Isoniazid Causes Peripheral Neuritis
The correct answer is A) Peripheral neuritis. Isoniazid is the first-line antitubercular drug activated by the catalase-peroxidase enzyme (KatG) inside mycobacteria, and its most characteristic adverse effect is peripheral neuropathy (neuritis) 1, 2.
Mechanism of Activation
Isoniazid is a prodrug that requires activation by the mycobacterial catalase-peroxidase enzyme KatG before it can exert its bactericidal effects 3, 4. This activation step is essential for the drug's therapeutic action, and mutations in the katG gene are the primary mechanism of isoniazid resistance 3.
Peripheral Neuritis as the Characteristic Side Effect
Peripheral neuropathy is a well-established adverse effect of isoniazid, manifesting as numbness and paresthesias in the extremities, progressive loss of distal sensation, motor ataxia and weakness, and loss of deep tendon reflexes 2.
The mechanism involves pyridoxine (vitamin B6) depletion, as isoniazid interferes with pyridoxine metabolism 2.
Prevention is straightforward: pyridoxine supplementation at 10 mg/day prevents isoniazid-induced neuropathy 1. If neuropathy develops, the drug should be stopped promptly 1.
High-risk patients require prophylactic pyridoxine, including those with diabetes, uremia, alcoholism, malnutrition, and HIV infection 2.
Why the Other Options Are Incorrect
Optic neuritis (Option B) is the characteristic adverse effect of ethambutol, not isoniazid 1. This is a dose-related toxicity that requires monitoring of visual acuity.
Hyperuricemia (Option C) is caused by pyrazinamide, which can lead to arthralgia or arthritis 1.
Flu-like illness (Option D) is associated with rifampicin, particularly with intermittent dosing regimens, and can include fever, chills, and headache 1.
Clinical Monitoring Considerations
Monthly clinical evaluations are recommended for patients on isoniazid to assess for adverse effects 1.
Patients should be educated to immediately report persistent paresthesias of the hands and feet, as this indicates peripheral neuropathy requiring drug discontinuation 5.
While hepatotoxicity is the most serious adverse effect of isoniazid (occurring in 0.5-1% of patients, increasing with age) 1, 5, peripheral neuritis is the most characteristic neurological side effect directly related to the drug's mechanism and is preventable with pyridoxine supplementation 2.