Increased sympathetic nervous system activity in alcoholic patients treated with disulfiram

Abstract

The authors measured plasma levels of norepinephrine (NE) and dopamine beta-hydroxylase (DBH), pulse rates, and blood pressures of 81 hospitalized alcoholic patients. Treatment with 500 mg/day of disulfiram (but not 250 mg/day or placebo) resulted in small but significant increases in plasma NE and in blood pressure. The 500-mg dose did not appreciably inhibit DBH. Patients receiving high doses of disulfiram should have their blood pressure monitored and their dose decreased to 250 mg/day when possible.

Disulfiram-Induced Reversible Hypertension: A Prospective Case Series and Review of The Literature

“…Peripheral synthesis of NE is probably not affected by the DSF as it is noted to have no effect on the pressor effect of tyramine and NE,[ 7 ] as also plasma levels of NE increase following long-term high-dose (> 500 mg/day) DSF therapy. [ 5 ] DSF limits NE synthesis in sympathetic nerves but not in the adrenal medulla, possibly due to large reserve of DBH in adrenals rendering DSF incapable of making DBH activity rate limiting and also due to limited access of drug to the adrenal DBH. [ 7 ] As DBH enzyme doesn’t cross the blood brain barrier and DSF does not inhibit plasma DBH levels, there remains possibility of central inhibition of DBH in brain and possibly deplete brain NE levels, thereby increase in BP.…”

“…[ 1 ] Its toxicity may present different clinical aspects, though the mechanism (direct or idiosyncratic) remains unclear. [ 2 ] DSF (125-500 mg/day)-related hypertension (HTN) has been documented in very few earlier reports to cause reversible, dose-dependent grade 1-2 HTN within 2-3 weeks of administration,[ 3 4 5 6 7 ] while a systematic review observed no change in blood pressure (BP) with 6 weeks of DSF (250 mg/day) therapy. [ 8 ] Surprisingly, most of the related articles were during the period between 1950s and 1980s.…”

Disulfiram Induced Reversible Hypertension: A Prospective Case Study and Brief Review

“…Peripheral synthesis of NE is probably not affected by the DSF as it is noted to have no effect on the pressor effect of tyramine and NE,[6] as also plasma levels of NE increase following long-term high-dose (>500 mg/ day) DSF therapy. [4] However, DSF increases the nitro-glycerine induced postural hypotension while decreasing the accompanying tachycardia. [6] This implies that DSF impairs the BP regulation through central nervous system by inhibition of the central DBH activity resulting in decreased central NE synthesis, which may interfere with the central alpha-adrenergic activity at the bulbar sympathetic cardio-accelerator, and vasomotor centers, resulting in increased BP,[3] opposite of which is noted with antihypertensive agents like central alpha agonists (clonidine, methyldopa, reserpine, and guanfacine).…”

“…[1] DSF toxicity may present the different clinical aspects, though the mechanism of toxicity (direct or idiosyncratic) remains unclear. [2] DSF (125-500 mg/ day) related hypertension has been documented in very few earlier reports to cause reversible, dose-dependent stage-I and stage-II hypertension within 2-3 weeks of administration,[3456] while a systematic review observed no change in blood pressure (BP) with 6 weeks of DSF (250 mg/day) therapy. [7] Surprisingly, most of the related articles were during the period between 1950s and 1980s.…”

Pharmacoprophylaxis of alcohol dependence: Review and update Part I: Pharmacology

“…[1112] The result with therapeutic dose to man vary. [1314] Patients with very low activity of dopamine hydroxylase appear to be sensitive to disulfiram in the sense that they may develop a transient psychotic condition, probably because of an increased ratio between dopamine and noradrenaline in the brain. [13]…”