Disulfiram

Sulfiram

Sulfiram is similar in structure to disulfiram, but has one less sulfur atom in its central chain. It is a much weaker inhibitor of aldehyde dehydrogenase than disulfiram and is used in the topical treatment of scabies.

General adverse effects and adverse reactions

Several adverse effects of disulfiram itself (as opposed to the aldehyde that it allows to accumulate) have been described. They include neurological reactions and skin reactions, but hepatotoxicity is the only previously reported life-threatening reaction, and it is rare [ ].

Disulfiram modifies the metabolism of many drugs by inhibiting the cytochrome CYP2E1. Adverse reactions to disulfiram occur with a frequency of 1 in 200 to 1 in 2000 per treatment-year [ ]. The death rate is about one per 25 000 patients per year, and hepatic failure accounts for most of these [ ]. Allergic reactions can occur. Tumor-inducing effects have not been described.

Cardiovascular

Disulfiram in a dose of 250–300 mg/day does not affect pulse rate, blood pressure, or plasma noradrenaline concentrations, but 500 mg/day causes an increase in plasma noradrenaline, increased systolic blood pressure both recumbent and erect, and an increased erect pulse rate. The raised blood pressure does not reach hypertensive values, but the results suggest increased sympathetic nervous system activity in patients who take disulfiram. Caution should therefore be exercised in using disulfiram in hypertensive patients. Close monitoring of blood pressure is advised, and the dose of disulfiram should preferably be reduced to 250 mg/day [ ].

Cardiac dysrhythmias occurred during a disulfiram + alcohol test in a 48-year-old man who had been an alcoholic for 5 years [ ]. After drinking a test amount of alcohol, he developed flushing, nausea, vomiting, sweating, dyspnea, and hyperventilation, palpitation, tremor, confusion, and syncope. The electrocardiogram showed atrial fibrillation and non-sustained bouts of ventricular tachycardia of 7–8/minute. He also had severe hypotension.

A 27-year-old man took disulfiram and ethanol and developed significant hypotension and ischemic electrocardiographic changes [ ]. He was treated with intravenous fluids and noradrenaline, which has been advocated as the pressor agent of choice.

Nervous system

Disulfiram can cause a polyneuritis [ ], which can occasionally be fulminant and irreversible.

• A 39-year-old woman developed a severe sensorimotor polyneuritis after taking ethanol and disulfiram in high doses [ ]. The disorder was similar to other cases of disulfiram neuropathy, but was acute and more severe.

The neurotoxic effects of disulfiram have been compared with those of carbon disulfide, a disulfiram metabolite [ ]. The results suggested that carbon disulfide may be responsible for the behavioral and neurological adverse effects of disulfiram. If so, other toxic effects of carbon disulfide might follow administration of high doses of disulfiram, such as parkinsonism, psychotic behavior, and encephalopathy.

Disulfiram-induced neurotoxicity caused parkinsonism in a man who had been an alcoholic for 10 years [ ].

• A 52-year-old alcoholic stopped drinking in August 1996 and started to take disulfiram 500 mg/day. His usual medications had been aspirin 300 mg/day and levothyroxine 100 micrograms/day. He had had severe loss of visual acuity (2/10) in the left eye 3 months before admission. He was admitted to hospital because of drowsiness. Neurological examination showed severe hypophonia, difficulty in swallowing, and mild rigidity of the limbs. Disulfiram was withdrawn but the other medications were maintained. His drowsiness improved over 5 days, but he remained bradykinetic, with extra-pyramidal hypertonia, facial hypomobility, and abnormal posture. His gait was slow and shuffling.

• A 20-year-old woman was referred for implantation of an intrathecal baclofen pump [ ]. She had had severe dystonia and spasticity following a suicide attempt with disulfiram at age 14 years. T ₁ -weighted MRI scanning of her brain showed bilateral globus pallidus infarction. She had profound relief of spasticity after intrathecal test injections of baclofen and underwent implantation of an intrathecal baclofen pump. Her spasticity subsequently improved.

Sensory systems

Retrobulbar neuritis can be part of a disulfiram-induced polyneuritis, with dramatic reduction in visual acuity and impaired color perception [ ]. This complication is rare but serious. It occurs at dosages of 500 mg/day, and there is a latent period of 2–36 months. Tobacco abuse is thought to be a predisposing factor. Disulfiram can cause optic neuropathy [ , ].