ISONIAZIDE ANTITUBERCULAR DRUG

DESCRIPTION

PHARMACOLOGY-

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 to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.

MECHANISM OF ACTION-

Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.

SIDE EFFECTS-

Gastrointestinal reactions include nausea and vomiting. Aplastic anemia, thrombocytopenia, and agranulocytosis due to lack of production of red blood cells, platelets, and white blood cells by the bone marrow, respectively can also occur.Hypersensitivity reactions are also common and can present with a maculopapular rash and fever.Headache, poor concentration, weight gain, poor memory, insomnia, and depression have all been associated with isoniazid use.All patients and healthcare workers should be aware of these serious side effects, especially if suicidal ideation or behavior are suspecteD.

DRUG-DRUG INTERACTION-

1.The risk or severity of adverse effects can be increased when Isoniazid is combined with Acetaminophen.

2.The metabolism of Acetylcholine can be decreased when combined with Isoniazid.

3.The metabolism of Adinazolam can be decreased when combined with Isoniazid.

4.The metabolism of Ajmaline can be decreased when combined with Isoniazid.

5.The serum concentration of Isoniazid can be decreased when it is combined with Alclometasone.

6.The serum concentration of Isoniazid can be decreased when it is combined with Aldosterone.

7. The metabolism of Almotriptan can be decreased when combined with Isoniazid.

USES-

1. Isoniazid is approved for latent and active tuberculous infections. For the latter, it must be used in combination with other tuberculosis medications to prevent the development of drug resistance.

2. Isoniazid has been approved as prophylactic therapy for the following populations:

3.People with HIV infection and a PPD reaction of at least 5 mm induration

4.Contacts of people with tuberculosis and who have a PPD reaction at least 5 mm induration

5.People whose PPD reactions convert from negative to positive in a two-year period – at least 10   mm induration for those up to 35 years of age, and at least 15 mm induration for those at least 35   years old

6.People with pulmonary damage on their chest X-ray that is likely to be due to healed tuberculosis and also have a PPD reaction at least 5 mm induration

7.Injection drug users whose HIV status is negative who have a PPD reaction at least 10 mm induration

8.People with a PPD of greater than or equal to 10 mm induration who are foreign-born from high   prevalence geographical regions, low-income populations, and patients residing in long-term     facilities

REFERENCE- Tripathi K.D. "Essentials of Medical Pharmacology", 7th Edition, page no- 766