Friday, April 15, 2011


It is also referred to as INH as its full name is “Isonicotinic acid hydrazide”.
Mechanism of action:
It causes a decreased synthesis of mycolic acid. Mycolic acid is a constituent of mycobacterial cell wall that is thought to be responsible for the acid fastness of the bacteria.

KatG is mycobacterial catalase (peroxidase),

AcpM is Acyl carrier protein,

KaSA is Beta ketoacyl carrier protein synthetase.

Here in the above diagram, mycolic acid synthesis is blocked as mycolic acid is produced by the incorporation of cyclopropane ring near the centre of acyl chain.

It is readily absorbed by GIT. 300 mg of oral dose achieves peak plasma concentration of 3-5μg/ml in 1-2 hours. The drug diffuses easily into bodily fluids and cells.

It is metabolized by liver N-acetyltransferase (in which its acetylation occurs).

Average half life in peoples with rapid acetylation is 1 hour and in peoples with slow acetylation it is 3 hours.

Elimination is done via urine.

Therapeutic uses:
It is used in the prophylaxis as well as treatment of tuberculosis.

The usual adult dose is 5mg/kg/day to a maximum of 300 mg/day.

Adverse effects:
It may cause fever, skin rashes, Insomnia and restlessness. It may also induce hepatitis characterized by loss of appetite, nausea and vomiting. Hepatitis is thought to be associated to the metabolite monoacetylhydrazine.

Sometimes peripheral neuropathy (neuropathy is caused by pyridoxine deficiency and isoniazid causes an increased pyridoxine excretion) is also observed.

Resistance is found to be due to chromosomal alterations resulting in change in genetic material of KatG or due to over expression of enoyl acyl carrier protein reductase.
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