Structure activity relationship of antihypertensive drugs and erectile

New Insights into Hypertension-Associated Erectile Dysfunction

structure activity relationship of antihypertensive drugs and erectile

Erectile Dysfunction - online medications and virtual doctor consultations. Indeed, it is my concern that this drug will be given to men who really need relationship . (low blood pressure) and is known to increase cardiovascular nerve activity. antihypertensive drugs, and sexual dysfunction could in fact be the result of a drug side dependent relationship combined with the prolongation of The effect of lifestyle modification on sexual activity has not been function. Structural and. Keywords: Erectile dysfunction, Hypertension, Antihypertensive drugs, Management, The etiology can be found in the structural and functional abnormalities of the In this context, it has been demonstrated that moderate physical activity can relationship between antihypertensive medication and sexual dysfunction has.

ED has a high prevalence around the world and a huge impact on quality of life of men and their partners [ 2 ]. With the increment of life expectation and aging of population, ED burden is supposed to increase in the upcoming years [ 3 ].

structure activity relationship of antihypertensive drugs and erectile

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. 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, ED 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 ].

As 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.

Management of erectile dysfunction in hypertension: Tips and tricks

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 ].

New Insights into Hypertension-Associated Erectile Dysfunction

After introduction of sildenafil in therapeutic market in [ 8 ], a revolution shook 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 mostly 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 understood 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 released 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 ED, if it 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.

Erectile dysfunction is common, and the risk of developing ED increases with age. Experts have estimated that erectile dysfunction affects 30 million men in the United States.

Treatments include psychotherapy, adopting a healthy lifestyle, oral PDE5 inhibitors ViagraLevitraCialisStendra, and Staxynintraurethral prostaglandin E1 MUSEintracavernosal injections prostaglandin E1 [Caverject, Edex], Bimix and Trimixvacuum is ongoing in the field of erectile dysfunction to find improved and effective therapies. About Viagra Viagra is a pill used to treat erectile dysfunction impotence in men. It can help many men who have erectile dysfunction get and keep an erection when they become sexually excited stimulated.

You will not get an erection just by taking this medicine. Viagra is taken approximately one-hour before sex. It is effective for about 4 hours. Sexual stimulation is still required to get an erection, but often times, less than would be normally required. It is recommended that it not be used more than once a day.

Our Philosophy - Viagra Erectile Dysfunction

With larger doses, some men developed a very unusual side-effect: Because Viagra does not cause an erection but simply makes it easier to get one, the most dangerous side effect of injectables which do cause an erection is avoided. Injections can cause a condition known as priapism where a man cannot lose his erection. This is a very dangerous condition that must be treated immediately, and can lead to permanent damage. Given that no chemical is being injected, Viagra also does not lead to scarring.

One point that needs to be emphasized is that difficulties with getting an erection occur to almost all men, at least some of the time. However, Viagra is designed for the approximately million men worldwide affected by long-term erectile dysfunction. In studies, the drug was effective across patients with erection problems attributed to diabetes, prostatectomy, spinal cord injury, psychological, and other causes. Indeed, it is my concern that this drug will be given to men who really need relationship or personal counseling.

Thus, many men will not get the help they really need. Difficulties with erections are often merely a symptom of underlying problems. If doctors merely hand out a pill, they will be doing men and their partners a great disservice. The other interesting thing about Viagra that no one is mentioning for fear that the drug will be abusedis that in many men, the drug allows them to maintain an erection even following multiple orgasms.

So, in a sense, Viagra may eventually be useful for treatment of premature ejaculation. As a matter of fact, if this really works, it will be premature ejaculators who win out -- they still maintain their erection, but get to have more orgasms! Another implication is that for men who have partial erections, or easily lose their erections, this drug may make it easier for them to use condoms and have safer sex.

Given the incredible risks some men take in not using a condom, this would seem to me to be a legitimate use for the drug. When a man is sexually aroused, the arteries in the penis relax and widen, allowing more blood to flow into the penis.

structure activity relationship of antihypertensive drugs and erectile

As the arteries in the penis expand and harden, the veins that normally carry blood away from the penis become compressed, restricting the blood flow out of the penis. With more blood flowing in and less flowing out, the penis enlarges, resulting in an erection.

Viagraalso known as Sildenafil, does not directly give a man an erection. As a matter of fact, sexual dysfunction is encountered more frequently that it is indeed believed underlining the need for a more proper and concrete assessment.

However, due to the complex etiologic and pathophysiologic nature of sexual dysfunction, exclusion of concomitant diseases and drugs should be the initial step when approaching a hypertensive patient with this clinical condition that is not receiving any antihypertensive medication. Consequently, a significant amount of neurological, psychiatric, urologic and endocrine disorders should be ruled out before vasculogenic sexual dysfunction is diagnosed.

When the diagnosis of vasculogenic sexual dysfunction has been carefully reached, physicians will have to come up with an effective treatment. Appropriate lifestyle measures and adoption of a healthier attitude could represent an initial, efficient and cost-effective treatment option[ 14 ]. This is due to the fact that traditional CV risk factors such as hypertension, physical inactivity-obesity, smoking and dyslipidemia have been consistently linked with endothelial and consequently sexual dysfunction[ 15 ].

Interestingly, the beneficial effect of physical exercise on sexual dysfunction seems to be independent of its favorable impact on the general cardiovascular profile[ 17 ]. In terms of caloric reduction, Mediterranean diet exerts a positive effect on sexual function parameters of patients with metabolic syndrome[ 18 ]. Several observational and clinical studieshave consistently associated antihypertensive medication with sexual dysfunction[ 20 ]. Whether one class of antihypertensive agents is associated exclusively or more with erectile dysfunction compared to another, however, is a difficult puzzle to solve as there are many other factors comorbid conditions, concomitant medications, personal characteristics to be taken into account at the same time.

In addition, erectile dysfunction has never been studied as the primary end-point before and as a result a definite causative relationship between antihypertensive medication and sexual dysfunction has never been proven.

Despite the existing controversies, available data so far imply the old generation b-blockers e. A luminous exception to the rule, nebivolol, is a newer agent of its class which significantly ameliorates erectile dysfunction through increased nitric oxide generation, an effect consistently demonstrated in recent studies[ 2526 ].

Diuretics, even on adjunct therapy, constitute another antihypertensive agent negatively associated with sexual function[ 27 - 29 ]. On the other hand, calcium antagonists and angiotensin converting enzyme inhibitors seem to demonstrate a neutral effect[ 30 - 32 ]. Interestingly, angiotensin receptor blockers ARBs by blocking the vasoconstrictive action of angiotensin II seem to positively affect erectile function and are thus regarded as a first-line treatment in hypertensive patients with erectile dysfunction[ 222533 - 35 ].

In such cases there will always be a question hovering over physicians head. Is hypertension per se, antihypertensive medication or both, the causative factors provoking sexual dysfunction[ 15 ]? Duration and severity of hypertension are undoubtedly associated with erectile dysfunction.

When antihypertensive medication comes to the fore, certain issues need to be carefully addressed. Like the case of untreated hypertensive patients, evaluation of sexual dysfunction in hypertensive patients under antihypertensive regime, should primarily exclude other concomitant diseases and pharmaceutical agents.

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  • Erectile Dysfunction and Hypertension: Impact on Cardiovascular Risk and Treatment

Moreover, even physicians seldom report the cases of sexual dysfunction associated with certain medications. When medically induced sexual dysfunction is finally disclosed and a shift in medication is deemed necessary, b-blockers along with diuretics should generally be the first categories to be changed, unless they are deemed absolutely indicated for the individual patient.

Ideally, an ARB could constitute the mainstay of therapy in these cases. If sexual dysfunction still persists, then more effective remedies should be elected paving the way for the introduction of phosphodiesterase-5 inhibitors PDE PDE-5 inhibitors Since their introduction in the therapeutic field, more than a decade ago, PDE-5 inhibitors have revolutionized the treatment of sexual dysfunction.

By blocking the activity of PDE-5 isoenzyme, localized throughout the smooth muscle cells of the vasculature genital vessels includedPDE-5 inhibitors increase the levels of cyclic guanosine monophosphate thus exerting vasodilating properties and facilitating penile erection[ 40 - 42 ].

Due to these properties, sildenafil was the first drug of its class to receive wide acceptance. Its short half-life, food interactions and the associated visual disturbances however, paved the way for the development of newer PDE-5 inhibitors. As such vardenafil with its more rapid onset of action, and tadalafil with its longer half-life and the lack of food interactions or side effects, have offered significant alternatives to sildenafil[ 43 - 50 ].

Due to their vasorelaxing effect, administration of PDE-5 inhibitors in hypertensive individuals was initially confronted with great suspicion. A wealth of clinical data however has proven that PDE-5 inhibitors are associated with few side effects and provoke a small and insignificant reduction in blood pressure with minimal heart rate alterations in both normotensive and hypertensive patients as well. As a matter of fact, they can be safely and effectively administered to hypertensive individuals even when they are already taking multiple antihypertensive agents[ 51 - 56 ].

The sole exception to the rule is co-administration with organic nitrates, which is an absolute contraindication due to profound and possibly hazardous hypotension effect[ 5758 ]. Moreover, precaution should be taken when PDE-5 inhibitors are combined with a-blockers where, due to possible orthostatic hypotension effect, lower starting doses should be implemented in the therapeutic regime[ 59 - 62 ]. Apart from their beneficial effect in erectile dysfunction and their safe profile in antihypertensive medication, PDE-5 inhibitors have even more advantages to demonstrate.

Moreover, a handful of clinical data has demonstrated the considerable vasodilating and anti-proliferative properties of PDE-5 inhibitors in the pulmonary vasculature, establishing them as a first-line treatment in patients with pulmonary arterial hypertension[ 6566 ].

The same properties have been considered as potentially responsible for improving microcirculation in patients with secondary Raynaud phenomenon and ameliorating cardiopulmonary exercise performance in patients with heart failure[ 6768 ].

structure activity relationship of antihypertensive drugs and erectile

The common pathophysiologic substrate between erectile dysfunction and BPH-LUTS has rendered PDE-5 inhibitors an effective treatment which significantly improves measures of both conditions while at the same time exhibits high efficacy and safety.

The beneficial effect is much more pronounced when taking into consideration the fact that a-blockers, the mainstay of therapy for benign prostate hyperplasia frequently provoke sexual side effects, erectile dysfunction included[ 69 ]. Management beyond PDE-5 inhibitors Despite remarkable therapeutic efforts, it is evident that a relative proportion of patients with erectile dysfunction will fail to respond to oral pharmacotherapy including PDE-5 inhibitors.

The management of non-responders calls for second and third-line treatment implementation. Surgical implantation of a penile prosthesis, either the inflatable 2- and 3-piece or the malleable device, is a feasible technique that offers a third-line treatment and a more permanent solution to the problem of erectile dysfunction.

Interestingly, prosthesis implantation receives a significantly high satisfaction rate as evidenced by the proportionate scores in sexual satisfaction scales. Mechanical failure and infection are the two major disadvantages of those prosthetic implants however, their great efficacy, safety and satisfaction rate in general render them an attractive solution when conservative treatment fails[ 70 - 74 ].

structure activity relationship of antihypertensive drugs and erectile

Towards this direction, several sufficiently powered studies have demonstrated a higher incidence of erectile dysfunction in patients with coronary artery disease, either asymptomatic or overt. Moreover, in such patients erectile dysfunction is connected to the number of occluded vessels and more interestingly occurs over three years before coronary artery disease becomes apparent[ 76 - 80 ]. Several other facts support the close relationship between sexual dysfunction and CV disease. Endothelial dysfunction mediated by decreased nitric-oxide bioavailability as well as atherosclerotic lesions constitute a common pathophysiologic substrate affecting both CV disease and erectile dysfunction, a disease considered to be primarily of vascular origin[ 7680 - 82 ].

structure activity relationship of antihypertensive drugs and erectile

Several traditional CV risk factors diabetes mellitus, hypertension, dyslipidemia, and smoking are frequently found in individuals with erectile dysfunction, conferring a detrimental cardiovascular burden to them. More interestingly, the increased cardiovascular risk observed in those patients is independent of the aforementioned CV risk factors[ 81 - 88 ].

A recent systematic review and meta-analysis of relevant studies in this field confirmed that erectile dysfunction is associated with increased risk of CV events and all-cause mortality[ 89 ]. The pooled relative risks were 1. Of note, the relative risk was higher in intermediate-compared with high- or low-CV-risk populations and with younger age, with obvious clinical implications.

Since erectile dysfunction presents such an intimate relationship with CV parameters, it is easily deducted that it could constitute a powerful tool for detecting asymptomatic CV disease. Accordingly, the working group of the third Princeton Consensus Conference developed practical guidelines and a simplified algorithm in order to manage sexual dysfunction and sexual activity implementation issues in patients with different levels of CV risk, including hypertensive patients[ 90 ].

In particular, patients are classified into three categories low, intermediate, high depending on their CV risk profile. Moreover, patients of this group can safely initiate or reinstitute sexual activity without any need for additional cardiovascular evaluation. On the contrary, patients with uncontrolled hypertension poorly controlled, untreated, accelerated or malignant belong to the high risk group where both treatment of sexual dysfunction and sexual activity resumption must be deferred until a thorough and specialized evaluation and stabilization has primarily been made.

Erectile dysfunction usually precedes cardiovascular events by 3 to 5 years. Therefore, sexual function should be incorporated into cardiovascular disease risk assessment for all men. Recently, algorithms for the management of patients with erectile dysfunction according to the risk for sexual activity and future cardiovascular events were proposed[ 91 ]. A comprehensive approach to cardiovascular risk reduction comprising of both lifestyle changes and pharmacological treatment will result in significant benefits on overall vascular health, including sexual function.