Viagra scientific update |
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Pharmacol Res. 2008 Jun;57(6):456-63.
Aboutabl ME, Raafat M, Maklad YA, Kenawy SA, Din AG.
Department of Medicinal and Pharmaceutical Chemistry, Pharmaceutical and Drug Industries Research Division, Cairo, Egypt.
Sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in nitric oxide-deficient hypertensive rats: Role of nitric oxide-cyclic GMP pathway.
The association of erectile dysfunction (ED) with cardiovascular diseases is so common. This study was carried out to investigate possible impact of sildenafil; the prototype phosphodiesterase 5 inhibitor used for treatment of ED, on the beneficial hemodynamic and histopathological effects of the prototype third generation calcium antagonist, amlodipine, in nitric oxide (NO)-deficient hypertensive rats. Hypertension was induced by 4-weeks treatment with N(omega)-nitro-l-arginine-methyl ester (l-NAME). Animals were allocated into five groups: normal control, hypertensive control, amlodipine-treated group, sildenafil-treated group and combined treatment group. Drug treatment was started 2 weeks after l-NAME and continued together with l-NAME to the end of the treatment period. Systolic blood pressure (SBP), plasma nitrate/nitrite (NO(x)) and plasma cGMP levels were evaluated at the end of the treatment period. Aortic and renal structural alterations were also investigated. l-NAME treatment caused elevation of SBP, reduction in plasma NO(x) and cGMP levels as well as adverse histological alterations in the tissues studied. Amlodipine normalized SBP, restored plasma NO(x) and cGMP levels and ameliorated the adverse histological changes seen in NO-deficient rats. When combined with sildenafil, both hemodynamic and histopathological effects of amlodipine were augmented with an underlying enhanced elevation of both plasma NO(x) and cGMP levels to statistically higher values than amlodipine alone. These results show that sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in NO-deficient hypertensive rats with a pivotal role being played by NO-cGMP pathway. Whether this pharmacodynamic interaction could exist in other models of hypertension that do not share such biochemical derangement warrants further investigations.
Int J Gynaecol Obstet. 2008 Aug;102(2):115-9.
Cavalcanti AL, Bagnoli VR, Fonseca AM, Pastore RA, Cardoso EB, Paixão JS, Soares JM Jr, Saad F, Baracat EC.
Department of Obstetrics and Gynecology, University of São Paulo, Brazil.
Effect of sildenafil on clitoral blood flow and sexual response in postmenopausal women with orgasmic dysfunction.
OBJECTIVE: To analyze the effects of sildenafil citrate on clitoral blood flow and sexual response in postmenopausal women with orgasmic dysfunction. METHOD: In this randomized, double-blind, placebo-controlled trial 22 women received a 50-mg dose of sildenafil (n=11) or placebo (n=11) daily for 15 days. The Golombok Rust Inventory of Sexual Satisfaction (GRISS) was used for subjective evaluation of the sexual-response cycle. Clitoral blood flow was measured by color and pulse Doppler at baseline, after 1 hour of taking the first dose, and after 15 days of treatment. RESULTS: Blood flow was significantly more improved in the sildenafil than in the placebo group (P<0.05), and a positive correlation between Doppler values and GRISS scores was noted in the sildenafil group after only 15 days of treatment. CONCLUSION: Sildenafil may improve clitoral blood flow and increase the GRISS scores in postmenopausal women with orgasmic dysfunction.
Urology. 2008 Jul 1.
McVary KT, Siegel RL, Carlsson M.
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Sildenafil Citrate Improves Erectile Function and Lower Urinary Tract Symptoms Independent of Baseline Body Mass Index or LUTS Severity.
OBJECTIVES: To evaluate the body mass index (BMI) and lower urinary tract symptom (LUTS) severity on treatment response to sildenafil in men with erectile dysfunction (ED) and moderate to severe LUTS associated with benign prostatic hyperplasia. METHODS: A post hoc analysis of data from a 12-week, double-blind, placebo-controlled study of sildenafil (50 mg once daily titrated to 100 mg once daily) was conducted. The BMI categories were obese (>/=30 kg/m(2)), overweight (>/=25 to <30 kg/m(2)), and normal weight (<25 kg/m(2)). ED was defined as a score of /=12. The maximal urinary flow rate was determined by uroflowmetry. RESULTS: Patients receiving sildenafil (n = 189) had a significant improvement in the erectile function domain scores of the International Index of Erectile Function (P < .0001 vs placebo, n = 180), which did not vary across BMI groups. A greater improvement in LUTS score was observed with sildenafil compared with placebo for men with severe LUTS (-8.6 vs -2.4, P < .0001) than in men with moderate LUTS (-3.6 vs -1.7, P = .06). Also, the improvement in LUTS scores was significant (P
Curr Opin Investig Drugs. 2008 Jul;9(7):754-9.
Bednar MM.
Pfizer Inc, Pfizer Global Research and Development, 50 Pequot Avenue, MS 8260-2604, New London, CT 06320, USA.
The role of sildenafil in the treatment of stroke.
The structural underpinning responsible for neuroplasticity and neurorestoration under physiological and pathophysiological conditions is only beginning to be elucidated. It is evident that life-long neurogenesis occurs in the human brain, with experimental data supporting its upregulation following an insult (eg, stroke) and/or in response to pharmacological therapy. Sildenafil, a PDE5 inhibitor currently marketed for the treatment of erectile dysfunction, enhances neurorestoration in rat models of stroke, as measured by neurogenesis, synaptogenesis and angiogenesis. This neurorestorative effect is associated with improved outcome despite no observed effect on brain infarct size. This neurorestorative effect has also been observed in both young and old animals, and is demonstrable even if therapy is initiated 1 week post-stroke. The extended therapeutic window and novel mechanism of action of neurorestorative therapies, such as sildenafil, warrant further investigation for the treatment of stroke.
Pak J Pharm Sci. 2008 Jul;21(3):275-81.
Ali ST.
Department of Physiology, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia.
Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual responses in Saudi men with erectile dysfunction in routine clinical practice.
Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction, yet enhanced satisfaction has been infrequently assessed in the sexual trials. We evaluated the efficacy of sildenafil vs. tadalafil, in Saudi men with erectile dysfunction and determined the self-based rating of medicinal preference. Sildenafil citrate (Viagra) is a potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Whereas cGMP is a second messenger for the vasodilator effects of nitric oxide causing smooth muscle relaxation, which in turn leads to penile erection; however the mechanism by which cGMP stimulates relaxation of the smooth muscles remains to be elucidated. Both sildenafil and tadalafil have a rapid onset with the effectiveness up to 4 hours and 36 hours respectively. In this study subjects treated with 100 mg oral dose of sildenafil / 20 mg tadalafil were found to be associated with higher mean scores for the questions of the International Index of Erectile Function (IIEF). Frequency of penetration and maintenance of erection after sexual penetration and/or during masturbation were found to be enhanced significantly (p<0.001) in both sildenafil/tadalafil treated men. Similarly mean domain of erectile function, orgasmic function, and intercourse satisfaction also showed a significantly positive improvement (p/0.001) in both the treated groups in comparison with their age matched untreated controls. Interestingly in all the cases, tadalafil group showed considerably greater positive responses than the sildenafil group but within the same significant levels. Strikingly the sexual-desire domain in sildenafil treated men with respect to their aged matched controls showed a non-significant difference, where as this difference was found to be highly significant in tadalafil treated group. Similarly mean scores for the overall satisfaction domains of the IIEF in comparison with the untreated subjects showed a significant positive response in the sildenafil treated group (p<0.001), where as tadalafil treated group showed a highly significant positive response (p<0.005). These findings suggest that both sildenafil and tadalafil may assist an individual in extending/enhancing the excitement phase or prolonging the sexual interaction. These studies further conclude that there is a major point of difference between the short-acting agent sildenafil and the longer acting tadalafil. This probably allows more choice about the onset of sexual responses with tadalafil than with sildenafil.
J Sex Med. 2008 Jul 1.
Goldstein I, Mulhall JP, Bushmakin AG, Cappelleri JC, Hvidsten K, Symonds T.
Sexual Medicine, Alvarado Hospital, University of California, San Diego, CA, USA.
The Erection Hardness Score and Its Relationship to Successful Sexual Intercourse.
Introduction. The Erection Hardness Score (EHS), recently validated, was developed in 1998 as a simple (one-item) method to quantify erection outcome data. Although it is intuitive that erection hardness and successful sexual intercourse (SSI) are related, the link has not been directly established. Objective. To evaluate the relationship between erection hardness (assessed by EHS) and SSI, establishing the EHS as a clinically useful tool. Methods. The data set (N = 307) was from a multinational, double-blind, placebo-controlled trial (with open-label extension) of sildenafil citrate in men with erectile dysfunction. Main Outcome Measures. Event-based modeling used every intercourse attempt and the EHS to estimate the odds ratio of SSI between adjacent EHS categories. Mean-based modeling used mean EHS per patient to determine its relationship to percentage of SSI. Mediation-based modeling used mean EHS and mean percentage of SSI over the double-blind phase to estimate the direct effect of sildenafil treatment on SSI and the indirect effect of sildenafil treatment on SSI via erection hardness. Results. The odds of SSI for EHS 3 (hard enough for penetration but not completely hard) were 41.9 times (95% confidence interval [CI], 33.0-53.2; P < 0.0001) that for EHS 2 (hard but not hard enough for penetration), and the odds of SSI for EHS 4 (completely hard and fully rigid) were 23.7 times (95% CI, 19.5-28.9; P < 0.0001) that for EHS 3. The percentage of SSI increased approximately curvilinearly with the increase in mean EHS, from almost 60% at EHS 3 to 78.5% at EHS 3.5 and to 93.1% at EHS 4. The indirect effect of sildenafil treatment on SSI via erection hardness accounted for almost 90% of the total effect on SSI (P < 0.0001). Conclusion. The close and direct relationship between erection hardness and SSI supports the broader use of the EHS-a simple, valid, reliable, and responsive measure-in clinical practice.
JAMA. 2008 Jul 23;300(4):395-404.
Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S.
Department of Psychiatry, University of New Mexico School of Medicine, 2400 Tucker NE, MC 09 5030, Albuquerque, NM 87131-0001, USA.
Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial.
CONTEXT: Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women. OBJECTIVE: To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women. DESIGN, SETTING, AND PARTICIPANTS: An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction. INTERVENTION: Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity. MAIN OUTCOME MEASURES: The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed. RESULTS: In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects. CONCLUSION: In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects.
Pulm Pharmacol Ther. 2008 Jul 9.
Voswinckel R, Reichenberger F, Enke B, Kreckel A, Krick S, Gall H, Schermuly RT, Grimminger F, Rubin LJ, Olschewski H, Seeger W, Ghofrani HA.
Department of Internal Medicine, University of Giessen Lung Center, University Hospital Giessen and Marburg GmbH, Giessen, Germany.
Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.
BACKGROUND: Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. METHODS AND PATIENTS: Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15mug; n=25 or 30mug; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). RESULTS: Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. CONCLUSION: The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.
Int J Cardiol. 2008 Jul 28.
Guazzi M, Arena R, Pinkstaff S, Guazzi MD.
University of Milano, San Paolo Hospital, Cardiopulmonary Laboratory, Cardiology Division, University of Milano, San Paolo Hospital, Milano, Italy.
Six months of Sildenafil therapy improves heart rate recovery in patients with heart failure.
Previous research has demonstrated an increase in large vessel stiffness in patients with heart failure (HF). Furthermore, heart rate recovery (HRR) may be negatively impacted by increased arterial stiffness secondary to altered baroreceptor discharge. The purpose of the present study was to determine if chronic phosphodiesterase 5 (PDE5) inhibition with Sildenafil, previously shown to improve arterial stiffness, favorably impacts HRR in patients with HF. Forty male subjects (age: 65.3+/-7.3 years, baseline ejection fraction: 37.1+/-7.4%, 15 non-ischemic HF/25 ischemic HF) participated in this study. Subjects received Sildenafil (25 mg, 3 times/day) for six months. Symptom-limited exercise testing was performed at baseline and six months with a lower extremity ergometer. Heart rate recovery was defined as HR at maximal exercise minus HR at 1 min recovery. No adverse effects were reported throughout the study period. Paired t-testing revealed that HRR was significantly improved following six months of Sildenafil therapy (baseline: 17.5+/-3.5 bpm vs. Post: 20.6+/-3.2 bpm). The results of the present study indicate that chronic Sildenafil therapy significantly increases HRR, an important prognostic marker, in patients with HF. A plausible mechanism for the improvement of HRR is the previously demonstrated impact Sildenafil has on arterial stiffness and therefore baroreceptor function.
J Intensive Care Med. 2008 Aug 12.
Lee JE, Hillier SC, Knoderer CA.
Dept of Pharmacy.
Use of Sildenafil to Facilitate Weaning from Inhaled Nitric Oxide in Children with Pulmonary Hypertension following Surgery for Congential Heart Disease.
Pulmonary hypertension frequently complicates the postoperative management of patients after congenital cardiac surgery. Inhaled nitric oxide is an effective treatment option, but rebound pulmonary hypertension can occur upon its withdrawal. Sildenafil may facilitate its withdrawal by restoring cyclic guanosine monophosphate availability via phosphodiesterase-5 inhibition. The purpose of this study was to evaluate the use of sildenafil in facilitating weaning from inhaled nitric oxide after congenital cardiac surgery in patients who had previously failed weaning, and to compare the effects of sildenafil on pulmonary and systemic hemodynamics. Children who received sildenafil after cardiovascular surgery during a 23-month period at Riley Hospital for Children were identified. Medical records were retrospectively reviewed to determine sildenafil and nitric oxide dosing, pulmonary and systemic blood pressures, and adverse effects. Oral sildenafil was administered to 7 children who had failed attempts at inhaled nitric oxide weaning. Inhaled nitric oxide was weaned from 29.8 +/- 5.9 ppm prior to sildenafil initiation to 12.2 +/- 3.4 ppm (mean +/- SE; P = .024) in the 24 hours after sildenafil. Mean pulmonary artery and systemic arterial pressure were unchanged from baseline when measured 1 hour after sildenafil dosing (mean pulmonary artery pressure, 29 +/- 1 to 27 +/- 0.7 mm Hg, P = .066; mean systemic arterial pressure, 56 +/- 1.2 to 54 +/- 1.2 mm Hg, P = .202). Sildenafil may facilitate withdrawal of inhaled nitric oxide and prevent rebound pulmonary hypertension in patients previously failing inhaled nitric oxide weaning attempts.
Curr Drug Saf. 2007 Jan;2(1):5-8.
Böhm M, Burkart M, Baumann G.
Department of Medicine, Cardiology, Angiology and Pneumology, University Hospital Charité, Berlin, Germany.
Sildenafil is well tolerated by erectile dysfunction patients taking antihypertensive medications, including those on multidrug regimens.
Erectile dysfunction occurs extensively among patients with arterial hypertension. We investigated the safety of sildenafil for patients with and without antihypertensive medication. Our study included data from 35 double-blind, placebo-controlled, and randomized investigations, with a total of 8115 patients. The term of therapy was between 6 weeks and 6 months, for both the sildenafil group (5-200 mg, n=4819) as well as the placebo group (n=3296). We studied the adverse events in the men who received 1 or more hypertensives (n=2388), and in those who took no antihypertensive medication (n=5727). Our findings disclosed equal frequency of adverse events in both groups, without influence by the number of different antihypertensives administered. The occurrence of AEs associated with blood pressure was slight, and was comparable between the individual groups. These results support the conclusion that sildenafil is also well tolerated by patients taking one or more antihypertensives. Patients being treated with alpha blockers should be stable on this therapy in order to minimize the possibility of orthostatic hypotension. An initial dose of 25 mg should furthermore be considered for these patients.
BJU Int. 2008 Aug 14.
Buvat J, Hatzichristou D, Maggi M, Farmer I, Martínez-Jabaloyas JM, Miller PJ, Schnetzler G.
Papageorgiou General Hospital and Aristotle University of Thessaloniki, Thessaloniki, Greece.
Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction.
OBJECTIVE To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED). PATIENTS AND METHODS A multicentre, parallel-group trial was conducted in two 4-week periods. In period 1, patients received 50-mg doses of sildenafil single-blinded for 4 weeks. In period 2, patients were randomized to double-blind, placebo-controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged >/=18 years with a documented clinical diagnosis of ED (score of
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Drug category:Sexual stimulants
 Viagra scientific update
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