title: 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.affiliation: Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA. TCFAGANMD@aol.com
authors.forename: T C
authors.initials: TC
authors.lastname: Fagan
authors.forename: S
authors.initials: S
authors.lastname: Buttler
authors.forename: T
authors.initials: T
authors.lastname: Marbury
authors.forename: A
authors.initials: A
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Edmonds
mesh_terms: D000286:Administration, Sublingual; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001058:Apomorphine / Q000008:administration & dosage / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D018491:Dopamine Agonists; D009566:Nitrates; D001058:Apomorphine