Enalapril

Cardiovascular

Of all studies of the effects of ACE inhibitors on mortality in acute myocardial infarction, only the CONSENSUS II trial did not show a positive effect. In this trial enalaprilat was infused within 24 hours after the onset of symptoms, followed by oral enalapril. The reasons for the negative result of CONSENSUS II remain unresolved, but hypotension linked to a poorer prognosis has been suggested as an explanation. In a small substudy of this large trial, 60 patients were investigated for residual ischemia before discharge, with exercise testing and Holter monitoring [ ]. Episodes of hypotension and predischarge ischemia were more common with enalapril than with placebo. The authors suggested that enalapril induced a proischemic effect in hypotension-prone patients, mediated through exacerbation of the hemodynamic response, since the initial blood pressure fall after myocardial infarction is related to residual ischemia and recurrent acute ischemic syndromes. This conclusion seems very speculative. The data were derived from a small substudy with multiple subanalyses and cannot support a cause-and-effect relation between the acute hemodynamic effect and the predischarge ischemic conditions. ACE inhibitors should still be used in acute myocardial infarction with cautious dose titration.

Respiratory

Obstructive sleep apnea is characterized by upper airway inflammation, and it has been postulated that ACE inhibitors, by inducing cough and rhinopharyngeal inflammation, may contribute [ ].

• A 64-year-old woman developed likely ACE inhibitor-induced cough and had evidence of moderate obstructive sleep apnea while taking enalapril 10 mg/day for hypertension. Her symptoms of cough and diurnal sleepiness resolved completely after enalapril withdrawal.

In view of this possible association a small-scale study of patients with obstructive sleep apnea taking ACE inhibitors was performed, assessing polysomnography and post-sleep exhaled nitric oxide (as a marker of airway inflammation). Withdrawal of ACE inhibitors produced significant polysomnographic improvement in patients who had ACE inhibitor-induced cough, and was associated with recovery of upper airway symptoms and normalization of exhaled nitric oxide concentrations. These results suggest that ACE inhibitors may contribute to obstructive sleep apnea, particularly in patients who develop cough and upper airway symptoms.

Neuromuscular function

Muscular weakness has been reported in a patient with mild renal impairment taking enalapril [ ].

• A 78-year-old man, taking enalapril (10 mg/day), furosemide, and digoxin for cardiac failure due to ischemic heart disease, suddenly developed generalized muscle weakness. He had grade 3/5 weakness of all four limbs, his cranial nerves were intact, and there was no sensory impairment. His tendon reflexes were reduced and he had flexor plantar reflexes. The initial diagnosis was Guillain–Barré syndrome. Further investigation showed peaked T waves on his electrocardiogram, with a serum potassium of 9.4 mmol/l and a creatinine of 266 μmol/l. He was treated with glucose plus insulin, calcium gluconate, and sodium bicarbonate. Enalapril was withdrawn. His potassium concentration normalized.

Hyperkalemic muscle paralysis has been reported in renal insufficiency and trauma and in patients taking spironolactone and amiloride plus hydrochlorothiazide (co-amilozide). ACE inhibitors inhibit the release of aldosterone, reducing renal potassium loss, which can be enhanced by potassium-sparing diuretics or pre-existing renal insufficiency.

Sensory systems

ACE inhibitors can cause taste disturbances.

• A 66-year-old man developed severe dysgeusia and impaired quality of life while taking enalapril 5 mg/day, having previously been intolerant of quinapril because of cough [ ].

This case illustrates the occurrence of different adverse effects of two antihypertensive drugs in the same class.

Endocrine

Cases of the syndrome of inappropriate secretion of antidiuretic hormone has been reported with enalapril [ , ].

Electrolyte imbalance

The management of hyperkalemia caused by inhibitors of the renin–angiotensin–aldosterone system has previously been reviewed [ ]. Volume depletion is a risk factor for the development of both renal impairment and subsequent hyperkalemia, because of the effects of ACE inhibitors on the renal vasculature. A further case of life-threatening hyperkalemia has been reported in a woman who developed a severe diarrheal illness on a background of widespread vascular disease, for which she was taking enalapril, bisoprolol, bumetanide, and isosorbide mononitrate [ ].