Isoniazid ( isonicotinic acid hydrazide ,INH , is a pro- drug that requires mycobacterium tuberculosis catalase peroxidase enzyme to be active against mycobacterium and does not have any effect on mycobacteria before this enzyme activation. It is one of the most commonly used drugs in the treatment of tuberculosis, because mycobacterium tuberculosis show high sensitivity to it. However it should be noted that this drug is effective against growing basil and cannot eradicate the latent basil. Furthermore, its activity against mycobacterium is carried out under completely aerobic conditions and under anaerobic conditions does not have an inhibitory effect on mycobacterium tuberculosis. The main reason for this event is the need of oxygen for …show more content…
The mechanism of action is as follows: Initially, given that it is a pro drug, it should be activated by the mycobacterium catalase peroxidase enzyme, which is regulated by the kat G gene. Then it enters tuberculosis bacilli by active diffusion. After activation by kat G, isoniazid converted to a wide range of radicals or reactive species and isotonic acids which can include both inactive oxygen species and radical species organic radicals. These radicals and species role is to attack multiple targets include: mycolic acid Synthesis, damage to DNA, lipid peroxidation and the nicotinamide adenine dinucleotide (NAD) metabolism in the cell. It is also responsible for the bactericidal activity of isoniazid. Isoniazid has inhibitory effect on mycolic acid synthesis and seems to be its main purpose. Evidence suggests that after treatment with isoniazid, there is a lack of fatty acids on mycobacterium cell wall. Also inh A enzyme acts as molecular target for isoniazid inhibition. This enzyme plays a role in prolongation of the fatty acids that contribute to mycolic acid synthesis. Another effect mentioned was interference on the NAD metabolism by being incorporated into NAD and forming pseudo NAD which can 't be as an electron acceptor in respiratory chain. Thus affected various functions of NAD such as, energy metabolism and DNA repairing. DNA ligase play an important role in DNA repairing which needs NAD as co-factor .when its function interrupted by isoniazid it can 't play its role as co factor and as a result Mycobacterium DNA repair will is not done properly. Despite the above mentioned mechanisms, the effect of isoniazid on tuberculosis basil is much higher and the determination of the order of these mechanisms is not feasible and requires further