporine when given concomitantly