enalapril and Cerebral-Hemorrhage

A 66-year-old hypertensive male with acute intracerebral hemorrhage developed acute hyponatremic coma 3 days after the addition of enalapril and a combination of amiloride and a thiazide diuretic to his hypotensive regimen. The patient recovered consciousness and serum sodium normalized 2 days after fluid restriction and withdrawal of both medications. Three weeks later, upon inadvertent reinstitution of enalapril and indapamide, severe hyponatremic encephalopathy promptly recurred; recovery was again rapid following fluid restriction and withdrawal of both medications. This temporal relationship establishes the thiazide diuretic or the angiotensin converting enzyme inhibitor or both as the cause of the profound symptomatic hyponatremia in this patient. Results of simultaneous serum and urine osmolality assays on several occasions were consistent with a decrease in free water clearance, a result of either increased antidiuretic hormone (ADH) secretion or potentiation of its peripheral action, and thiazide-induced natriuresis. The use of a thiazide diuretic in the presence of either of these aberrations of ADH homeostasis most likely explains the profound and rapid development of hyponatremia. Drug-induced disturbances in serum osmolality are a potentially reversible cause of deterioration of the mental state in a patient with an acute cerebrovascular accident.

Topics: Aged; Amiloride; Benzothiadiazines; Central Nervous System; Cerebral Hemorrhage; Coma; Diuretics; Enalapril; Humans; Hypertension; Hyponatremia; Indapamide; Male; Osmolar Concentration; Sodium; Sodium Chloride Symporter Inhibitors; Vasopressins; Water

1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1 receptor antagonist; losartan, in which a major active metabolite is a non-competitive angiotensin AT1 receptor antagonist; and enalapril, an angiotensin-converting enzyme inhibitor, using the salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10 mg/kg per day), losartan (10 mg/kg per day) and enalapril (10 mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt-loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to > 90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion). 4. Competitive (ME3221) and non-competitive (losartan) angiotensin AT1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt-loaded SHRSP; both were more potent than enalapril in the protective effect.

Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Body Weight; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Enalapril; Hypertension; Imidazoles; Losartan; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazoles

We present the case of a child who died of pulmonary hypoplasia as a result of the oligohydramnios sequence. The mother was taking enalapril, as well as propranolol and hydrochlorothiazide, for treatment of hypertension associated with systemic lupus erythematosus. Autopsy examination revealed severe renal tubular malformation. Correlation of animal data with previous case reports of neonatal anuria in association with maternal angiotensin converting enzyme inhibitors suggests that these agents may have a deleterious effect on fetal renal development and general well-being.

Topics: Amniotic Fluid; Cerebral Hemorrhage; Cerebral Infarction; Enalapril; Female; Humans; Infant, Newborn; Kidney Glomerulus; Kidney Tubules; Male; Pregnancy; Prenatal Exposure Delayed Effects