Pharmacological and Parenteral Therapies Q 31

Correct Answer: D. Streptomycin

Streptomycin is an aminoglycoside and damage to the 8th cranial nerve (ototoxicity) is a common side effect of aminoglycosides. Ototoxicity and vestibular impairment are often thought to be the hallmark of streptomycin toxicity. In extreme cases, deafness may occur due to ototoxicity, thus caution must be exercised when combining streptomycin with other potentially ototoxic drugs. Vestibular impairment usually manifests during the course of treatment and is typically permanent.

Option A: Isoniazid may cause serious damage to the liver. Isoniazid is metabolized primarily by the liver, by acetylation of N-acetyltransferase 2 (NAT2). Three metabolites have implications that correlate with the liver injury associated with the drug: acetyl hydrazine (AcHz), hydrazine (Hz), and a metabolite from the bioactivation of isoniazid itself. There is considerable variation in acetylation rate and elimination half-life from individual to individual, which is not accounted for by dose and concentration, and this appears to contribute to risk for hepatotoxicity as well as the other adverse effects associated with isoniazid.

Option B: Despite having excellent efficacy against TB in both in vitro experiments and clinical trials, PAS was eventually replaced with better-tolerated ethambutol due to gastrointestinal disturbance associated with the usage of PAS.

Option C: One of the most well-known adverse effects is ototoxicity. The effect of ototoxicity is dose-related, with greater than 40% of adults developing toxicity at doses that were greater than 50 mg/kg and around 0 to 3% of adults developing toxicity at 15 mg/kg/daily. The manifestation of EMB-induced optic neuropathy appears to be from EMB’s chelation of copper. A study with 60 patients undergoing treatment with ethambutol monitored their serum copper levels.