Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates.

Abstract

Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for treatment of male erectile dysfunction. Many patients with erectile dysfunction are also being treated for systemic hypertension and/or cardiovascular disease. In a double-blind, randomized, placebo-controlled, crossover trial, SL apomorphine 5 mg and placebo were administered on alternate days to 162 men who were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1) blockers, or short- or long-acting nitrates. Blood pressure and heart rate were measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter monitoring. The only potentially clinically significant interactions between SL apomorphine and the antihypertensive agents or short-acting nitrates were greater orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium channel blocker groups (-10 and -6 mm Hg vs placebo, respectively). Administration of SL apomorphine after dosing with long-acting nitrates resulted in significant decreases in blood pressure when patients were standing (mean systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most common adverse events with SL apomorphine were dizziness, nausea, and headache. Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension occurred in 2 patients each in the short- and long-acting nitrate groups. Thus, in patients receiving common antihypertensive agents and short-acting nitrates, as well as in most patients receiving long-acting nitrates, SL apomorphine at higher than recommended doses produced no clinically significant changes in heart rate or blood pressure greater than changes seen with SL apomorphine alone.

• Authors: T C Fagan, S Buttler, T Marbury, A Taylor, A Edmonds, SL APO Study Group
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 88 Issue 7 Pg. 760-6 (Oct 01 2001) ISSN: 0002-9149 [Print] United States
• PMID: 11589843 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Adrenergic beta-Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Calcium Channel Blockers
• Diuretics
• Dopamine Agonists
• Nitrates
• Apomorphine

Topics

• Administration, Sublingual
• Adrenergic alpha-Antagonists (administration & dosage)
• Adrenergic beta-Antagonists (administration & dosage)
• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage)
• Antihypertensive Agents (administration & dosage)
• Apomorphine (administration & dosage, therapeutic use)
• Calcium Channel Blockers (administration & dosage)
• Cross-Over Studies
• Diuretics (administration & dosage)
• Dopamine Agonists (administration & dosage, therapeutic use)
• Double-Blind Method
• Electrocardiography, Ambulatory
• Erectile Dysfunction (drug therapy)
• Heart Rate (drug effects)
• Humans
• Hypertension (drug therapy)
• Male
• Middle Aged
• Nitrates (administration & dosage)
• Treatment Outcome