ISONIAZID (Isonicotinic acid hydrazid; INH)
Pharmacokinetics:
Isoniazid is well absorbed from GIT. It diffuses readily into all tissues, body fluids, (CSF, Pleural fluids etc… )
Isoniazid is metabolized in the liver by acetylation which depends on genetic factors that determine whether a person is a slow or rapid acetylator of the drug , with slow acetylators patients enjoying a better therapeutic response. Rapid acetylators are more likely to develop hepatotoxicity, while the slow acetylators are liable to neuropathy.
The half-life in slow inactivators is 3 hours and in rapid inactivators, 1 hour. Isoniazid is excreted in the urine partly as unchanged drug and partly in the acetylated or otherwise inactivated form.
N.B. **INH causes pyridoxine deficiency which lead to neurotoxicity**. #Z
Antimycobacterial activity:Z
Isoniazid is a selective antituberculous drug and has no activity against other bacteria. Isoniazid is bactericidal for TB organisms and is able to act on intracellular and extracellular bacilli
Mechanism of action:
- inhibits synthesis of mycolic acid, which is important constituent of cell wall.
- inhibits the desaturase enzyme, which is essential for cell wall synthesis of bacilli. Other bacteria do not contain mycolic acid & so is not sensitive to INH.
- may interfere with NAD and form false NAD. This will disrupt carbohydrate and fat metabolism of the bacilli
Therapeutic uses:
Isoniazid is the keystone of antituberculous drugs since it is the most active, relatively lack of toxicity and low cost. Also, it achieves a high level in all body cells and fluids.
Isoniazid is used alone as chemoprophylaxis in the following cases:Z
- Very close contact to recent diagnosed cases.
- Persons converting from negative to positive tuberculin skin test. - (in immunosuppressant patients)
Adverse effects:
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Neurotoxicity in the form of: peripheral neuropathy (numbness, tingling of lower limbs) Optic neuritis. C.N.S toxicity as memory impairment, dizziness, convulsion. Neurotoxcity is more common in slow acetylators and it is due to pyridoxine deficiency. It can be prevented by vitamin B6.
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Hepatocellular toxicity: This risk increases with age, presence of liver disease and in rapid acetylators. So, follow up the patients by liver function tests especially in the people of high risk.
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Hypersensitivity reactions: Skin rashes, fever .
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GIT upset, anaemia and systemic lupus.
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Haemolytic anaemia in individuals with G6-PD deficiency