Factors related to first dose hypotensive effect of captopril: prediction and treatment.

Abstract

The blood pressure response to the first dose of captopril (6 25 mg, 12 5 mg, or 25 mg) was measured in 65 treated, severely hypertensive patients. Mean supine blood pressure was 187/108 mm Hg immediately before captopril was given. Twenty one patients experienced a fall in supine systolic pressure greater than 50 mm Hg, including five whose pressure fell more than 100 mm Hg and two whose pressure fell more than 150 mm Hg. Six patients developed symptoms of acute hypotension, including dizziness, stupor, dysphasia, and hemiparesis. Percentage reductions in blood pressure were greatest in those with secondary hypertension (p < 0-05), high pretreatment blood pressure (p < 0 05), and high concentrations of plasma renin and angiotensin II (p < 0 01). No significant correlation was found between fall in blood pressure and serum sodium concentration, age, renal function, and the dose of captopril given.A severe first dose effect cannot be consistently predicted in individual patients who have received other antihypertensive drugs for severe hypertension. Such patients should have close medical supervision for at least three hours after the first dose of captopril. IntroductionWhen the angiotensin converting enzyme inhibitor captopril is first given there is, within two hours, a fall in arterial pressure that is proportional to the concurrent fall in the plasma concentration of angiotensin II.' In some severely hypertensive patients this initial fall in blood pressure is precipitous.2-5 The incidence of this potentially dangerous event is unknown, and insufficient information is available to the clinician to aid in its anticipation and, if necessary, treatment.We report here a study of the hypotensive effect of the first dose of captopril in 65 consecutive patients admitted for treatment of resistant hypertension.

Tissue and plasma angiotensin converting enzyme and the response to ACE inhibitor drugs.

“…Marked hypotension has been documented in the setting of normal extracellular volume and sodium status, however (Hodsman et al, 1983). Tissue based vascular ACE may be the unquantified element in this haemodynamic response (Okamura et al, 1986).…”

The response to the first dose of an angiotensin converting enzyme inhibitor in uncomplicated hypertension‐a placebo controlled study utilising ambulatory blood pressure recording.

“…Early studies with these drugs used failure was reported to be associated with marked first high doses and this was associated with a spectrum of dose hypotension with concomitant organ hypoCorrespondence: Dr R. J. MacFadyen, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow Gll 6NT perfusion damage (Cleland et al, 1985;LaBarre et al, 1982;Lantz et al, 1984;Mujais et al, 1984). Although attempts have been made to define factors predicting such responses (Hodsman et al, 1983) there is no good discriminant of predisposition to a marked hypotensive response.…”

'First dose' hypotension and venodilatation [letter]

“…Profound falls in blood pressure may occur in some patients when commencing captopril or enalapril (Cleland et al, 1985;Hodsman et al, 1983). Although these 'first dose' hypotensive reactions may be asymptomatic, in some patients myocardial ischaemia, transient hemiparesis, dysphasias or coma have developed (Cleland et al, 1985;Hodsman et al, 1983;Packer et al, 1986;Todd & Heel, 1986;Webster, 1987); deaths have also occurred.…”

“…Although these 'first dose' hypotensive reactions may be asymptomatic, in some patients myocardial ischaemia, transient hemiparesis, dysphasias or coma have developed (Cleland et al, 1985;Hodsman et al, 1983;Packer et al, 1986;Todd & Heel, 1986;Webster, 1987); deaths have also occurred. Similar 'first dose' reactions have been described with phentolamine (Galloway et al, 1975), prazosin (Graham et al, 1976), ketanserin (Waller et al, 1987), labetalol (Maronde, 1983), renin inhibitors (Semple et al, 1988;Zusman et al, 1983), ,-adrenoceptor blockers and adrenergic neurone blockers (Kholeif & Isles, 1989;Webster, 1987).…”

“…Although venodilatation has long been suspected in 'first dose' reactions (Cleland et al, 1985;Hodsman et al, 1983;Webster, 1987), direct evidence remains scant. Captopril (and by implication enalapril) reduces venous tone by up to 50% in patients with heart failure (Awan & Mason, 1982;Cowley et al, 1982;Faxon et al, 1981).…”