Isoniazid

Absorption

Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.

Toxicity

LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.

Description

Isoniazid, the hydrazide of isonicotinic acid was introduced into medical practice for treating tuberculosis in 1953. Isoniazid exhibits bactericidal action on Mycobacterium tuberculosis. It inhibits the synthesis of mycolic acid, an important component of the cell membrane of mycobacteria. Mycolic acid is specific only to mycobacteria, and it is the cause of the selective toxicity of the drug with respect to these microorganisms.
Mutants that are resistant to isoniazid are rarely seen in nature, and in a spontaneously growing population of tuberculous bacillus there is approximately one mutant in every 105 –106 organisms. Large populations of microorganisms of the order 109 –1010 bacilli in the pulmonary cavities contain a significant number of resistant mutants. If only isoniazid is taken during treatment, an increased number of mutants will be observed and they will eventually become the dominant phenotype. The transformation from sensitive to nonsensitive microorganisms during treatment is called secondary or acquired resistance, which can originate over the course of a few weeks. Isoniazid is the most important drug for treating pulmonary and nonpulmonary forms of tuberculosis. It is active against both intracellular and extracellular organisms. In order to prevent secondary resistance, isoniazid should be used with other effective drugs (usually rifampin). Synonyms of this drug are tubazid, andrazide, niazid, piridizin, and many others.

Description

Isoniazid is a first-line antibiotic used in the prevention and treatment of tuberculosis. It is currently the subject of various clinical trials for use in preventing TB in HIV-infected patients, who have a high risk of contracting the infection.

The Uses of Isoniazid

Isoniazid is an antimicrobial used for the prevention of tuberculosis infection or used concurrently with another agent for the treatment of tuberculosis infection. Rifampin, pyrazinamide, or both of these agents are commonly used with isoniazid. Isoniazid is the only Food and Drug Administration approved drug to treat latent tuberculosis in order to prevent it from becoming active.

Indications

Isoniazid is used for the treatment of all forms of tuberculosis in which organisms are susceptible. It is also used in combination with rifampin and pyrazinamide.

Background

Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.

What are the applications of Application

Isoniazid is an antituberculosis agent and an inhibitor/activator of CYP isoenzymes

Pharmacokinetics

Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly.

Metabolism

Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase.