sildenafil-citrate and Headache

The number of studies associating the use of sildenafil in gestation is increasing. This drug inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. For this reason, promising results have been observed related to the prevention of preeclampsia and intrauterine growth restriction and to improvement of maternal-fetal morbidity in cases of placental insufficiency.. To evaluate the benefits of using sildenafil in pregnancy.. MEDLINE, ClinicalTrials.gov, Embase, LILACS and Cochrane databases were searched through September 2018. There was no restriction in language or year of publication. This study was registered in PROSPERO (CRD42017060288).. Randomized clinical trials which used sildenafil for treatment or prevention of obstetric diseases compared with placebo were selected.. The results were obtained using the inverse variance method for continuous variables and Man-Whitney for categorical variables.. Among a population of 598 pregnant women from the seven clinical trials included, 139 had pre-eclampsia, 275 had intrauterine growth restriction, and 184 had oligohydramnios. A significant increase of 222.58 grams [27.75 to 417.41] was observed in the fetal weight at birth of patients taking sildenafil. The other outcomes did not show any statistical significance. This may be due to the small number of patients used in each study and the great heterogeneity between the groups.. Sildenafil could be associated with increasing fetal weight at birth in placental insufficiency despite the limitations of this meta-analysis, even though more studies in this field are needed to introduce this drug into obstetric clinical practice.

Topics: Birth Weight; Delivery, Obstetric; Female; Fetus; Gestational Age; Headache; Humans; Infant; Infant Mortality; Labor, Obstetric; Pregnancy; Pregnancy Outcome; Publication Bias; Risk; Sildenafil Citrate; Umbilical Arteries

This systematic review evaluates maternal tolerance and obstetric and perinatal outcomes following sildenafil citrate (SC) use in human pregnancy.. Scopus, PubMed, Cochrane Library, Web of Science, Embase, and Google Scholar were searched. Relevant full-text studies including case series and reports in English were included. Publications were excluded if the pregnancy was terminated or if SC was used only at conception.. Sixteen studies were included (n = 165). Indications for use and outcomes were variably reported. Maternal outcomes reported were headache (45.8%, 49/107), visual disturbances (17.3%, 14/81), dyspepsia/epigastric pain (15.8%, 15/95), and hypotension (0%, 0/39). There were more caesarean (83.3%, 55/66) than vaginal deliveries (16.7%, 11/66) and postpartum haemorrhage occurred in 3.9% (3/76) of women exposed to SC. Neonatal outcomes including nursery admission (67.3%, 35/52), Apgar scores <7 at 5 min (7.1%, 4/56), and cord arterial pH <7.1 (0%, 0/17) were reported. Stillbirths (4.3%, 3/69) and neonatal deaths (3.9%, 5/129) were comparable to SC-naïve groups. There were no congenital malformations (0%, 0/35).. Despite limited data, overall there does not appear to be any severe adverse maternal side effects nor any increase in the rate of stillbirths, neonatal deaths, or congenital anomalies attributed to SC.

Topics: Delivery, Obstetric; Female; Headache; Humans; Infant, Newborn; Pain; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Sildenafil Citrate; Vision Disorders

Clinical studies evaluating the effectiveness and safety of phosphodiesterase type 5 inhibitors (PDE5is) for female sexual dysfunction have reported conflicting results.. To systematically review evidence from studies comparing PDE5is with placebo in the treatment of female sexual dysfunction.. Searches of PubMed, the Cochrane Library, and Embase databases were performed using the MeSH terms "females/female/women", "sexual", and "sildenafil/tadalafil/vardenafil/PDE5/PDE5i".. All randomized controlled trials, available in English, published no later than January 28, 2015 comparing the effectiveness of PDE5is, or PDE5is in combination with other agents, with placebo in improving female sexual function were included.. The inclusion criteria were met by 14 studies, which were analyzed by two reviewers.. The randomized controlled trials included in the present study adopted different questionnaires for measuring sexual function; consequently, most of the data had to be considered separately rather than pooled. Generally, the use of PDE5is resulted in significant improvements in sexual function compared with placebo, with some studies demonstrating negative results. Pooled data regarding adverse events demonstrated significantly higher rates of headache, flushing, and changes in vision in PDE5i-treated patients.. PDE5is could be an effective treatment modality for female sexual dysfunction. Although there were significant increases in adverse events in comparison with placebo, PDE5is were still relatively safe.

Topics: Female; Flushing; Headache; Humans; Nausea; Orgasm; Phosphodiesterase 5 Inhibitors; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Sildenafil Citrate; Treatment Outcome; Vision Disorders

Topics: Animals; Erectile Dysfunction; Headache; Humans; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache. Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human experimentation make it highly likely that antagonizing NO effects will be effective in the treatment of primary headaches. Nonselective NOS inhibitors are likely to have side effects whereas selective compounds are now in early clinical trials. Antagonizing the rate limiting cofactor tetrahydrobiopterin seems another very likely new treatment. It is more unlikely that antagonism of cGMP or its formation will be feasible, but augmenting its breakdown via phosphodiesterase activation is a possibility, as well as other ways of inhibiting the NO-cGMP pathway.

Topics: Cyclic GMP; Headache; Humans; Nitric Oxide; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones

To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction.. The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer.. Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes.. Two reviewers independently evaluated study quality and extracted data in a standardized fashion.. Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death.. Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.

Topics: Age Factors; Aged; Dose-Response Relationship, Drug; Dyspepsia; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents; Vision Disorders

Since the sexual revolution of the 1960s, medical complications of sexual activity and sexual side effects related to use of medications have become a significant part of healthcare practice. Specifically, there has been an expanding interest in the treatment of headaches and their relationship to sexual function. Most sexual side effects associated with headache treatment are benign and can be managed with reassurance or changes in medication regimens. However, sudden headache should always be investigated carefully to rule out a dangerous intracranial event.

Topics: Antidepressive Agents; Antihypertensive Agents; Coitus; Female; Headache; HIV Infections; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones

It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura.. In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura.. Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher's exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher's exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks.. Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase.

Topics: Cross-Over Studies; Double-Blind Method; Epilepsy; Headache; Humans; Migraine Disorders; Migraine with Aura; Sildenafil Citrate

Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery.. In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days.. Twelve healthy volunteers completed the study. The area under the curve. An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels. We suggest that intradural artery dilation is associated with headache induced by calcitonin gene-related peptide and sildenafil.

Topics: Adult; Calcitonin Gene-Related Peptide; Cross-Over Studies; Double-Blind Method; Female; Headache; Healthy Volunteers; Humans; Magnetic Resonance Angiography; Male; Meningeal Arteries; Sildenafil Citrate; Vasodilation; Vasodilator Agents; Young Adult

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

Topics: Acute Disease; Adult; Altitude; Altitude Sickness; Antioxidants; Bolivia; Expeditions; Fatigue; Female; Headache; Humans; Male; Mountaineering; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sleep Wake Disorders; Sulfones; Surveys and Questionnaires; Syndrome; Tanzania; Vasodilator Agents; Visual Analog Scale; Young Adult

Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy.. A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH.. Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 ± 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double-blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]).. Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Antihypertensive Agents; Blood Pressure; Bosentan; Double-Blind Method; Drug Therapy, Combination; Epoprostenol; Female; Headache; Humans; Hypertension, Pulmonary; Incidence; Longitudinal Studies; Male; Middle Aged; Nausea; Physical Endurance; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Young Adult

Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70.3+/-6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.

Topics: Adult; Cerebrovascular Circulation; Evoked Potentials, Visual; Female; Headache; Hemodynamics; Humans; Hypercapnia; Magnetic Resonance Imaging; Photic Stimulation; Piperazines; Purines; Sildenafil Citrate; Sulfones; Young Adult

The pharmacokinetic interaction between sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, and ambrisentan, an ET(A)-selective, propanoic acid-based endothelin receptor antagonist (ERA), was studied in a 2-period crossover study in 19 healthy volunteers, with ambrisentan exposure (AUC(0-infinity)) and maximum plasma concentration (C(max)) determined over 24 hours for a 10-mg dose of ambrisentan alone and again after 7 days of sildenafil 20 mg 3 times daily. The AUC(0-infinity) and C(max) for sildenafil and N-desmethyl sildenafil (active metabolite) were determined over 24 hours for a 20-mg dose of sildenafil alone and again after 7 days of dosing with ambrisentan 10 mg once daily. There was no clinically relevant pharmacokinetic interaction between ambrisentan and sildenafil or N-desmethyl sildenafil. Ambrisentan C(max) was unchanged (96.3% [90% confidence interval: 86.0%-107.8%]), with a minor increase in AUC(0-infinity) (108.5% [102.6%-111.7%]) with sildenafil coadministration. Sildenafil C(max) was increased slightly (113.4% [99.6%-129.1%]), and AUC(0-infinity) was unchanged (98.7% [91.2%-110.5%]) with ambrisentan coadministration. N-desmethyl sildenafil was unaltered. Dose adjustment of either drug is not necessary compared with administration alone.

Topics: Administration, Oral; Adolescent; Adult; Analysis of Variance; Area Under Curve; Chromatography, High Pressure Liquid; Cross-Over Studies; Drug Interactions; Endothelin A Receptor Antagonists; Female; Follow-Up Studies; Half-Life; Headache; Humans; Male; Middle Aged; Pain; Phenylpropionates; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Pyridazines; Sildenafil Citrate; Sulfones; Tandem Mass Spectrometry; Young Adult

Oral sildenafil and intravenous epoprostenol have independently been shown to be effective in patients with pulmonary arterial hypertension.. To investigate the effect of adding oral sildenafil to long-term intravenous epoprostenol in patients with pulmonary arterial hypertension.. A 16-week, double-blind, placebo-controlled, parallel-group study.. Multinational study at 41 centers in 11 countries from 3 July 2003 to 27 January 2006.. 267 patients with pulmonary arterial hypertension (idiopathic, associated anorexigen use or connective tissue disease, or corrected congenital heart disease) who were receiving long-term intravenous epoprostenol therapy.. Patients were randomly assigned to receive placebo or sildenafil, 20 mg three times daily, titrated to 40 mg and 80 mg three times daily, as tolerated, at 4-week intervals. Of 265 patients who received treatment, 256 (97%) patients (123 in the placebo group and 133 in the sildenafil group) completed the study.. Change from baseline in exercise capacity measured by 6-minute walk distance (primary end point) and hemodynamic measurements, time to clinical worsening, and Borg dyspnea score (secondary end points).. A placebo-adjusted increase of 28.8 meters (95% CI, 13.9 to 43.8 meters) in the 6-minute walk distance occurred in patients in the sildenafil group; these improvements were most prominent among patients with baseline distances of 325 meters or more. Relative to epoprostenol monotherapy, addition of sildenafil resulted in a greater change in mean pulmonary arterial pressure by -3.8 mm Hg (CI, -5.6 to -2.1 mm Hg); cardiac output by 0.9 L/min (CI, 0.5 to 1.2 L/min); and longer time to clinical worsening, with a smaller proportion of patients experiencing a worsening event in the sildenafil group (0.062) than in the placebo group (0.195) by week 16 (P = 0.002). Health-related quality of life also improved in patients who received combined therapy compared with those who received epoprostenol monotherapy. There was no effect on the Borg dyspnea score. Of the side effects generally associated with sildenafil treatment, the most commonly reported in the placebo and sildenafil groups, respectively, were headache (34% and 57%; difference, 23 percentage points [CI, 12 to 35 percentage points]), dyspepsia (2% and 16%; difference, 13 percentage points [CI, 7 to 20 percentage points]), pain in extremity (18% and 25%; difference, 8 percentage points [CI, -2 to 18 percentage points]), and nausea (18% and 25%; difference, 8 percentage points [CI, -2 to 18 percentage points]).. The study excluded patients with pulmonary arterial hypertension associated with other causes. There was an imbalance in missing data between groups, with 8 placebo recipients having no postbaseline walk assessment compared with 1 sildenafil recipient. These patients were excluded from the analysis.. In some patients with pulmonary arterial hypertension, the addition of sildenafil to long-term intravenous epoprostenol therapy improves exercise capacity, hemodynamic measurements, time to clinical worsening, and quality of life, but not Borg dyspnea score. Increased rates of headache and dyspepsia occurred with the addition of sildenafil.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antihypertensive Agents; Double-Blind Method; Drug Therapy, Combination; Dyspepsia; Epoprostenol; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Injections, Intravenous; Male; Middle Aged; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents; Walking

The aim of this study was to establish the prevalence of erectile dysfunction (ED) in hypertensive patients in specialized care hypertension units (SCHUs) and to assess the effectiveness and tolerability of sildenafil treatment.. This was a multicenter, prospective, open, observational pharmacoepidemiology study conducted in 25 Spanish SCHUs. A total of 2130 men with essential hypertension under treatment were recruited. In a second phase, 291 subjects with a score < or = 21 in the Sexual Health Inventory for Men (SHIM) received sildenafil (50 mg/day) as required 30 to 60 minutes before sexual activity, and were evaluated by the International Index of Erectile Function (IIEF).. A total of 975 subjects (45.8%) had a score < or = 21 in the SHIM. In the second phase, sildenafil improved the score in the erectile function domain in 232 patients (83.2%). Severity of ED significantly improved (P <.001); severe (22.3% to 7.7%), moderate (23% to 5.6%), and mild impairment (36.3% to 44.8%). The IIEF was normalized in 39.1% of patients who completed post-treatment IIEF. In all, 33 subjects (11.8%) failed to complete the study: two (0.7%) because of lack of efficacy, two (0.7%) intercurrent disease, 10 (3.6%) failure to return to the visits, three (1.1%) fear of therapy, four (1.4%) adverse effects requiring treatment discontinuation, and 12 (4.3%) protocol violations. No statistically significant association was found between the prevalence of adverse effects and antihypertensive treatment with single drug or combination therapy.. A high incidence of ED was found in hypertensive patients from Spanish SCHUs. Sildenafil showed an excellent response and safety profile.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Antihypertensive Agents; Body Mass Index; Erectile Dysfunction; Headache; Humans; Hypertension; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following subcutaneous administration to healthy male subjects and to patients with erectile dysfunction (ED) who report an inadequate response to Viagra. An inadequate response was defined for this study by patient report indicating that achievement of an erection suitable for vaginal penetration occurred < or =50% of the time while taking 100 mg Viagra. Erectile responses were assessed by RigiScan in healthy subjects in the absence of visual sexual stimulation (VSS) and in ED patients in the presence of VSS. Doses ranging from 0.3 to 10 mg were administered to healthy male subjects, resulting in a statistically significant erectile response at doses greater than 1.0 mg. ED patients were treated with placebo, 4 or 6 mg PT-141 in a crossover design in the presence of VSS. The erectile response induced by PT-141 was statistically significant at both doses. PT-141 was safe and well tolerated in both studies. The erectogenic potential of PT-141, its tolerability profile and its ability to cause significant erections in patients who do not have an adequate response to a PDE5 inhibitor suggest that PT-141 may provide an alternative treatment for ED with a potentially broad patient base.

Topics: Adult; alpha-MSH; Cross-Over Studies; Dose-Response Relationship, Drug; Erectile Dysfunction; Headache; Humans; Injections, Subcutaneous; Male; Middle Aged; Nausea; Penile Erection; Peptides, Cyclic; Piperazines; Purines; Receptors, Melanocortin; Reference Values; Sildenafil Citrate; Sulfones; Time Factors; Vomiting

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce headache and migraine, no significant differences in plasma levels of CGRP, cGMP and cAMP were detected after sildenafil compared with placebo. In conclusion, plasma levels of CGRP, cGMP and cAMP remain normal during sildenafil-induced headache or migraine. However, since previous studies indicate an important role of these signalling molecules, the present study questions whether cAMP and cGMP in peripheral blood can be used for monitoring pathophysiological events in headache and migraine mechanisms.

Topics: Adult; Analysis of Variance; Calcitonin Gene-Related Peptide; Cross-Over Studies; Cyclic AMP; Cyclic GMP; Double-Blind Method; Female; Headache; Humans; Male; Migraine without Aura; Piperazines; Purines; Sildenafil Citrate; Sulfones

The aim of the present study was to show the efficacy and safety of sublingual sildenafil and to determine whether lower doses cause the same effect with a faster onset of action in this mode of application.. Forty consecutive patients with erectile dysfunction for more than three months were included in the study. The mean age was 55 years (range, 25-65). Serum glucose and testosterone levels, lipid profile and erectile function scores were obtained in all patients. Twenty patients received placebos and the other 20 patients received 20 mg sublingual sildenafil in a double blind randomized design.. The effect of sildenafil on erection was significantly higher than that of placebo. Sixty-five percent of patients (13/20) who received sublingual sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in the placebo group (3/20). The mean onset of action with sublingual sildenafil was 15.5 min and lasted for an average of 40 min. Minimal headaches, sweating and flushing were noted as the side-effects.. 20 mg sublingual sildenafil is safe and effective in the treatment of erectile dysfunction. Sublingual administration has some advantages as it is not effected by food ingestion and quickly appears in the circulation. These advantages provide a faster onset of action with a lower dose when compared to oral sildenafil. Sublingual use of sildenafil may be more cost-effective and possibly provides a more predictable onset of action.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Sublingual; Adult; Aged; Dose-Response Relationship, Drug; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Sweating; Treatment Outcome

Viagra (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity.. We investigated the duration of action of sildenafil in men with ED.. This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36-68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of >or= 60% rigidity, assessed by penile plethysmography (RigiScan), and the proportion of sildenafil responders, defined as patients with erections of >or= 60% rigidity for >or= 4 minutes and >or= 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded.. At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with >or= 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P < 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration.. Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.

Topics: Adult; Aged; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Plethysmography; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome

Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBF(mca)) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P = 0.01). V(mca) (P = 0.1) and rCBF(mca) (P = 0.93) remained unchanged after sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62 +/- 2 to 74 +/- 3 beats/min (P = 0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Blood Flow Velocity; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Female; Headache; Heart Rate; Humans; Male; Middle Cerebral Artery; Migraine Disorders; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Radial Artery; Sildenafil Citrate; Sulfones; Temporal Arteries; Tomography, Emission-Computed, Single-Photon; Ultrasonography, Doppler

To assess the long-term sexual potency and attrition in sexual function after iodine-125 ((125)I) seed radiotherapy and the effect of sildenafil on radiation-induced erectile dysfunction (ED).. This prospective study consisted of 86 sexually active patients (mean age 63.5 +/- 7.7 years) who underwent (125)I seed implantation from 1997 to 1999 to treat low-volume prostate cancer (prostate-specific antigen less than 10 ng/mL, Gleason score 6 or less, stage T1-T2). All patients were followed up every 6 to 8 months for 4 years. Patients prescribed sildenafil citrate for ED completed the abridged five-item version of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires.. The median follow-up was 49.7 months (range 36 to 66). Of 86 patients, 43 (50%) did not initiate drug therapy; and only 36 (83.7%) of the 43 were interviewed at 4 years. Twenty-three (63.8%) of the 36 patients had erections sufficient for vaginal penetration, with a total mean +/- SD IIEF-5 score of 15.76 +/- 1.13. The other 50% (43 of 86) initiated sildenafil citrate for treatment of ED after seed implantation, with a minimal follow-up of 6 months. At 4 years, 32 (74%) of the 43 were responding positively to sildenafil citrate, with a total IIEF-5 score of 18.3 +/- 1.2. The mean EDITS +/- SD score was 76.5 +/- 3.2, and the spousal satisfaction rate was 72% (31 of 43). The dropout rate was 37% (16 of 43); 10 (63%) of the 16 discontinued because of a lack of efficacy, 3 (19%) because of a return of natural erections sufficient for vaginal penetration, and 3 (19%) discontinued because of side effects (headaches).. ED is a major long-term issue after (125)I seed radiotherapy, with a long-term potency rate of 29%. Sildenafil citrate improves erections in most patients after (125)I seed implantation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Brachytherapy; Erectile Dysfunction; Follow-Up Studies; Headache; Humans; Iodine Radioisotopes; Male; Middle Aged; Patient Satisfaction; Piperazines; Prospective Studies; Prostatic Neoplasms; Purines; Severity of Illness Index; Sexual Partners; Sildenafil Citrate; Sulfones; Vasodilator Agents

Sildenafil citrate (Viagra Pfizer, New York, NY) is indicated for the treatment of erectile dysfunction in men. The nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) involved in penile erection and enhanced by sildenafil may also play a role in some components of the female sexual arousal response. The efficacy and safety of sildenafil were evaluated in estrogenized and estrogen-deficient women with sexual dysfunction that included female sexual arousal disorder (FSAD).. Patients were randomized to receive 10-100 mg sildenafil or matching placebo. To assess efficacy, patients completed two global efficacy questions (GEQ), the Life Satisfaction Checklist (LSC), an event log of sexual activity, and a 31-item sexual function questionnaire (SFQ). To assess safety, adverse event (AE) data were recorded.. A total of 577 estrogenized and 204 estrogen-deficient women were randomized to treatment. All were diagnosed with FSAD, but it was the primary presenting symptom in only 46% and 50% of women, respectively. Differences in efficacy between sildenafil and placebo were not significant for any patient or partner end points (e.g., the two GEQ, the sexual event logs, the LSC, and the SFQ). The main AE were headache, flushing, rhinitis, nausea, visual disturbances, and dyspepsia, which were generally mild to moderate in nature.. Any genital physiological effect of sildenafil was not perceived as improving the sexual response in estrogenized or estrogen-deficient women with a broad spectrum of sexual dysfunction that included FSAD. Whether more specific subgroups of women with FSAD could potentially benefit from treatment with sildenafil is an area for future research.

Topics: Adult; Analysis of Variance; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Estradiol; Estrogen Replacement Therapy; Female; Flushing; Headache; Humans; Middle Aged; Nausea; Piperazines; Purines; Rhinitis; Sexual Behavior; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Statistics as Topic; Sulfones; Surveys and Questionnaires; Treatment Outcome; Vasodilator Agents; Vision Disorders

Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler, and regional cerebral blood flow in the perfusion area of the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and xenon inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasound. Blood pressure and heart rate were recorded repeatedly. Headache responses and tenderness of pericranial muscles were scored verbally. Sildenafil caused no significant changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart rate increased and diastolic blood pressure decreased significantly compared to placebo. Despite the lack of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Brain; Cerebral Arteries; Cerebrovascular Circulation; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Female; Headache; Hemodynamics; Humans; Male; Muscle, Skeletal; Pain; Papaverine; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Reference Values; Sildenafil Citrate; Sulfones; Time Factors; Ultrasonography, Doppler, Transcranial; Vasodilator Agents

The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.. We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001).. A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.

Topics: Administration, Oral; Adult; Cyclic GMP; Diuretics; Drug Therapy, Combination; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Predictive Value of Tests; Pulmonary Artery; Pulmonary Circulation; Pulmonary Wedge Pressure; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Warfarin

The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors.. The short-term effects of 8.4 to 10.5 microgram of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4+/-1.3 versus 6.4+/-1.1 mm Hg; P<0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8+/-1.4 versus 9.4+/-1.3 mm Hg; P<0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects.. Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.

Topics: Administration, Inhalation; Administration, Oral; Blood Pressure; Cardiac Output; Cough; Drug Therapy, Combination; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nausea; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents

We evaluated the safety and side effects of sildenafil in a group of sexually active volunteers younger than 40 years under conditions without sexual stimulation. Single oral dose of 50 mg dildenafil (n = 20) or placebo (n = 20) was randomly administered to 40 sexually active volunteers with the mean age of 26.80 +/- 5.29 in sildenafil group and 25.70 +/- 4.95 in placebo group. All the subjects were informed about the study, but not about the medicine. The following tests were performed immediately before and 90 minutes after the administration of the medicine: resting heart rate, blood pressure, electrocardiogram, visual acuity, color vision. The subjects were also asked to describe any discomfort or difference. Mann Whitney U test was used for statistical analyses. The only statistically significant difference was between heart rates before and after the administration of the sildenafil (p = 0.02). Color vision, visual acuity tests yielded no differences. The decrease in blood pressure was not significant. The most common side effects were flushing (75% and 0%), headache (50% and 5%), dyspepsia (15% and 5%), unintentional incomplete sexual arousal (15% and 0%) and palpitation (15% and 10%) in groups of sildenafil and placebo, respectively. The only serious side effect requiring medical treatment was arthralgia on the knee in one subject. Although these side effects can be acceptable, the likelihood of these side effects needs to be made clear to potential users of this medication.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Arthralgia; Blood Pressure; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Heart Rate; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

To evaluate the effectiveness of sildenafil (Viagra) in the treatment of male erectile dysfunction in Nairobi.. Prospective open label extension study.. Urology clinics at the Nairobi Hospital, Kenyatta National Hospital and the author's private clinic in Hurlingham, Nairobi.. Two hundred and nineteen adult male patients with erectile dysfunction.. The age range was 33-80 years with a mean of 62.5 years and a peak incidence in the 60-69 year age group. One hundred and nineteen patients (54.34%) had organic causes, 85 patients (38.81%) had psychogenic causes and 15 patients had mixed causes. Two hundred patients (91.32%) had improved sexual function after treatment with viagra. This improvement was sustained during the study period of sixteen weeks and included improved erectile and orgasmic functions and overall sexual satisfaction. One hundred and fifty seven of these patients responded to therapy with 50 mg of viagra; 40 patients with 25 mg and three patients with 100 mg of therapy. Nineteen patients (8.68%) had no improvement in sexual function after viagra administration. Seven patients (3.2%) had adverse effects which were mild and transient. They included mild headaches in three patients, mild dyspepsia in two patients and facial flushing and nausea and vomiting in one patient, respectively.. Oral sildenafil (Viagra) is an effective well tolerated and simple treatment for male erectile dysfunction in the majority of cases. The cost of treatment at about ten United States dollars for the 50 mg tablet is prohibitive and may limit its wide use by many deserving patients in this locality.. This prospective open-label extension study was carried out to evaluate the effectiveness of sildenafil (Viagra) in the treatment of male erectile dysfunction in Nairobi, Kenya. A total of 219 adult male patients with erectile dysfunction were instructed to take 50 mg, 25 mg, or 100 mg of sildenafil orally 1 hour prior to planned sexual activity, but not more than once every 24 hours. Patients were reviewed at 4-week intervals for 16 weeks to assess the efficacy and adverse effects of the drug. The age range was 33-80 years with a mean of 62.5 years and a peak incidence in the 60-69 year age group. The causes of erectile dysfunction were organic (n = 119, 54.34%), psychogenic (n = 85, 38.81%), and mixed (n = 15). 200 patients (91.32%) had improved sexual function after treatment with Viagra. This improvement included improved erectile and orgasmic functions and overall sexual satisfaction. 157 patients responded to the 50-mg treatment regimen; 40, to the 25-mg regimen; and 3, to the 100-mg regimen. No improvement in sexual function was reported in 19 patients (8.68%) after Viagra administration. In addition, 7 patients reported mild and transient adverse effects of the drug, including mild headache, dyspepsia, facial flushing, nausea, and vomiting. In conclusion, oral sildenafil (Viagra) is an effective well-tolerated and simple treatment for male erectile dysfunction in the majority of cases. However, the cost of treatment may prohibit and limit its wide use by many deserving patients in this area.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Aged, 80 and over; Drug Costs; Dyspepsia; Erectile Dysfunction; Headache; Humans; Kenya; Male; Middle Aged; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Urban Health

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Double-Blind Method; Dyspepsia; Enzyme Inhibitors; Erectile Dysfunction; Flushing; Headache; Humans; Middle Aged; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones

Topics: Brain; Brain Ischemia; Carbolines; Coitus; Headache; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Paresis; Piperazines; Purines; Recurrence; Sildenafil Citrate; Smoking; Stroke; Sulfones; Tadalafil; Vasodilator Agents

Topics: Administration, Oral; Adolescent; Adult; Aged; Antihypertensive Agents; Double-Blind Method; Drug Therapy, Combination; Dyspepsia; Epoprostenol; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Injections, Intravenous; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents; Walking

Topics: Adult; Aged; Aged, 80 and over; Erectile Dysfunction; Headache; Hot Flashes; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice.. A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects.. The adverse reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects.. The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.

Topics: Adult; Aged; Dizziness; Dyspepsia; Erectile Dysfunction; Flushing; Headache; Humans; Incidence; Male; Middle Aged; Nose; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Vision, Ocular