ATT Drug that kills slowly or intermittently dividing bacteria:

Ref: KDT 6th ed. pg. 740-44, Katzung Pharma 14th ed. pg. 845RIFAMPICIN* It is a tuberculocidal agent of M. tuberculosis in addition to staph, aureus, pseudomonas, proteus, legionella etc.* It has bactericidal action of which covers all subpopulations of TB bacilli, bat acts best on slowely or intermittently dividing ones as well as on many atypical mycobacteria.* Both intracellular and extracellular bacilli are affected.* MOA: It inhibits DNA dependent RNA synthesis* Resistance of rifampicin is due to rpoB gene.* Adverse effects:# Hepatoxicity: MC/Major side effect# Rifampicin imparts a harmless orange color to urine, sweat, tears, and contact lenses (soft lenses may be permanently stained).# Occasional adverse effects include rashes, thrombocytopenia, and nephritis.# It may cause cholestatic jaundice and occasionally hepatitis and flu-like symptoms.ISONIAZID* It is primarily tuberculocidal. Fast multiplying organisms are rapidly killed but quiescent ones are only inhibited.* Acts on intracellular as well as extracellular TB bacilli and is equally active in acidic and alkaline medium.* MOA: Inhibit synthesis of mycolic acid, which is a unique fatty acid component of mycobacterial cell wall.* If given alone, resistance occurs in about 2-3 months* Most common mechanism of INH resistance: Mutation of catalase-peroxidase gene > Mutation of inh-A gene.* Adverse effects:# Isoniazid-induced hepatitis is the most common major toxic effect# Peripheral neuropathy is observed in 10-20% of patients# Neuropathy is due to a relative pyridoxine (Vit B6) deficiency. Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine.# Central nervous system toxicity, which is less common, includes memory loss, psychosis, and seizures.PYRAZINAMIDE* It is weakly tuberculocidal. PYZ is more lethal to intracellularly located bacilli and to those at sites showing an inflammatory response.* MOA: Resembles that of INH. It inhibits mycolic acid synthesis but by interacting with a different fatty acid synthase encoding gene.* Resistance of PYZ due to mutation in pncA gene.* Adverse effects: Hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemiaETHAMBUTOL* Selectively tubecolostatic agent and clinically as active as streptomycin. Fast multiplying bacilli are more susceptible as are many atypical mycobacteria.* MOA: Poorly understood, but it has been found to inhibit arabinosyl transferases involved in arabinogalactan synthesis and to interfere with mycolic acid incorporation in mycobacterial cell wall.* Resistance of ethambutol due to alteration in the drug target gene- emb gene.* Adverse effects: Retrobulbar neuritis, resulting in loss of visual acuity and red-green color blindness.STREPTOMYCIN* Tuberculocidal agent, acts only on extracellular bacilli. It penetrates the tubercular cavities but doesn't crosses the CSF. Has poor action on acidic medium.* Adverse effects: Ototoxic and nephrotoxic.* Resistance is due to a point mutation in either the rpsL gene or rrs gene.