Enalapril effects on alcohol intake and other consummatory behaviors in alcoholics

Abstract

Animal studies suggest that angiotensin-converting enzyme inhibitors decrease alcohol intake. In a double-blind crossover study 42 normotensive alcoholics (36 men and six women) aged 24 to 65 years, consuming 8.2 +/- 2.3 (mean +/- SD) standard alcoholic drinks per day, were randomized to enalapril, 10 mg/day (n = 20) or 20 mg/day (n = 22), and placebo for 4 weeks. They monitored their daily alcohol intake and attended biweekly assessments, but no other treatment or advice was given. Compliance and alcohol intake were verified objectively. Mean daily alcoholic drinks were not significantly different during 10 mg/day enalapril (mean +/- SEM, 7.5 +/- 0.5), and its placebo (7.2 +/- 0.5), but both decreased from baseline (8.1 +/- 0.5; both p less than 0.05). Similarly, mean daily drinks during 20 mg/day enalapril (6.8 +/- 0.6) and its placebo (7.2 +/- 0.4) was not significantly different, but both were lower than baseline (8.3 +/- 0.5; both p less than 0.01). Fourteen (64%) of the patients taking 20 mg/day enalapril decreased alcohol intake from placebo by an average of 21% (range, 1.6% to 78.3%). Self-ratings of interest, desire, craving, and liking for alcohol also decreased from baseline during enalapril and placebo treatments, but the effects of both were similar. Plasma renin activity increased, compared with placebo, after 10 mg/day enalapril (from 0.3 +/- 0.2 [mean +/- SD] to 1.9 +/- 1.5 ng/L/sec) and after 20 mg/day enalapril (from 0.4 +/- 0.3 to 2.8 +/- 4.0 ng/L/sec) (both p less than 0.05). Blood pressure decreased within a normotensive range, compared with placebo, with 10 mg/day enalapril (by 6.0 and 8.5 mm Hg systolic and diastolic blood pressures) and 20 mg/day enalapril (by 7.7 and 5.0 mm Hg, respectively). Side effects were few and mild. No patient characteristic or drug effect correlated with changes in alcohol intake. There were no significant variations in nonalcoholic beverages, cigarette smoking, or body weight. These results indicate that enalapril does not alter alcohol intake in normotensive alcoholics with normal plasma renin activity. Studies with higher doses of enalapril in humans may be limited by increased frequency and severity of side effects.

Persistent Alterations of Vasopressin and N‐Terminal Proatrial Natriuretic Peptide Plasma Levels in Long‐Term Abstinent Alcoholics

“…The renin-angiotensin-aldosterone system seems to be involved in the regulation of alcohol consumption and tolerance, at least in rats (Grupp, 1991;Grupp et al, 1997;Naranjo et al, 1991;Spinosa et al, 1988). Aldosterone stimulates renal reabsorption of sodium and potassium excretion.…”

Role of Angiotensin Ii and the Subfornical Organ in the Pharmacological Actions of Ethanol

“…Kraly and Jones (1999) also could not support the hypothesis that Ang II provides an inhibitory physiological control of ingestion of ethanol, and in fact demonstrated that losartan significantly inhibited alcohol intake in a two-bottle drink test. Finally, the work of Grupp and colleagues that hypothesized that Ang II reduced alcohol intake was tested in alcoholic humans and the results of that study were negative (Naranjo et al, 1991). These data may be reconciled by the hypothesis that only a prolonged increase in central Ang II and/or an upregulated central RAS is stimulatory to ethanol intake in rats.…”

Efecto de la inhibición de la síntesis de angiotensina II en el consumo de alcohol

“…El sistema renina-angiotensina central parece ser uno de los moduladores del consumo de alcohol 2 ; en efecto, estudios experimentales muestran que los inhibidores de la enzima convertidora de la angiotensina I en II, tales como el captopril 3 , enalapril 4 y el abutapril 5 disminuyen la ingestión de etanol y que la inyección directa de captopril en el órgano fornical de estos animales produce una reducción de su consumo 6 . Sin embargo, algunos trabajos clínicos comunican que estos fármacos no modifican el consumo de etanol en alcohólicos 7 .…”

“…Durante las dos primeras semanas, período basal sin tratamiento farmacológico y previa instrucción de una ficha de monitoreo a utilizar, los pacientes anotaron su ingestión diaria de bebidas alcohólicas la cual fue expresada como tragos alcohólicos estándar (TAS), correspondiendo 1 TAS a 13,6 g de etanol absoluto. Esta forma de automonitoreo retrospectivo es acertadamente confiable y ha sido validado previamente por otros estudios clínicos 7 . Los pacientes también midieron la intensidad de su craving por alcohol, es decir, su sensación de búsqueda compulsiva y sostenida por esta droga.…”