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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors investigated the optima dose (efficacy and safety) of moxisylyte, an alpha-blocking agent, in a double-blind placebo-controlled crossover study in 30 patients. The origin of the erectile dysfunction was predominantly psychological in 14 patients and neurological in 16 patients. Each patient received 4 intracavernous injections in a randomized order (placebo, 10, 20, 30 mg of moxisylyte) at 7-day intervals. Regardless of the dose, moxisylyte induced significantly greater penile responses than placebo on all erection criteria. The frequency of responses allowing sexual intercourse appeared to be dose-dependent in the two aetiological groups. The erectile responses most frequently obtained were complete rigidity in the "neurological" group and tumescence in the "psychological" group. The safety was excellent for 95.6% of injections and no case of priapism was observed. One patient (neurological patient) experienced two prolonged erections after the dose of 20 mg and another patient (psychological patient) reported 2 headaches after the dose of 30 mg. No pain was experienced on injection. Moxisylyte is very well tolerated and is able to induce an erectile response from the dose of 10 mg. This dose appears to be sufficient in patients with central neurological erectile dysfunction; a dose of 20 mg tends to improve the quality of response in patients with a predominantly psychological disorder, although the differences observed between the doses were not statistically significant in this number limited of patients.
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PMID:[Effectiveness of and tolerance to intracavernous injection of moxisylyte in patients with erectile dysfunction: effect/dose relationship versus placebo]. 858 Sep 80

This study was done to evaluate the effectiveness of transdermal nitroglycerin in the treatment of erectile dysfunction in males with spinal cord lesions as compared to the treatment with intracavernous injection of papaverine. The study design used was an open, randomized, cross over trial of intracavernous injection papaverine versus transdermal nitroglycerin. Twenty eight male patients with spinal cord lesions with erectile dysfunction were included in the study, and were subjected to intracavernous injection of papaverine and transdermal nitroglycerin with an interval of 2 weeks as the wash out period. Objectively, the times taken for the onset and the duration of erection were noted. The length of the penis and its circumference at its base were measured at intervals until the erection subsided. The volume of the penis at the onset and at the peak of erection was calculated. Twenty six patients (ie 93%) who received an injection of papaverine, and 17 (ie 61%) of the patients who received nitroglycerin showed a complete response. The difference was statistically significant (P = 0.004). Nine (32%) patients had complications with the injection of papaverine. The only complication noted with the application of a nitroglycerin patch was mild headache, experienced by six (21%) patients. It was concluded from the study that intracavernous injection of papaverine is more effective than transdermal nitroglycerin in the treatment of erectile dysfunction in patients with spinal cord lesions.
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PMID:Comparison of transdermal nitroglycerin and intracavernous injection of papaverine in the treatment of erectile dysfunction in patients with spinal cord lesions. 904 17

Therapeutic equivalence should be demonstrated in a randomised, reference-controlled multicentric double blind clinical trial with PRO 160/120, a combination of Sabal- and Urtica-Extract, and Finasteride, respectively, in patients suffering from benign prostatic hyperplasia (BPH, Stage I to II according to Aiken). The study involved 543 patients, who were treated for 48 weeks with two capsules of PRO 160/120 or one capsule of Finasteride per day, in a double dummy design. Primary variable was the change of the maximum urinary flow after 24 weeks of therapy in comparison to therapy start. As secondary variables urodynamic parameters such as average urinary flow, miction volume and miction time were monitored. Urinary symptoms were recorded by the International-Prostate-Symptom-Score (I-PSS, Paris 1993). Additionally, the impacts of the symptoms on quality of life had been assessed by a quality of life questionnaire according to The American Urological Association Measurement Committee (1991). An increase of the urinary flow rate could be observed in both treatment groups (1.9 ml/s with PRO 160/ 120; 2.4 ml/s with Finasteride). During the trial, the average urinary flow increased, whereas the miction time decreased in both groups in a similar extent. The miction volume did not show any relevant differences after treatment with either PRO 160/120 or Finasteride. The I-PSS decreased from 11.3 at the therapy start to 8.2 after 24 weeks and 6.5 (week 48) under PRO 160/120 and from 11.8 to 8.0 and 6.2, under Finasteride, respectively. Accordingly, life quality improved between therapy start and therapy end from 7.5 to 4.3 with PRO 160/120 and from 7.7 to 4.1 with Finasteride. In terms of safety aspects less adverse events occurred with the Sabal/Urtica-Extract as with Finasteride. Especially less cases of diminished ejaculation volume, erectile dysfunction and headache have been reported.
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PMID:[Combination of Sabal and Urtica extract vs. finasteride in benign prostatic hyperplasia (Aiken stages I to II). Comparison of therapeutic effectiveness in a one year double-blind study]. 954 Jan 90

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.
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PMID:Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. 964 40

Erectile dysfunction may have psychological as well as a variety of organic causes. This necessitates in each case a careful medical evaluation. Various commonly used drugs, as well as alcohol and narcotics, may interfere with erection and should, whenever possible, be discontinued before starting treatment. Organic diseases should be identified and, if feasible, specially treated. In the remaining majority of afflicted men, psychological treatment and partner counseling may produce an improvement, but ultimately what is necessary remains an effective and safe medication. The drug, Sildenafil, introduces a new therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is released from nerves into the cells of the penile erectile bodies. NO activates in turn its "second messenger", the substance cyclic GMP, and the latter induces the vasorelaxation and blood filling of the erectile bodies. Orally administered Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men with erectile dysfunction the NO-stimulated cyclic GMP concentration and, thereby, improves erection. This new therapy is attractive because 1. Sildenafil is the first pill (for oral use) with established efficacy that benefits most men with insufficient erection; 2. compared with previous therapeutic approaches (such as drug injections in the penis, instillations into the urinary duct, vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to take and appears well tolerated with no risk of a prolonged erection; 3. remarkably, this medication stimulates erection only during sexual arousal and, thus, has a rather "natural" effect, and 4. side effects (including headache, facial flushing and dyspepsia or epigastric discomfort) were mostly of mild degree and transient, so that only 4% of men interrupted treatment for this reason. Sildenafil does not need to be taken daily, but may be taken, when needed, 1 hour before a planned sexual activity. The new pill has the potential to enliven the boys "wunder horn" with fresh sound.
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PMID:[New principle in therapy of erectile dysfunction: sildenafil]. 965 82

The efficacy and safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in men with diabetes mellitus and erectile dysfunction (ED). Twenty-one men (aged 42-65 years) were enrolled in a double-blind, placebo-controlled, three-way crossover study conducted in two parts. In part I, the effect of a single dose (25 mg or 50 mg) of sildenafil or placebo on penile rigidity was assessed by penile plethysmography during visual sexual stimulation. In part II, daily diary records of erectile activity and a global efficacy question were used to evaluate once-daily dosing with 25 mg or 50 mg of sildenafil or placebo for 10 days. After a single 50 mg dose of sildenafil, the adjusted geometric mean duration (min) of penile rigidity >60% at the base of the penis during visual sexual stimulation was significantly increased (10.1 min) compared with placebo (2.8 min; p = 0.0053). In part II, sildenafil significantly increased the number of erections considered sufficiently hard for vaginal penetration compared with placebo (p = 0.0005). Improved erections were reported by 50% and 52% of patients treated with 25 mg and 50 mg of sildenafil, respectively, compared with 10% of those receiving placebo (p values < 0.05). Adverse events were mostly mild or moderate in nature and included muscular pains, headache, and dyspepsia. Sildenafil is a well-tolerated and potentially efficacious oral treatment for ED in men with diabetes mellitus.
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PMID:Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men. 979 81

The efficacy and safety of oral sildenafil citrate for the treatment of erectile dysfunction (ED) were assessed in a 12-week placebo-controlled study. Men with ED of organic, psychogenic, or mixed aetiology were randomised to placebo (n = 166) or 50 mg sildenafil (n = 163), with adjustment to 100 mg or 25 mg based on efficacy and tolerability. Efficacy assessments included a global efficacy question, event log data, and an optional partner questionnaire. At the end of the study, improved erections were reported by 74% of patients receiving sildenafil versus 16% for placebo (p < 0.0001). In the final 4 weeks of treatment, 65% of all attempts at sexual intercourse were successful for all patients (responders and non-responders) receiving sildenafil versus 20% for placebo (p < 0.001). The mean number of successful attempts per month was 5.9 for patients receiving sildenafil versus 1.5 for those receiving placebo (p < 0.0001). The most common adverse events--headache, flushing, and dyspepsia--were generally mild to moderate in nature and rarely (< 1%) a reason for discontinuation of treatment. Oral sildenafil is an effective, reliable and well-tolerated treatment for ED of organic, psychogenic or mixed aetiology.
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PMID:Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Sildenafil Study Group. 989 70

Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus cavernosum. Chemically, it is a compound of the pyrazolo-pyrimidinyl-methylpiperazine class. Sildenafil has no direct relaxant effect on human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in this tissue. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil increases concentrations of cGMP in the corpus cavernosum, causing smooth muscle relaxation and blood flow into the penis, resulting in an erection. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. The drug is rapidly absorbed after oral administration, with absolute bioavailability of 40%. Its pharmacokinetics are dose proportional over the recommended dosage range. Maximum plasma concentrations are reached within 30 to 120 minutes after oral dosing in the fasting state. Sildenafil is cleared predominantly by the hepatic microsomal isoenzymes CYP3A4 (major route) and CYP2C9 (minor route). Clinical studies assessed the effect of sildenafil on the ability of men with erectile dysfunction to engage in sexual activity and, specifically, to achieve and maintain an erection sufficient for satisfactory sexual intercourse. Sildenafil was evaluated at doses of 25, 50, and 100 mg in randomized, double-masked, placebo-controlled clinical trials of up to 6 months' duration. The drug was administered to hundreds of patients aged 19 to 87 years having erectile dysfunction of various etiologies for a mean duration of 5 years. Sildenafil was associated with statistically significant improvement in erectile function compared with placebo. Adverse effects reported at a rate of >2% were headache, flushing, dyspepsia, nasal congestion, urinary tract infection, abnormal vision, diarrhea, dizziness, and rash. No cases of priapism were reported. The use of sildenafil is contraindicated in men who are taking organic nitrates, because of the potential for a precipitous decrease in blood pressure. Postmarketing reports and surveillance have revealed at least 39 deaths with sildenafil use in men having a history of heart disease, men taking nitrate medications, and men in poor physical health due to lack of exercise. Many of the men who experienced serious adverse effects or death had a variety of concomitant diseases and were taking multiple medications.
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PMID:Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction. 991 1

Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the effects of intravenously, intra-arterially, and orally administered doses of sildenafil on blood pressure, heart rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men, significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40- and 80-mg doses, respectively). These changes were transient and not dose related. Modest reductions in systemic vascular resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced no significant changes in cardiac index from 1-12 hours postdose between placebo- and sildenafil-treated subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80-mg intravenous dose and the 200-mg oral dose of sildenafil produced comparable plasma levels at twice the maximum therapeutic dose (recommended range, 25-100 mg). After brachial artery infusion of sildenafil (up to 300 microg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrine-induced preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in pulmonary arterial pressure (-27% at rest and -19% during exercise) and cardiac output (-7% at rest and -11% during exercise) were observed after 40-mg intravenous doses of sildenafil. Sildenafil was well tolerated by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
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PMID:Effects of sildenafil citrate on human hemodynamics. 1007 38

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)
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PMID:Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. 1007 39


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