enalapril and Alcoholism

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.

Topics: Adult; Aged; Alcoholism; Anxiety; Blood Pressure; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Smoking

Pharmacological and genetic interference with the renin-angiotensin system (RAS) seems to alter voluntary ethanol consumption. However, understanding the influence of the RAS on ethanol dependence and its treatment requires modeling the neuroadaptations that occur with prolonged exposure to ethanol. Increased ethanol consumption was induced in rats through repeated cycles of intoxication and withdrawal. Expression of angiotensinogen, angiotensin-converting enzyme, and the angiotensin II receptor, AT1a, was examined by quantitative reverse transcription polymerase chain reaction. Increased ethanol consumption after a history of dependence was associated with increased angiotensinogen expression in medial prefrontal cortex but not in nucleus accumbens or amygdala. Increased angiotensinogen expression also demonstrates that the astroglia is an integral part of the plasticity underlying the development of dependence. The effects of low central RAS activity on increased ethanol consumption were investigated using either spirapril, a blood-brain barrier-penetrating inhibitor of angiotensin-converting enzyme, or transgenic rats (TGR(ASrAOGEN)680) with reduced central angiotensinogen expression. Spirapril reduced ethanol intake in dependent rats compared to controls. After induction of dependence, TGR(ASrAOGEN)680 rats had increased ethanol consumption but to a lesser degree than Wistar rats with the same history of dependence. These data suggest that the central RAS is sensitized in its modulatory control of ethanol consumption in the dependent state, but pharmacological or genetic blockade of the system appears to be insufficient to halt the progression of dependence.

Topics: Adaptation, Physiological; Alcoholism; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Animals, Genetically Modified; Central Nervous System; Disease Models, Animal; Enalapril; Ethanol; Humans; Neuronal Plasticity; Rats; Rats, Wistar; Receptors, Angiotensin; Renin-Angiotensin System; RNA, Antisense

The overall prognosis for patients with congestive heart failure is poor. Defining specific populations that might demonstrate improved survival has been difficult. We therefore examined our patient database for patients with congestive heart failure who demonstrated sustained improvement in left ventricular function and associated resolution of signs and symptoms of congestive heart failure.. We identified 11 patients with severe congestive heart failure (average ejection fraction 21.9 +/- 4.23% (+/- SD) who developed spontaneous, marked improvement over a period of follow-up lasting 4.25 +/- 1.49 years. All 11 patients were initially symptomatic with exertional dyspnea and fatigue for a minimum duration of 3 months. They form a subset of a larger group of 97 patients with chronic congestive heart failure that we have followed with sequential ejection fraction measurements. All 11 patients were treated with digitalis diuretics, and either converting-enzyme inhibitors or a combination of isosorbide dinitrate and hydralazine. Ten of the 11 patients had a history consistent with chronic alcoholism, and each reportedly abstained from alcohol during follow-up.. During the follow-up period, the average ejection fraction improved in 11 patients from 21.9 +/- 4.23% to 56.64 +/- 10.22%. Late follow-up indicates an average ejection fraction of 52.6 +/- 8.55% for the group. Congestive heart failure resolved in each case.. We conclude that selected patients with severe congestive heart failure can markedly improve their left ventricular function in association with complete resolution of heart failure. This appears to be particularly evident in those patients with chronic alcoholism who subsequently abstain.

Topics: Aged; Alcoholism; Captopril; Digoxin; Diuretics; Enalapril; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Remission Induction; Stroke Volume

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.

Topics: Alcohol Drinking; Alcoholism; Animals; Blood Pressure; Captopril; Dose-Response Relationship, Drug; Enalapril; Ethanol; Rats; Rats, Inbred Strains; Renin