A retrospective, study of prescribing for erectile dysfunction in a UK population during 1997-2000: demand was neither excessive nor continuing to rise.

Sullivan F, Donnelly L, Donnan P.

Tayside Centre for General Practice, University of Dundee, Kirsty Semple Way, UK. f.m.sullivan dundee.ac.uk

PURPOSE: The UK NHS restricted the prescription of sildenafil to a range of clearly defined clinical situations. We describe the pattern of pharmaceutical management of erectile dysfunction (ED) during the period when the new drug was introduced and then regulated. METHODS: We studied the population of males aged over 16 (n = 121,783) who were continuously registered with 60 practices in Tayside between 1 October 1997 and 30 June 2000 using record linkage and case-note verification. The patients' GPs allowed a research nurse to examine the records of these patients for demographic details, comorbidities and resource use. RESULTS: Five hundred and fifty five patients received 2493 prescriptions for alprostadil or sildenafil. The addition of an oral agent to the available therapies in 1998 did lead to a more rapid rise in prescribed treatments but this reached a plateau 3.47 per 1000 adult males per quarter after 12-15 months. Fifty eight per cent of the men had a comorbidity associated with ED. More comorbidities were found in men aged 50-69 and those living in areas of greater deprivation. Depression was a more common comorbidity in younger patients and more men from affluent areas were prescribed sildenafil following prostatectomy. CONCLUSIONS: In the Tayside region of the UK, the introduction of an effective, acceptable oral therapy for erectile dysfunction led to a rise in prescriptions issued for ED. This rise appeared to stop after 12-15 months, perhaps partly because of the governmental restrictions imposed. Copyright 2003 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15317037&dopt=Abstract sildenafil Viagra online



Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study.

Park JW, Mrowietz C, Chung N, Jung F.

Department of Internal Medicine, Division of Cardiology, Angiology, Nephrology, Hoyerswerda Hospital, Germany.

Endothelial dysfunction of precapillary arterioles impairs nutritional microcirculation at rest as well as during post-ischemic reactive hyperemia. In this monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study we investigated the acute effect of 50 mg sildenafil, a selective PDE-5 inhibitor, on resting and post-ischemic capillary circulation in twenty patients with angiographically confirmed coronary artery disease not taking nitrates or NO-donors. Mean erythrocyte velocity in digital nail-fold capillaries was determined before and after sildenafil and placebo, both baseline and after a three-minutes supra-systolic occlusion of the upper arm. Primary efficacy parameter was the drug effect on peak velocity during reactive hyperemia (peak velocity: V(max)). Post ischemic maximal capillary erythrocyte velocity V(max) significantly increased by 47% one hour after 50 mg sildenafil (mean value+/-standard deviation: 0.85+/-0.42 mm/s vs. 0.58+/-0.18 mm/s at baseline, p=0.0023), whereas placebo had no effect (p=0.5248). The difference between sildenafil and placebo was significant (p=0.0129) and sildenafil's effect can be regarded as biometrically highly relevant with standardized difference according to Cohen of 0.81. In spite a small decrease of both systolic and diastolic blood pressure after sildenafil, sildenafil significantly increased capillary erythrocyte velocity at rest. CONCLUSION: A single oral dose of sildenafil significantly increased resting and post-ischemic cutaneous capillary circulation in patients with coronary artery disease. Future studies should assess whether sildenafil also improves nutritional capillary blood flow in other organs and in other diseases with impaired endothelial function and microcirculation, for example in diabetic microangiopathy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15322323&dopt=Abstract sildenafil Viagra online



Efficacy of sildenafil citrate in treatment of erectile dysfunction: effect of type 2 diabetes.

El-Sakka AI.

Department of Urology, Suez Canal University, Ismailia, Egypt. aielsakka yahoo.com

PURPOSE: To assess efficacy of sildenafil citrate in treatment of erectile dysfunction: effect of type 2 diabetes. MATERIALS AND METHODS: A total of 466 male patients with erectile dysfunction (ED) were enrolled in this study. Of them 382 were diabetic and 84 were non-diabetic. Patients were screened for ED using the erectile function domain of the International Index for Erectile Function (IIEF). Patients underwent routine laboratory investigations, in addition to total testosterone and prolactin assessment. To assess the effect of diabetes on efficacy of sildenafil, we compared the pre and post sildenafil responses to erectile function domain, Q3, Q4. Overall satisfaction and global efficacy question (GEQ) were also assessed. RESULTS: Mean age +/- S.D. was 53 +/- 8.4 and 49.7 +/- 10.6 years for patients with and without diabetes respectively. There were significant associations between increased severity of ED and longer duration, poor metabolic control and presence of more than one diabetes-related complication (p < 0.05 for each). Differences were significant between pre and post sildenafil administration regarding erectile function domain, Q3, Q4 (p < 0.05 for each). In the non-diabetic patients the GEQ and the overall satisfaction were significantly higher than in diabetics (p < 0.05 for each). Global efficacy question was significantly low in patients with fair and poor metabolic control, longer duration of diabetes, and patients with diabetic complications (p < 0.05 for each). CONCLUSIONS: Sildenafil is an effective treatment for diabetic patients with ED. Although the efficacy of sildenafil was negatively affected by factors as poor control and longer duration of diabetes and presence of more than one diabetes-related complication, however, the global efficacy and the overall patients' satisfaction were high.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15363568&dopt=Abstract sildenafil Viagra online



Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms.

Castro MM, Rizzi E, Rascado RR, Nagassaki S, Bendhack LM, Tanus-Santos JE.

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, Brazil, 14049-900.

Statins have cholesterol-independent effects including an increased vascular nitric oxide (NO) activity and are commonly used by patients with cardiovascular disease. Such patients frequently have erectile dysfunction, which may be treated with sildenafil, a selective inhibitor of phosphodiesterase type 5. Since statins and sildenafil can activate the NO-cGMP pathway, we investigated whether pre-treatment with atorvastatin (0, 5 and 30 mg/kg/day) for 2 weeks affects sildenafil (1 pM-100 mM)-induced relaxation of aortic rings isolated from Wistar rats. We also examined the hemodynamic consequences of this interaction in Wistar rats. Plasma nitrite/nitrate (NOx) concentrations were determined using an ozone-based chemiluminescence assay. While pre-treatment with atorvastatin increased the potency of sildenafil-induced vasorelaxation (P<0.01), no differences were observed in the maximum sildenafil-induced relaxation. Pre-incubation of aortic rings with NG-nitro-L-arginine methyl ester (L-NAME) reversed atorvastatin-induced increase in the potency of sildenafil relaxation. In addition, pre-treatment with atorvastatin enhanced plasma NOx concentrations and sildenafil-induced hypotension and tachycardia (all P<0.05). These results suggest that atorvastatin increases the vascular sensitivity to sildenafil through NO-mediated mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15363994&dopt=Abstract sildenafil Viagra online



Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans.

Madsen JL, Sondergaard SB, Fuglsang S, Rumessen JJ, Graff J.

Dept. of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, University Hospital of Copenhagen, Copenhagen, Denmark.

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15370682&dopt=Abstract sildenafil Viagra online



Structure elucidation of sildenafil analogues in herbal products.

Blok-Tip L, Zomer B, Bakker F, Hartog KD, Hamzink M, Ten Hove J, Vredenbregt M, De Kaste D.

Centre for Quality of Chemical-Pharmaceutical Products, National Institute for Public Health and the Environment, PO Box 1, NL-3720 BA Bilthoven, The Netherlands.

The structure of unknown compounds present in herbal products was elucidated using liquid chromatography-electrospray ionization-mass spectrometry, direct-infusion electrospray ionization-mass spectrometry, and nuclear magnetic resonance. Compounds 1-3 were identified as sildenafil analogues, 1 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine, and an acetyl group instead of the sulfonyl group, named acetildenafil, 2 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine (homosildenafil), and 3 bearing an N-hydroxylethylpiperazine moiety instead of an N-methylpiperazine, named hydroxyhomosildenafil. When analysing products marketed for penile erectile dysfunction or marketed as aphrodisiacs, attention should be given to the possible presence of these components.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15370823&dopt=Abstract sildenafil Viagra online



The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis.

Dishy V, Cohen Pour M, Feldman L, Naftali T, Baumer M, Efrati S, Golik A, Horne T, Weissgarten J.

Division of Nephrology, Assaf Harofeh Medical Center, Zerifin 70300, Israel. vdishy zahav.net.il

BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15371988&dopt=Abstract sildenafil Viagra online



The female partner's satisfaction with sildenafil citrate treatment of erectile dysfunction.

Ichikawa T, Takao A, Manabe D, Saegusa M, Tanimoto R, Aramaki K, Yamamoto M, Okazaki T.

Department of Urology, Jyuzen General Hospital, 1-5 Kitashin-machi, Nihama, Ehime 792-8586, Japan. ichitochi yahoo.co.jp

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15379940&dopt=Abstract sildenafil Viagra online