Isoniazid may show cross-resistance with which of the following anti-tubercular drugs?
Isoniazid (H) may show cross-resistance with ethionamide due to mutation in inhA gene. Isoniazid: It is a prodrug activated by catalase-peroxidase (coded by KatG). Both inducer and inhibitor. Potent inhibitor of CYP2C19,CYP3A. Weak inhibitor of CYP2D6. Inducer of CYP2E1 It is effective against intra- as well as extra-cellular mycobacteria. Action is most marked against rapidly multiplying bacilli (less effective against slow multipliers). It is widely distributed in the body and has maximum CSF penetration. It is effective orally and metabolized by ACETYLATION which is genetically controlled. Fast acetylators require high dose and slow acetylators are predisposed to toxicity (paicularly peripheral neuritis). It is an essential component of multi-drug therapy of tuberculosis and is drug of choice (used solely) for prophylaxis of tuberculosis and for treatment of latent tuberculosis infection. Resistance occurs due to mutation in Kat G (gene for catalse-peroxidase) or inhA. Mutation in kat G is responsible for high level resistance. It causes peripheral neuritis that can be prevented and treated by pyridoxine. It is also hepatotoxic. Rash, fever, anemia, optic neuritis, seizures, lupus like syndrome, transient memory loss, psychosis and gynaecomastia has also been repoed with this drug.
Rifampicin
Cycloserine
Streptomycin
Ethionamide
Mycobacterial Diseases (TB, Leprosy and MAC)