The Choice of Antihypertensive Drugs in Patients with Erectile Dysfunction

Summary

It is well established that hypertension and the more traditional anti-hypertensive drugs are associated with erectile dysfunction (ED). There is evidence showing that two antihypertensive drugs - doxazosin and losartan - have a positive effect on erectile function. Therefore these drugs may decrease the incidence of ED in patients who need treatment for hypertension. Doxazosin

and/or losartan can also be beneficial in patients who develop ED after starting treatment with other antihypertensive drugs. These options could, in turn, ensure better compliance and blood pressure control. A fall in the overall cost of treatment will also be anticipated if there is a reduced need for drugs prescribed for ED in patients with hypertension.     

The treatment of hypertension in patients with erectile dysfunction

Hypertension is another predictor of erectile dysfunction (ED). This is further evidence supporting a link between the pathogenesis of atherosclerotic disease and ED. In one study (TOMHS) involving hypertensive patients, the incidence of ED was 14.4%. The drugs used to treat hypertension may cause ED. However, there is little trial-based evidence to indicate which drugs are more likely to cause this side effect. In general, thiazide diuretics and beta-blockers seem to cause ED more often. In contrast, the alpha-blocker, doxazosin, has not been associated with an increased incidence of ED as a side effect. Doxazosin also improves urinary flow in patients with benign prostatic hyperplasia (BPH). This condition is common in elderly men as is hypertension and ED. Therefore, doxazosin may present a special advantage among this group of patients. This alpha-blocker would also be a good choice in patients with impaired glucose tolerance/diabetes because it improves insulin sensitivity. Moreover, ED and hypertension are more prevalent among diabetics. On a more speculative note, doxazosin may potentiate the therapeutic impact of specific treatments for ED.     

Common therapeutic strategies in the management of sexual dysfunction and cardiovascular disease

Sexual dysfunction is a frequent complication of treated and untreated cardiovascular disease. In fact, approximately 30% of hypertensives have been found to suffer from erectile dysfunction (ED) resulting from arterial dysfunction. Recent evidence has suggested that ED may be an early indicator of subclinical cardiovascular disease. In women, the evidence is similar, but more limited, showing that in hypertensive patients there is an increased prevalence of sexual dysfunction involving decreased vaginal lubrication, decreased orgasm, and increased pain. Clouding the issue, however, is that some antihypertensive agents may induce sexual dysfunction in hypertensives with normal sexual function. In contrast to the chronic treatments used in hypertension, therapies for ED involve acute treatments (none currently approved for women) targeting vasodilation of penile arteries, resulting in erection. Common to the treatment of hypertension and ED is that the current therapies were not designed to target underlying disorders of local, neural, vascular, or endocrine origin. In fact, while blood pressure is lowered, and erectile responses are improved with the respective therapies, the causal abnormalities may progress thereby limiting the long-term effectiveness of the medication. Some antihypertensive agents have been shown to have additional effects beyond blood pressure reduction and their impact on sexual function is a key focus of this review. This review examines the current and future strategies for treatments of male and female sexual dysfunction and the potential for therapeutic modalities that go beyond the recovery of the responses by targeting the fundamental mechanisms common to both sexual dysfunction and cardiovascular disease.     

Cardiovascular effects of phosphodiesterase 5 inhibitors

Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are now approved for the treatment of erectile dysfunction. They inhibit the cGMP-specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which, for example in smooth muscle cells, reduces muscular tone. In the cardiovascular system, they slightly reduce arterial systemic blood pressure. This moderate effect was also shown in combination with many antihypertensive drugs. But the important contraindication is the concomitant use of PDE 5 inhibitors with any drug serving as a nitric oxide donor, as this combination can lead to significant arterial hypotension. Caution is needed in patients on alpha-blocking agents. In general, this class of drugs was not shown to exhibit direct deleterious effects on the myocardium or promote arrhythmias. Furthermore, statistical evaluations did not demonstrate an increased risk for patients taking PDE 5 inhibitors in comparison with an adequate control population. Many patients suffering from erectile dysfunction may be characterized by multiple cardiovascular risk factors or even ischemic heart disease, suggesting an increased baseline risk. While in many forms of erectile dysfunction, these agents seem to be very effective, it becomes clear that endothelial dysfunction is an attractive target of PDE 5 inhibitors and may also be the underlying cause in many types of erectile dysfunction. In addition, these agents seem to be very effective in lowering pulmonary arterial pressure, which might provide the opportunity to treat primary and some forms of secondary pulmonary hypertension, perhaps in combination with inhaled nitric oxide or other pulmonary arterial vasodilators. Sildenafil was approved for treatment of primary arterial hypertension in the U.S. in June 2005. Recently, direct cardioprotective effects were described in animal research, resembling preconditioning-like effects, which may, under certain conditions, also be applicable in clinical research.     

南阳地区高血压人群基因多态性与抗高血压药物个体差异性关系临床研究

目的：分析河南省南阳地区抗高血压药物相关基因分布特征,为该地区高血压患者个体化治疗提供参考,提高抗高血压治疗的经济效益。方法原发性高血压患者135例,通过Tap-man探针法对目前国内外已达成共识的五大类降压药疗效相关的13个基因位点进行检测,分析相关基因在不同人群的分布特征。结果（1）南阳地区高血压患者可能对氢氯噻嗪、氨氯地平、氯沙坦类药物疗效较好;（2）美托洛尔降压效果一般且发生心动过缓风险过高;（3）女性患者服用ACEI类药物后咳嗽风险明显高于男性,且效果较男性差（P＜0.05）;（4）肥胖高血压患者可能对氨氯地平效果较好（P＜0.05）。结论南阳地区的高血压患者可广泛应用氢氯噻嗪、氨氯地平、氯沙坦类药物;对美托洛尔效果可能较差,不建议广泛应用;女性患者不建议应用ACEI类药物;肥胖患者应用氨氯地平效果可能较好。     

A risk-benefit assessment of sildenafil in the treatment of erectile dysfunction.

Sildenafil is an oral treatment for erectile dysfunction (ED). It acts as an inhibitor of 3',5'-cyclic guanosine monophosphate-phosphodiesterase type 5. An effective treatment for ED is required to produce an erectile response sufficient for satisfactory sexual performance. This has been documented for sildenafil in men with ED of differing aetiologies and baseline severity in various types of clinical trials. Sildenafil treatment is characterised by a good tolerability profile and low treatment digcontinuation rate caused by treatment-related adverse effects. Most of the adverse effects associated with sildenafil are extensions of the pharmacological action of the drug. There is no significant difference in the adverse effect profile (headache, flushing, dyspepsia, nasal congestion and abnormal vision) of this agent as assessed by clinical data obtained either in the pre- and postlaunch periods. Because of its acceptable risk-benefit ratio, sildenafil can be prescribed to a very large group of patients with ED. The reports of serious cardiovascular events associated with the use of sildenafil (including anecdotal reports of deaths) have been very thoroughly analysed. A number of studies have not shown any difference in the risk of serious cardiovascular events in sildenafil- and placebo-treated patients. However, when making a risk-benefit evaluation, certain subgroups of patients need to be considered separately. In particular, sildenafil is contraindicated in patients receiving nitrate therapy. In some other subgroups of patients, the risks and benefits of treatment need to be assessed on an individual basis and it is hoped that additional data will clarify any possible risks associated with sildenafil administration such patients. It is helpful to compare the risk-benefit profile of sildenafil with the characteristics of other oral drugs for ED. According to the preliminary data, apomorphine and phentolamine are possible future options for the treatment of ED; however, there needs to be further clinical evaluation of these agents. Initial data have shown that sildenafil can be successfully combined with intracavernosal injection in patients nonresponders to either therapy. In conclusion, favourable characteristics make sildenafil suitable for the first-line therapy for a substantial proportion of patients with ED.     

The role of losartan in cost-effective hypertension control

Despite recent guidelines emphasising the need for aggressive treatment in patients with elevated blood pressure, the control of hypertension in Europe and the USA is poor, imposing a considerable burden in terms of patient morbidity and mortality, and associated healthcare costs. A major factor contributing to the suboptimal control of hypertension is the failure of patients to adhere to their prescribed therapy. Drug side-effects are an important cause of non-compliance and prescribing a well-tolerated agent that promotes good compliance is therefore the key to the cost-effective management of hypertension. Several studies have demonstrated that patients are more likely to remain on therapy with the angiotensin II antagonist losartan than other antihypertensives. Although the acquisition costs of new antihypertensives such as losartan are greater than for older drugs, such costs represent only a small proportion of the total cost of prescribing antihypertensive therapy. When accessory costs are also considered, the total cost of care with newer antihypertensives is comparable with those for diuretics. The costs involved if therapy has to be switched due to unacceptable side-effects also need to be taken into account when assessing relative cost effectiveness. Furthermore, savings may accrue from the non-haemodynamic benefits of losartan, such as improved cognitive function and renal protection. Further studies will increase awareness of the true cost effectiveness of antihypertensive drugs.     

Antihypertensive Drugs

For most patients with systemic hypertension, long-term drug treatment is indicated and is beneficial. There is overwhelming evidence to suggest that antihypertensive drugs offer protection against complications of hypertension. Whereas nondrug therapeutic options should be implemented in all patients, a vast majority will require pharmacological treatment to achieve goal blood pressure levels. Fortunately, a number of drugs are available to accomplish successful treatment of hypertensive disorders. While it is conventional to initiate treatment with a single drug, a suitable combination of drugs is often required to control the blood pressure effectively. Although diuretics and β-blockers are effective and well tolerated, other classes of drugs are being increasingly used as the initial choice of therapy for hypertension. Every class of antihypertensive drugs offer advantages and some disadvantage; the physician should weigh the benefits and risks in selecting one drug over another. While the clinical parameters are followed in the management of patients with hypertension, it is also necessary to monitor the patients’ biochemical profile periodically in order to modify and adjust the therapy accordingly. A careful selection of drug therapy along with close follow-up offers the best prospect to reduce the burden of morbidity and mortality in hypertension. This article provides an overview of drugs in the management of patients with hypertension.     

东莞部分社区医生高血压防治知识现状与《中国高血压防治指南））（2009年基层版）差异性分析

目的了解东莞部分社区医生高血压防治知识现状以及与〈〈中国高血压防治指南〉〉（2009年基层版）差异性。方法东莞市部分社区医生现场答卷,以调查高血压相关知识。结果社区医生中,能够掌握心血管病和高血压危险因素的有58％,能够掌握患者高血压其临床评价的有61％,能够掌握患者高血压应用非药物手段进行治疗其内容的有42％,能够掌握关于高血压流行趋势与现状的有38％,能够掌握关于血压水平分类的有38％,能够掌握高血压降压药物其治疗原则的有35％,能够掌握患者高血压其危险分层的有31％,能够掌握降压药物其分类的有30．6％,能够合理的选择患者降压药物的有28％,能够熟悉高血压患者其监测与评估程序的有22％,能够掌握对特殊人群应用降压药物进行治疗的有9％,能够联合应用降压药物对患者进行治疗的有ll％,513％的社区医生知道中国高血压指南,23．8％医生接受过指南相关内容培训。结论社区医生高血压防治知识有待提高,社区高血压治疗需规范和优化。     

Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction

Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothelial function and, erection is a basically vascular event that necessitates an intact endothelium to occur. Hence, ED may be mostly considered as the clinical manifestation of a disease affecting penile circulation as a part of a generalized vascular disorder due to atherosclerosis. Orally active drugs, i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of on-demand drugs licensed for ED treatment and appear to offer advantages over past therapies in terms of ease of administration and cost, and they are now widely advocated as first-line therapy. The recent discovery that chronic not on-demand administration of these drugs may improve erectile and endothelial response in men previously unresponding to on-demand regimes, opens a new scenario in the treatment of men with ED and comorbidities. Finally, the recent approval of PDE5-i sildenafil for the treatment of pulmonary arterial hypertension represents the new challenge for these class of drugs. Aim of this article will be to provide an update on the pathophysiology of ED and how to use of different available PDE5-i in approaching sexual dysfunctional men, pointing out on their characteristic of efficacy and safety and different indications in special sub-populations.     

探讨中国、美国及欧洲高血压防治指南中有关药物治疗的问题

高血压治疗,药物的选择是关键,我国临床应用的降压药物种类,包括中西药及各种复方制剂有几百种之多,但我国高血压的治疗率和控制率都很低,高血压防治形势不容乐观。本文对中国、美国及欧洲高血压防治指南中有关药物治疗方面的差异进行比较,并对高血压药物临床选择的原则进行探讨。中、美、欧指南均认为不同类别的降压药物在某些治疗效果或特殊的人群中确实存在差异,因此对特定的强制性适应症应采用特定类别的降压药物。三个指南都强调合并用药的益处,并建议采用能维持24 h的长效药物或制剂。但三个指南在是否推荐一线治疗药物上存在明显分歧,美国指南建议噻嗪类利尿剂可作为大多数无并发症高血压患者的首选药,而欧洲指南和中国指南均未推荐一线药物,认为几个主要类别的降压药均可用于高血压的起始治疗和维持治疗。中医药是我国特有的宝贵资源,各种降压中成药在临床上有广泛的应用,但由于缺乏高质量证据,2004年中国高血压防治指南中缺少中成药部分。临床上降压药物的选择首先取决于药物的疗效和安全性,在疗效与安全性相差不大的情况下,应优先选择相对价廉的药物。对于我国大多数高血压患者,如果没有必需使用其他药物的适应症,低剂量噻嗪类利尿药可以作为治疗的首选方案。2004年中国高血压防治指南的出台,对我国高血压防治工作具有重要的意义,现阶段应加强指南的推广和实施,促进临床高血压药物的合理使用,提高血压控制率。     

The role of olmesartan medoxomil in the management of hypertension

Intensive blood pressure control is a desirable and obtainable goal in patients with hypertension, according to the most recent treatment guidelines from Europe and the US. Achieving target blood pressure depends on the efficacy of antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non-peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective and well tolerated. Continuation of initial treatment is higher with AT1 receptor antagonists than for any other class of antihypertensive drugs. Olmesartan medoxomil may also have end-organ protective effects that provide additional clinical benefit. Optimal blood pressure control may be achieved faster if initial treatment contains the most efficacious and well tolerated antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment of patients suffering from mild to moderate ESsenTial hypertension), will provide important information on the use of olmesartan medoxomil as an initial treatment for hypertension.     

药物治疗顽固性高血压的研究进展

在高血压患者中,有15％～20％属于顽固性高血压。顽固性高血压具有更高的心血管事件的风险,给患者造成的危害也更严重。临床治疗顽固性高血压,需要结合患者的自身情况,选择不同的降压药联合用药。目前较为常用方案为血管紧张素转换酶抑制剂（或血管紧张素II受体阻滞剂）、钙拮抗剂和噻嗪类利尿剂3种药物组合,或由扩血管药、减慢心率药和利尿剂组合。本文综述了治疗顽固性高血压的联合用药方案和药物选择等方面的研究进展,为更好地治疗该病提供借鉴。     

The Role of Losartan in Cost-effective Hypertension Control

Summary

Despite recent guidelines emphasising the need for aggressive treatment in patients with elevated blood pressure, the control of hypertension in Europe and the USA is poor, imposing a considerable burden in terms of patient morbidity and mortality, and associated healthcare costs. A major factor contributing to the suboptimal control of hypertension is the failure of patients to adhere to their prescribed therapy. Drug side-effects are an important cause of non-compliance and prescribing a well-tolerated agent that promotes good compliance is therefore the key to the cost-effective management of hypertension. Several studies have demonstrated that patients are more likely to remain on therapy with the angiotensin II antagonist losartan than other antihypertensives.

Although the acquisition costs of new antihypertensives such as losartan are greater than for older drugs, such costs represent only a small proportion of the total cost of prescribing antihypertensive therapy. When accessory costs are also considered, the total cost of care with newer antihypertensives is comparable with those for diuretics. The costs involved if therapy has to be switched due to unacceptable side-effects also need to be taken into account when assessing relative cost-effectiveness. Furthermore, savings may accrue from the non-haemodynamic benefits of losartan, such as improved cognitive function and renal protection. Further studies will increase awareness of the true cost-effectiveness of antihypertensive drugs.     

Diabetes, hypertension and erectile dysfunction

Diabetes mellitus (DM) and hypertension are independent risk factors for erectile dysfunction (ED), macrovascular disease and microangiopathy. ED is very common among diabetic patients. Men with DM have ED at an earlier age and with a significantly higher prevalence (as high as 75%). The prevalence of DM also tends to be higher in patients with Peyronie's disease. DM impairs neurogenic and endothelium-mediated relaxation of penile smooth muscle. It is impossible to separate DM from hypertension and from the other vascular risk factors. Good glycaemic and hypertension control in diabetics is very important since these factors increase the risk of both microvascular and macrovascular complications, possibly including ED.     

伐地那非联合表面麻醉剂治疗勃起功能障碍伴早泄的临床研究

目的探讨伐地那非联合表面麻醉剂治疗勃起功能障碍(ED)伴有早泄患者的临床效果和安全性。方法 60例诊断为合并ED的早泄患者,按需每次服用伐地那非20 mg,并将复方利多卡因乳膏于性交前均匀涂搽龟头处,共治疗12周。以阴道内射精潜伏期评价早泄治疗效果,并评估ED的总体疗效和治疗满意度,比较治疗前后的国际勃起功能指数-5(IIEF-5)评分。结果治疗12周后,38例患者报告早泄有好转,有效率达63.3%,平均阴道内射精潜伏时间(IEL-T)由治疗前(0.43±0.31)min延长至(4.2±2.1)min;性交满意度评分由(7.6±2.5)分上升至(10.2±1.9)分,差异均有显著性(P<0.01)。勃起功能改善者共46例,总改善率为76.7%,IIEF-5评分从治疗前的平均11.2(11.2±4.9)分上升到治疗后的平均19.1(19.1±4.1)分,差异有显著性(P<0.01)。不良反应共有8例(13.3%),均为轻度或中度的,未经处理即自行缓解。结论对合并ED的早泄病人,伐地那非联合表面麻醉剂能安全有效地改善其勃起功能,并能显著改善其早泄症状。     

An overview of the diagnosis and treatment of erectile dysfunction

Epidemiological studies have demonstrated an age-stratified increase in the incidence and prevalence of erectile dysfunction (ED). There is a greater degree of openness today when discussing sexual matters and more information on the treatment of ED is available to the public through the media. Quality-of-life issues are now a matter of great importance to the aging population. Men and their partners are no longer prepared to merely accept ED as a natural consequence of aging. The advent of a simple and effective oral therapy for ED has also indirectly fueled the increase in treatment-seeking behaviour among men. Despite great strides in research into ED, our knowledge and understanding of the pathophysiological mechanisms is still in its infancy. As a result, we are able to treat only the symptom of ED rather than prevent it. Common diseases found in the population, such as diabetes mellitus and coronary artery disease appear to be risk factors for the development of ED. Therefore, physicians need to identify any underlying co-existing organic diseases in their patients presenting with ED. Whenever possible, patients are encouraged to attend their consultation sessions with their partners because ED is a condition affecting 'the couple' and not just the man. Psychogenic aspects of ED should also be explored during the consultation. Efforts need to be made to uncover and address the presence of any psychological stressors, if necessary with the help of a psychosexual therapist. The first-line treatment of ED is oral phosphodiesterase-5 inhibitors. For those who do not respond to oral therapy, there is no defined 'step-ladder' escalation in alternative therapy. It is up to the physician to discuss the options with the patient or couple and reach a decision based on their preference.     

Patterns of antihypertensive medication use in hemodialysis patients.

PURPOSE: Patterns of antihypertensive drug use in patients undergoing long-term hemodialysis therapy were studied. METHODS: Patients attending seven outpatient hemodialysis units in Ohio were eligible for the study if they had been receiving the treatment for at least three months. Demographic and clinical data were obtained from patient interviews and computerized databases, and blood pressure (BP) measurements were obtained before dialysis. Labeled names and dosages of antihypertensive drugs were recorded from containers the patients brought with them. Patients were asked to describe their adherence to the medications, their ability to afford the drugs, and their knowledge and beliefs about hypertension. Physical impairments in taking medication were also evaluated. RESULTS: The frequency of hypertension was 89% in the 270 participants. Antihypertensive drugs were prescribed for 76% of the patients; 25% required three or more drugs. Hypertensive patients who were not receiving antihypertensive drugs (14%) had significantly higher BP than patients who were. Calcium-channel blockers were prescribed for 60% of patients, angiotensin-converting-enzyme inhibitors for 33%, and beta-blockers for 34%. Eighty-three percent said the cost of drugs was never a problem, and 23% said they sometimes forgot to take their medication. Almost all patients said they would not stop taking antihypertensive drugs if they were feeling better and agreed that monitoring BP was important. Twenty-two percent could not read the warning on a standard tablet container, and 12% could not remove one tablet from the container. CONCLUSION: Multidrug antihypertensive therapy was common among hemodialysis patients and was associated with significantly lower BP; calcium-channel blockers were the most frequently prescribed agents. Most patients said they could afford drugs and reported good adherence to antihypertensive drug therapy.     

Treatment of erectile dysfunction in patients with cardiovascular disease : guide to drug selection

Erectile dysfunction (ED) is common in cardiac patients and shares the same risk factors--smoking, hypertension, hyperlipidaemia and diabetes mellitus. Sexual activity is not unduly stressful to the heart and, providing patients are properly assessed using established guidelines, sexual intercourse can be enjoyed without increased risk. The treatment of ED in patients with cardiovascular disease has been transformed by the introduction of the oral phosphodiesterase type 5 inhibitors, the first of which was sildenafil. Success in restoring erectile function is possible in up to 80% of patients (depending on the aetiology) with minimal adverse effects. A synergistic hypotensive effect with nitrates, and almost certainly nicorandil, is the only major contraindication. ED in asymptomatic patients may be a marker of silent vascular disease or increased vascular risk factors and should alert the physician to the need for cardiac risk screening. ED is common in patients with cardiovascular disease and should be routinely enquired about. ED is a distressing condition for the man and his partner, and severely impairs quality of life. Patients with cardiovascular disease and patients with diabetes represent the largest group of patients with ED, the majority of whom benefit from the drug therapies currently available. Addressing ED in patients with cardiovascular disease can lead to a substantial improvement in quality of life and success is not difficult to achieve.