madman
Super Moderator
The association of erectile dysfunction (ED) and cardiovascular disease is well-documented in the literature and both conditions share risk factors. Therefore, it is difficult to distinguish the effect of the underlying disease and adverse effects of the drugs and=or interactions between ED drugs and drugs implemented for cardiovascular disease. The known interactions of systemically administered drugs for ED with drugs for cardiovascular disease are mainly pharmacodynamic. Thus, nitrates enhance the production of cyclic GMP, and combined with phosphodiesterase type-5 inhibitors this can lead to severe hypotension. The same is the case for the treatment with phentolamine in patients treated with b-adrenoceptor antagonists. Due to increased partial thromboplastin time, the risk of bleeding is enhanced for intracavernous alprostadil injection in heparin-treated patients. Pharmacokinetic interactions of clinical importance have been described for ED drugs with other therapeutic groups such as sildenafil with the antifungal drug, ketoconazole, and apomorphine with the antiparkinson drug, entacapon. Although sildenafil and antihypertensive dihydropyridines like amlodipine are metabolized by the same cytochrome P450 enzyme, CYP3A4 in the liver, the combination of these drugs does not exhibit a synergistic blood pressure-lowering action. Unfortunately, documentation concerning drug interactions is often poor and occasional.
Introduction
Male erectile dysfunction (ED) is defined as the inability to attain or maintain penile erection sufficient for satisfactory sexual performance. The prevalence was > 50% in self-reported community-based respondents sampled between the ages of 40 and 70 y.1,2 The prevalence of complete ED increases with age from 5% at 40 to 15% at 70 y.1 The incidence rate for ED is 26 cases per 1000 man-years indicating it is important public health problem3
Alterations in the flow of blood to and from the penis are thought to be the most frequent causes of male ED. Therefore, erectile dysfunction can be considered to be another manifestation of vascular disease. ED is frequent in patients with other signs of atherosclerotic disease such as ischaemic heart disease and arterial leg disease,1,4,5 and ED and cardiovascular disease share the same risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking.1–3 The presence of several risks factors increase the risk of heart disease6 and ED.7,8 Moreover, a low penile brachial pressure index was found to be associated with major vascular events such as myocardial infarction and cerebrovascular accidents,9 ED is related to the presence of intermittent claudication10 Therefore, patients seeking health care for ischaemic heart disease will often have or develop ED and doctors should be aware of general cardiovascular disease in patients with ED.
The fact that the prevalence of ED in patients with cardiovascular disease is higher than in the general population also implies that patients, in addition to treatment for ED, are also treated for both heart disease, hypertension, diabetes, and=or dyslipidemia. This increases the risk that drug treatments for ED can affect cardiovascular function and treatments for cardiovascular disease can lead to ED. Adverse effects and drug interactions account for approximately one-third of the cases referred to a department of internal medicine11 and the same numbers are probably true for patients presenting with ED.
*The present review will focus on the effects of drugs for cardiovascular disease on erectile function and make special emphasis on the interactions of drugs for the treatment of ED with drugs for the treatment of heart disease.
Drugs for cardiovascular disease and erectile dysfunction
Drugs for cardiovascular disease and erectile dysfunction. The impact of cardiovascular drugs on erectile function is established in some cases, but in many others, the evidence is anecdotal and based on case reports. Rather than improving erectile function most of these studies suggest that treatment of cardiovascular disease worsens erectile function. Thus, in epidemiological studies, the relative risk for ED in hypertension and heart disease was increased, respectively, from 1.13 and 1.54 in untreated to 1.52 and 1.96 in treated patients.3 However, these figures do not allow to distinguish whether the patients have ED due to underlying generalized vascular disease or if erectile function deteriorates as a consequence of treatment with drugs for cardiovascular disease.
Pharmacological treatment of hypertension and erectile function
Thiazide diuretics, beta-adrenoceptor antagonists, calcium channel blockers, ACE inhibitors, and angiotensin II receptor antagonists are considered first-line drugs for the treatment of hypertension (Table 1).12 The goal of antihypertensive treatment, in addition to lowering blood pressure, is to reduce the risk of cardiovascular events. There is little trial-based evidence to indicate which of the hypertensive drugs are more likely to cause ED.
Treatment of heart disease and erectile dysfunction
An array of drugs are applied for the treatment of heart disease. In most cases, a multiple drug regimen is applied for conditions such as chronic heart failure, where patients are treated with diuretics for removal of surplus liquid, ACE inhibitors and=or AT1 receptor antagonists to cause peripheral vasodilation, digoxin as a positive inotropic agent, antithrombotics, antiarrhythmics, anticoagulants, and hypolipidemic drugs (Table 1).43 In addition, the aldosterone receptor antagonist, spironolactone, and b-adrenoceptor antagonists such as metoprolol, bisoprolol, and carvedilol were recently found to enhance survival in patients suffering from heart failure.44 – 46 Nitrates relieve pain, but they have not been shown to prolong survival in chronic heart failure unless they are taken in combination with the peripheral vasodilator, hydralazine.47 Evidence regarding the effect on erectile function of most of these drugs is sparse.
Interactions between drugs for erectile dysfunction and for cardiovascular disease
There are several treatment options for ED as outlined in Table 1. Although these drugs have different mechanisms of action, all drugs for ED reaching sufficiently high plasma concentrations have in common the potential of inducing systemic hypotension. Therefore, pharmacodynamic interactions enhancing the systemic vasodilator effect or pharmacokinetic interactions leading to accumulation of the drug applied for the treatment of ED are of major concern.
*Apomorphine and drugs for cardiovascular disease
*a-Adrenoceptor antagonists and drugs for cardiovascular disease
*Phosphodiesterase type-5 inhibitors and drugs for cardiovascular disease
*Alprostadil and drugs for cardiovascular disease
Introduction
Male erectile dysfunction (ED) is defined as the inability to attain or maintain penile erection sufficient for satisfactory sexual performance. The prevalence was > 50% in self-reported community-based respondents sampled between the ages of 40 and 70 y.1,2 The prevalence of complete ED increases with age from 5% at 40 to 15% at 70 y.1 The incidence rate for ED is 26 cases per 1000 man-years indicating it is important public health problem3
Alterations in the flow of blood to and from the penis are thought to be the most frequent causes of male ED. Therefore, erectile dysfunction can be considered to be another manifestation of vascular disease. ED is frequent in patients with other signs of atherosclerotic disease such as ischaemic heart disease and arterial leg disease,1,4,5 and ED and cardiovascular disease share the same risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking.1–3 The presence of several risks factors increase the risk of heart disease6 and ED.7,8 Moreover, a low penile brachial pressure index was found to be associated with major vascular events such as myocardial infarction and cerebrovascular accidents,9 ED is related to the presence of intermittent claudication10 Therefore, patients seeking health care for ischaemic heart disease will often have or develop ED and doctors should be aware of general cardiovascular disease in patients with ED.
The fact that the prevalence of ED in patients with cardiovascular disease is higher than in the general population also implies that patients, in addition to treatment for ED, are also treated for both heart disease, hypertension, diabetes, and=or dyslipidemia. This increases the risk that drug treatments for ED can affect cardiovascular function and treatments for cardiovascular disease can lead to ED. Adverse effects and drug interactions account for approximately one-third of the cases referred to a department of internal medicine11 and the same numbers are probably true for patients presenting with ED.
*The present review will focus on the effects of drugs for cardiovascular disease on erectile function and make special emphasis on the interactions of drugs for the treatment of ED with drugs for the treatment of heart disease.
Drugs for cardiovascular disease and erectile dysfunction
Drugs for cardiovascular disease and erectile dysfunction. The impact of cardiovascular drugs on erectile function is established in some cases, but in many others, the evidence is anecdotal and based on case reports. Rather than improving erectile function most of these studies suggest that treatment of cardiovascular disease worsens erectile function. Thus, in epidemiological studies, the relative risk for ED in hypertension and heart disease was increased, respectively, from 1.13 and 1.54 in untreated to 1.52 and 1.96 in treated patients.3 However, these figures do not allow to distinguish whether the patients have ED due to underlying generalized vascular disease or if erectile function deteriorates as a consequence of treatment with drugs for cardiovascular disease.
Pharmacological treatment of hypertension and erectile function
Thiazide diuretics, beta-adrenoceptor antagonists, calcium channel blockers, ACE inhibitors, and angiotensin II receptor antagonists are considered first-line drugs for the treatment of hypertension (Table 1).12 The goal of antihypertensive treatment, in addition to lowering blood pressure, is to reduce the risk of cardiovascular events. There is little trial-based evidence to indicate which of the hypertensive drugs are more likely to cause ED.
Treatment of heart disease and erectile dysfunction
An array of drugs are applied for the treatment of heart disease. In most cases, a multiple drug regimen is applied for conditions such as chronic heart failure, where patients are treated with diuretics for removal of surplus liquid, ACE inhibitors and=or AT1 receptor antagonists to cause peripheral vasodilation, digoxin as a positive inotropic agent, antithrombotics, antiarrhythmics, anticoagulants, and hypolipidemic drugs (Table 1).43 In addition, the aldosterone receptor antagonist, spironolactone, and b-adrenoceptor antagonists such as metoprolol, bisoprolol, and carvedilol were recently found to enhance survival in patients suffering from heart failure.44 – 46 Nitrates relieve pain, but they have not been shown to prolong survival in chronic heart failure unless they are taken in combination with the peripheral vasodilator, hydralazine.47 Evidence regarding the effect on erectile function of most of these drugs is sparse.
Interactions between drugs for erectile dysfunction and for cardiovascular disease
There are several treatment options for ED as outlined in Table 1. Although these drugs have different mechanisms of action, all drugs for ED reaching sufficiently high plasma concentrations have in common the potential of inducing systemic hypotension. Therefore, pharmacodynamic interactions enhancing the systemic vasodilator effect or pharmacokinetic interactions leading to accumulation of the drug applied for the treatment of ED are of major concern.
*Apomorphine and drugs for cardiovascular disease
*a-Adrenoceptor antagonists and drugs for cardiovascular disease
*Phosphodiesterase type-5 inhibitors and drugs for cardiovascular disease
*Alprostadil and drugs for cardiovascular disease
