Peripheral neuritis due to hydrazide derivatives.

The antituberculous activity of isoniazid used alone or in combination with streptomycin or para-aminosalicylic acid (PAS) has been established.’ One of the most favorable properties of isoniazid is the low incidence of significant toxicity resulting from its use when doses of 3 to 5 mg. per kilogram per day are administered. Some of the reactions reported include toxic psychosis, convulsions, dizziness, euphoria, increased sensitivity to sympathomimetic drugs, hyperreflexia, weakness of the legs, headache, ataxia, muscle tremors, tinnitus, disturbed vision, insomnia, drowsiness, urinary incontinence, polyuria, delay in initiation of micturition, constipation, dryness of the mouth, drug fever, variations in sexual activity, pruritis, skin rash, nausea, vomiting, exertional dyspnea and transitory edema.2 Although this is a long list, toxic reactions are infrequent. The need for discontinuing the drug because of serious toxic reactions occurs in approximately 1 per cent of cases.3 It is interesting to note the dominance of toxic effects referrable to the nervous system. In our studies with isoniazid, as well as other hydrazides, we have used various dosage schedules in an attempt to evaluate therapeutic efficacy, roentgenographic response, incidence of sputum conversion, development of bacterial resistance and drug toxicity. In the course of these studies we have observed 19 patients who have developed peripheral neuritis of varying degrees of severity. Isoniazid was administered to 15. Three received 200 mg. daily; and 11 received 400 mg. daily. These doses represent 2.5 mg. to 10 mg. per kilogram per day. Eleven of the 15 received more than 5 mg. per kilogram per day. This indicates a correlation between the size of the dose and the development of neuritis.