Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

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.     

Influence of Inhaled Corticosteroids and Dietary Intake on Bone Density and Metabolism in Patients With Moderate to Severe Asthma

Objectives Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. Design A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hospital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition RATE=15%).

Main outcome measures In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and γ-glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density.

Subjects Thirty-one patients with moderate to severe asthma who had been taking more than 1,000 μg beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 μg beclomethasone per day or the equivalent.

Statistical analyses performed Four factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients.

Results Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P<.05). Significant correlations (P<.02) were observed between bone density and calcium intake (r=.40), phosphorus intake (r=.35), protein intake (r=.30), and serum alkaline phosphatase level (r=−.30). Bone density was not significantly different between the two groups of patients with asthma.

Applications A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained. J Am Diet Assoc. 1997;97:1401–1406.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).