What is the active metabolite of isoniazid?

Acetylhydrazine (AcHz), hydrazine (Hz), and acetylisoniazid (AcINH) are the major metabolites of INH. Studies of INH hepatotoxicity in rats showed that AcINH and AcHz can cause hepatic necrosis; however, treatment with INH directly even at high dose and long term did not cause toxicity9, 15.

Can isoniazid cause hepatitis?

Most cases of INH hepatotoxicity are mild and commonly resolve despite continued therapy with INH; however, a small number of adult patients taking INH develop severe hepatitis that may progress to liver failure and death if the drug is not stopped promptly.

What is an Acetylator?

: an organism that acetylates a substance during metabolism —used especially to describe the rate at which a person acetylates certain drugs (such as isoniazid, hydralazine, or sulfamethazine) in the body People known as slow acetylators, for instance, take a longer time than fast acetylators to clear certain drugs …

What type of antibiotic is isoniazid?

Isoniazid is in a class of medications called antituberculosis agents. It works by killing the bacteria that cause tuberculosis.

Which is the best test for determining acetylator status?

Laboratories differ in the drugs used to assess acetylator status – consult pathologist before commencing test. If the protocol specifies caffeine or a drug which the patient is already taking, a random specimen of urine is satisfactory.

What kind of drug is a slow acetylator?

Such drugs include sulphonamides (especially salicylazosulphapyridine), hydralazine, procainamide, isoniazid. Slow acetylators are more likely to develop toxicity when given the drug. Pillans PI. Intern Med J 2001; 31: 476-478.

Why are slow acetylators more susceptible to bladder cancer?

Thus in the case of carcinogenic aromatic amines such as benzidine, it has been suggested that slow acetylators are more susceptible to bladder cancer. (Thus one study showed a relative risk of slow: rapid of 1.36 and for individuals exposed to aromatic amines in industry a relative risk of slow: rapid of 1.7.)

What is the role of acetylation in carcinogenicity?

Studies have shown that rapid acetylator mice have greater DNA adduct formation with 2-aminofluorene than slow acetylator mice. The role of acetylation in carcinogenicity is discussed in more detail in Chapter 7 with regard to aminofluorene derivatives.