Rifampin kills tubercle bacilli by
Rifampin (Rifampicin, R) Mech of action:- Rifampin interrupts RNA synthesis by binding to b subunit of mycobacterial DNA-dependent RNA polymerase (encoded by rpoB gene) and blocking its polymerizing function. Pharmacokinetics:- It is well absorbed orally, (bioavailability is ~ 70%), but food decreases absorption; rifampin is to be taken in empty stomach. It is widely distributed in the body: penetrates intracellularly, enters tubercular cavities, caseous masses and placenta. Though it crosses meninges, it is largely pumped out from CNS by P-glycoprotein. It is metabolized in liver to an active deacetylated metabolite which is excreted mainly in bile, some in urine also, t 1/2 of rifampin is variable (2-5 hours). Rifampin resistance:- It is nearly always due to mutation in the rpoB gene reducing its affinity for the drug. No cross resistance with any other antitubercular drug, except rifampin congeners, has been noted. uses of rifampin :- 1. Leprosy, Tuberculosis 2. Prophylaxis of Meningococcal and H. influenzae meningitis and carrier state. 3. Second/third choice drug for MRSA, diphtheroids and Legionella infections. 4. Combination of doxycycline and rifampin is the first line therapy of brucellosis. Ref:- kd tripathi; pg num:-768
Inhibiting mycobacterial DNA synthesis
Inhibiting synthesis of mycolic acids in mycobacteria
Binding to mycobacterial DNA dependent RNA polymerase
Damaging mycobacterial mitochondria
Antibiotics