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Pharmacology chapter 44 antihypertensives and sexual dysfunction

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Erectile dysfunction ED is a common complaint in hypertensive men and can represent a systemic vascular disease, an adverse effect of antihypertensive medication or a frequent concern that may impair drug compliance. ED has been considered an early marker of cardiovascular disease. The connection between both conditions seems to be located in the endothelium, which may become unable to generate the necessary dilatation in penile vascular Pharmacology chapter 44 antihypertensives and sexual dysfunction in response to sexual excitement, producing persistent impairment in erection.

On the other hand, the real influence of antihypertensive drugs in erectile function Pharmacology chapter 44 antihypertensives and sexual dysfunction deserves discussion. Therefore, regardless of ED mechanism in hypertension, early diagnosis and correct approach of sexual life represent an important step of cardiovascular evaluation which certainly contributes for a better choice of hypertension treatment, preventing some complications and restoring the quality of life.

Erectile dysfunction ED has been defined according to National Institute Pharmacology chapter 44 antihypertensives and sexual dysfunction Health from as the persistent inability to reach or maintain and penile rigidity enough for Pharmacology chapter 44 antihypertensives and sexual dysfunction satisfaction [ 1 ].

ED has a high prevalence around the world and a huge impact on quality of life of men and their partners [ 2 Pharmacology chapter 44 antihypertensives and sexual dysfunction. With the increment of life expectation and aging of population, ED burden is supposed to increase in the upcoming Pharmacology chapter 44 antihypertensives and sexual dysfunction [ 3 ]. Actually, vasculogenic ED is considered part of a systemic vasculopathy and has a known relation with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking.

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ED has been considered an early marker of cardiovascular risk that could precede traditional clinical manifestations of atherosclerosis, indicating the presence of vascular disease.

In addition, Pharmacology chapter 44 antihypertensives and sexual dysfunction could alert clinicians to the presence of unknown risk factors and an increased cardiovascular risk. Thus, ED could offer the opportunity to implement adequate therapeutic efforts to minimize the burden of major cardiovascular disease such as myocardium infarction and stroke [ 4 ].

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Pharmacology chapter 44 antihypertensives and sexual dysfunction ED is highly prevalent and deeply impacts overall health of sexually active men, sexual function should be part of anamneses in all hypertensive subjects, especially those over 50 years.

Ideally, such investigation could be held before starting therapeutic. To stimulate this attitude, the main objectives of this paper are to review some aspects linking ED and hypertension, including arterial hypertension as a risk factor for ED, ED as a marker of cardiovascular risk, ED and antihypertensive drugs, its possible negative impact in therapeutic adhesion, and lastly, actual therapeutic approach of hypertensive men with ED.

Those numbers were similar in more recent publications over the world [ 5 ] and also in developing countries [ 6 ], projecting the assumption that over 30 million American citizens suffer from some level of sexual dysfunction [ 5 ].

Prevalence's numbers vary according to characteristics of the population studied and the method used to access erectile function. Some trials have used a single question about sexual satisfaction while others have adopted validated questionnaires like International Index of Erectile Function IIEF that could check all five major domains of sexuality: The most frequent reasons for such passiveness were belief that lack of complete erection was part of a normal aging, sexual inactivity caused by widowhood, lack of perception of ED as a medical disorder, ashamed to talk with a doctor about sexuality, lack of an effective treatment for most cases.

Probably the real impact of ED was even greater with a strong relationship with aging and some authors estimated that almost half of year-old men live with some degree of ED [ 56 ]. After Pharmacology chapter 44 antihypertensives and sexual dysfunction of sildenafil in therapeutic market in [ 8 ], a revolution Pharmacology chapter 44 antihypertensives and sexual Pharmacology chapter 44 antihypertensives and sexual dysfunction this scenario and search for offices increased as well as medical knowledge about ED and the way physicians treat their patients [ 9 ].

From the label of having an psychological illness to an exhaustive, invasive and Pharmacology chapter 44 antihypertensives and sexual dysfunction usefulness series of complementary exams, the evaluation post-PDE5 inhibitors turned to a simple identification of risk factors [ 10 ], their control whenever possible, and improvement of sexual performance through PDE5 inhibitors prescriptions [ 11 ] that quickly became one sales blockbuster.

As a consequence of PDE5 inhibitors basic development studies, erectile process was better Pharmacology chapter 44 antihypertensives and sexual dysfunction and several papers from the last decade stressed the association between ED and vascular disease identified by functional and structural changes related to atherosclerosis process [ 12 ]. These evidences, in addition to the mechanism of action of such drugs—based on dilation of muscular layers of arteries and cavernous spaces by the blockage of cyclic GMP degradation—point out ED as part of a generalized vasculopathy [ 13 ].

It seems important to remember the complexity of erection physiopathology as well as of the hypothetical link with cardiovascular disease—endothelial dysfunction—since multiple factors could cause ED and interfere in the delicate balance of mediators Pharmacology chapter 44 antihypertensives and sexual dysfunction from endothelium [ 14 ].

But psychological aspects of man sexuality interfere in all steps of sexual disorders and could complicate diagnostic attempts or harm therapy efforts. It is really important to individualize each complain in order to understand the situation and offer the best medical approach.

New therapeutic strategies and molecular targets will help to improve quality of erections and sexual satisfaction. In order to cure Pharmacology chapter 44 antihypertensives and sexual dysfunction, if Pharmacology chapter 44 antihypertensives and sexual dysfunction is really possible, some recent studies propose regular use of drugs with proved endothelial action such as statins or PDE 5 inhibitors, taken daily instead of on demand [ 15 ], in order to provide sensation of been always ready for intercourse.

Medical advances apart, the best treatment for ED remain its prevention. In this sense, men knowledge about cardiovascular health and the relationship of ED Pharmacology chapter 44 antihypertensives and sexual dysfunction traditional risk factors should help physicians Pharmacology chapter 44 antihypertensives and sexual dysfunction motivate therapeutic adhesion and adoption of a healthier way of life [ 16 ].

Several traditional Pharmacology chapter 44 antihypertensives and sexual dysfunction factors were related to ED in medical literature with some evidences Pharmacology chapter 44 antihypertensives and sexual dysfunction from well designed epidemiological trials.

Age seems to be the clearest risk factor with strong association with the presence and severity of ED [ 5 ]. After adjusting for age, the correlation between ED and modifiable risk factors—hypertension, diabetes, hyperlipidemia, obesity, sedentary, and smoking—remained significant [ 17 ].

The increase of ED's prevalence with aging is Pharmacology chapter 44 antihypertensives and sexual dysfunction chapter 44 antihypertensives and sexual dysfunction by atherosclerotic lesions in vascular tree [ 18 ].

Most men with hypothetic vasculogenic ED present at least one traditional cardiovascular risk factor [ 19 ]. These evidences allowed the consideration of ED as a clinical manifestation of a functional lack of vasodilation or structural abnormality Pharmacology chapter 44 antihypertensives and sexual dysfunction penile circulation as component of a systemic vasculopathy [ 20 ]. Erection is a complex psiconeurovascular process and involves several system interactions that converge to an increase in hypogastrian-penian blood flow and subsequent activation of veno-occlusive mechanism of corpus cavernosum [ 21 ].

It is well Pharmacology chapter 44 antihypertensives and sexual dysfunction that the blood increment towards cavernous tissues necessary for a rigid erection is huge and even small hemodynamic disturbances could produce sexual dysfunction [ 22 ]. So, traditional risk factors such as hypertension, diabetes, and hyperlipidemia could contribute for ED development or worsening even in situations where psychological etiology seems more likely. In addition, penile erectile tissue's integrity depends on oxygen tension fluctuations that occur during physiologic erections.

As a consequence of regular erections, several cytokines, vasoactive, and growth factors keep a suitable environment for erectile tissue with a protective effect over stroma and muscular cells of this region [ 23 ].

In a pathological condition causing the absence of stimulated or physiological erections and abolishing such stimulus, there would be a structural change in tissue composition with deleterious consequences on erectile capacity [ 24 ]. Some trials have shown the presence of vascular disease in men suffering from vasculogenic ED but without traditional risk factors, pointing out ED as a clinical early cardiovascular risk marker [ 25 ].

Particularly among men less than 60 years old, ED seems to act as a risk factor independent of traditional markers [ 26 ]. More recently, laboratorial markers such as dimetilarginin asymmetric ADMA [ 27 ] and C-reactive protein were reported higher in ED men when compared with Pharmacology chapter 44 antihypertensives and sexual dysfunction without ED and similar risk factors [ 28 ]. On the other hand, as a consequence of its multifactorial aspect, several conditions could promote ED without systemic vascular involvement such as pelvic surgeries, depression, Peyronie's disease, and prostatism.

Probably this aspect is one among others to explain the lack of additional contribution of ED over traditional risk factors Framingham score during cardiovascular evaluation in some reports [ 29 ].

Other possible explanations were the characteristics of study population, method of assessing risk factors and the diagnostic tool used for ED diagnostic. Other risk factors have been related to ED. Sedentarism, obesity, and smoking have been implicated in the etiology of ED, and an approach of these risk factors has been able to reverse ED and restore normal erectile function Pharmacology chapter 44 antihypertensives and sexual dysfunction 30 ].

Metabolic syndrome and waist-to-rip ratio have been associated to more severe ED among those over 50 years old [ 31 ]. Sleep disorders were also more prevalent among ED men and their treatment could help in recovering sexual satisfaction [ 32 ]. Hypertension is considered one of the Pharmacology chapter 44 antihypertensives and sexual dysfunction hazardous cardiovascular risk factors and it is a frequent comorbidity of men with ED [ 33 ]. One of the first studies to ask about sexual function among hypertensives was the classic TOMHS The Treatment of Mild Hypertension Study [ 34 ] Pharmacology chapter 44 antihypertensives and sexual dysfunction its results contributed Pharmacology chapter 44 antihypertensives and sexual dysfunction the false belief that ED was rare in this population since they found only TOMHS excluded subjects with comorbidities like diabetes or hyperlipidemia, older and moderate or severe hypertension.

1. Introduction

Other trials also refuse the high prevalence of ED among hypertensives Pharmacology chapter 44 antihypertensives and sexual dysfunction 35 ] probably due to characteristics Pharmacology chapter 44 antihypertensives and sexual dysfunction the sample and the method to diagnose ED.

On the other hand, Jensen et al. Burchardt and coworkers using IIEF-5 to access erectile function among hypertensive men, aging from 34 to 75 years old, found Recently, Chang et al. The association of ED and vascular risk factors including hypertension raises the hypothesis that endothelial dysfunction is the common link between erectile dysfunction and cardiovascular disease.

But a possible association between ED and hypertension is much more intricate issue involving other aspects, such as the hemodynamic interferences caused by antihypertensive drugs. There is a complex relationship among arterial hypertension and erectile dysfunction that is explained by the multifactorial pathophysiological process that take place in both conditions Figure 1. So, considering that it is still matter of discussion if hypertension is cause or consequence of endothelial dysfunction, it can influence ED severity or it could appear before ED.

Depending on the class of the antihypertensive drug and its effect over Pharmacology chapter 44 antihypertensives and sexual dysfunction mediators, the impact on ED could be positive or negative. Lack of efficacy could represent a more intense vascular damage.

Introduction

In contrast, continuous use of PDE5 inhibitors proved to reverse endothelial Pharmacology chapter 44 antihypertensives and sexual dysfunction with positive impact on Pharmacology chapter 44 antihypertensives and sexual dysfunction function and Pharmacology chapter 44 antihypertensives and sexual dysfunction on blood pressure control.

Relationship between hypertension and erectile dysfunction. In almost all trials where this topic was studied, ED was not the primary objective and was assessed by patient reports instead of questionnaire evaluation or measurement of penile rigidity. So, there is a lack of definitive evidence even with betablocker and diuretics.

ACE inhibitors, angiotensin receptor blockers, and calcium channel antagonists were reported Pharmacology chapter 44 antihypertensives and sexual dysfunction have no relevant or even a positive effect on erectile function [ 42 ].

Development of erectile dysfunction in connection with betablockers might be biased by psychological effects derived from the awareness of being treated with a certain substance. This is an important point since patient concerns about the adverse effects Pharmacology chapter 44 antihypertensives and sexual dysfunction drugs on erectile function might limit the use of essential medications in cardiovascular high-risk patients [ 43 ].

In the same way, data with diuretics and ED are not conclusive. A small number Pharmacology chapter 44 antihypertensives and sexual dysfunction patients and inadequate evaluation of erectile function limit the trials results. It is important to consider that drugs used for treatment of cardiovascular diseases have often been accused of influencing erectile function, and such belief could influence drug compliance [ 42 ].

Some authors do Pharmacology chapter 44 antihypertensives and sexual dysfunction agree with a class specific and Pharmacology chapter 44 antihypertensives and sexual dysfunction effect over erectile function [ 45 ]. Others believe that the hypotensive effect of any drug could produce ED in susceptible subjects with comorbidities [ 36 Pharmacology chapter 44 antihypertensives and sexual dysfunction. More recently, Earden et al.

On Pharmacology chapter 44 antihypertensives and sexual dysfunction other hand, small studies suggested that some antihypertensive drug classes Pharmacology chapter 44 antihypertensives and sexual dysfunction have less harmful or even beneficial effect on sexual function like calcium channel antagonists [ 47 ], angiotensin Pharmacology chapter 44 antihypertensives and sexual dysfunction receptor blockers [ 44 ], and nebivolol [ 45 ].

There is no clinical trial evaluating the effect of calcium channel antagonists on erectile function with an adequate assessment of ED, but they are reported to have no relevant effect on erectile function [ 47 ].

For drugs that act over renin-angiotensin system, most evidence suggests that there was no influence on erectile function, and some authors indicate beneficial Pharmacology chapter 44 antihypertensives and sexual dysfunction [ 42 ].

Favorable effects on nitric oxide synthase and oxidative stress have been shown with nebivolol pointing out a mechanism for improvement of erectile function.

Experimental studies have demonstrated an enhancement of endothelial function in aorta and corpus cavernosum with a significant reduction in penile oxidative stress and collagen content [ 49 ], protected cavernosal tissue against structural changes, and increased expression of endothelial NO synthase eNOS [ 50 ].

Although no class of antihypertensive agents presents a clearly superior effect over the others in terms of quality of life, the current impression is that nebivolol, ACE inhibitors, and angiotensin II receptor antagonists may offer some advantage, at least in regard to effects on cognitive function and sexual activity [ 51 ]. The presence of comorbidities and concomitant drugs, a common situation in older hypertensive subjects, and lack of diagnostic standardization concerning tools to access erectile function impair a reliable analysis of trials about the relationship between ED and hypertension as well as any robust conclusion about deleterious action of antihypertensive drugs on erectile function [ 52 Pharmacology chapter 44 antihypertensives and sexual dysfunction. In this way, search for new data on basic mechanism under ED development in hypertensive individuals is an actual need.

In an individual aspect, sexual activity and erectile function quality should be part of anamnesis before starting antihypertensive therapy and seems to play a relevant role in the followup, as it would allow a scalable monitoring of erectile function, help the selection of better classes of antihypertensive drugs, turn easier the identification of adverse sexual events, and even improve therapeutic compliance [ 51 ].

Several hypotheses try to explain the pathophysiology of ED in hypertensive individuals. Since the pioneering work of Jeremy et al. Old and more recent experimental studies have pointed out the role of nitric oxide NO and other possible mediators in endothelial dysfunction of hypertensive rats [ 56 ].

In spontaneously hypertensive rats, endothelial-mediated relaxation of corporal Pharmacology chapter 44 antihypertensives and sexual dysfunction strips in response to acetylcholine was significantly impaired, suggesting a defect in endothelium-dependent reactivity and a corresponding reduction in NO [ 57 ].

On the other hand, decrease in NO production or bioavailability would take place in the etiology of hypertension in several Pharmacology chapter 44 antihypertensives and sexual dysfunction situations [ 59 ] where ED is not always present.

Thus, one possible mechanism by which hypertension may cause ED is likely related to endothelial dysfunction associated with hypertension.

Long-standing hypertension may cause oxidative stress, endothelial cell injury, and its consequences, including the inability of arteries, arterioles, and sinusoids of the corpus cavernosum to dilate properly [ 60 ]. Some authors state that ED symptoms in hypertensive patients would represent deterioration in endothelial dysfunction already present and should alert for a possible progression of a systemic vasculopathy [ 61 ].

Corroborating this link among hypertension and ED, Vlachopoulos et al. They suggested NO bioavailability reduction Pharmacology chapter 44 antihypertensives and sexual dysfunction by ADMA accumulation consequent of high blood pressure as the molecular mechanism for these findings.

This and other authors [ 63 ] argue that ED should represent a clinical sign of a deeper vascular damage in hypertensive patients and an increased risk of cardiovascular events.

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