Tadalafil: new preparation. Slightly more convenient, but poorly assessed in organic disorders.

[No authors listed]

(1) The standard oral treatment for erectile dysfunction is sildenafil, a type 5 phosphodiesterase inhibitor, whether the underlying problem is organic (for example, post prostatectomy or spinal cord damage) or psychological. (2) Another inhibitor of the same type, tadalafil, has been available in France since early 2003. (3) At 10 mg to 20 mg, tadalafil is more effective than placebo, including in diabetic patients. But placebo-controlled trials have included few patients with a history of total prostatectomy, spinal cord damage, or sildenafil failure. One trial, which was not published in detail, reported that the effects last more than 12 hours. But the European Medicines Evaluation Agency considered that the reported data did not support this conclusion. There was no significant difference between active treatment and placebo groups after 12 hours. The risk-benefit ratio of long term treatment with tadalafil is unknown. (4) The two available comparative trials do not rule out the possibility that tadalafil is less effective than sildenafil. (5) Known adverse effects and drug interactions are similar in both tadalafil and sildenafil. Both drugs are contraindicated in patients using nitrate derivatives, because of a risk of abrupt hypotension. (6) Unlike sildenafil, administration of tadalafil does not retard its action. (7) In practice, sildenafil remains the first line option for treating erectile dysfunction with an organic cause. Tadalafil is slightly easier to use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14986690&dopt=Abstract sildenafil Viagra online



Effects of nitric oxide on the Ca2+-activated potassium channels in smooth muscle cells of the human corpus cavernosum.

Lee SW, Kang TM.

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. drswlee smc.samsung.co.kr

Relaxation of the corpus cavernosum smooth muscle is an absolute prerequisite of penile erection. Potassium channels play a role in the physiologic regulation of corporal smooth muscle tone. Among the several subtypes of potassium channels, Ca2 +-activated potassium channel (KCa channel) subtypes are thought to be the most physiologically relevant in the regulation of corporal smooth muscle tone. The purpose of this study was to investigate the effects of nitric oxide (NO) and sildenafil on the KCa channels and elucidate the mechanisms of action on the KCa channels in smooth muscle cells of the human corpus cavernosum. The conventional patch-clamp technique was applied to short-term cultured smooth muscle cells of the human corpus cavernosum. Single-channel currents were recorded in cell-attached or inside-out patches, and whole-cell currents were recorded in perforated-patches. In cell-attached patches, sildenafil alone did not activate the KCa channels but sildenafil enhanced the NO-induced activation of KCa channels. The open probability of KCa channels was increased significantly after application of NO donor, SIN-1 (100 microM) (47 +/- 7.1%, n = 10, P=0.002). The application of sildenafil (100 nM) with SIN-1 (100 microM) markedly increased the open probability of KCa channels (148 +/- 24%, n = 8, P < 0.001). The activation by SIN-1 or sildenafil with SIN-1 was completely blocked by pretreatment of the soluble guanylate cyclase inhibitor, ODQ (10 microM). In inside-out patches. SIN-1 or sildenafil with SIN-1 failed to activate KCa channels at pCa 7.5 (n=5). SIN-1 increased the whole cell outward K+ currents in all holding potential. The increased IK by SIN-1 was inhibited by charybdotoxin (CTX) about 70%. These data provide compelling evidence consistent with the involvement of the KCa channel subtype in modulating NO-induced relaxation responses in human corporal smooth muscle. Furthermore, the activation of KCa channels is thought to be mediated by activation of soluble guanylate cyclase, leading to increased intracellular levels of cyclic GMP and the subsequent activation of protein kinase rather than direct NO effect.

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Effect of sildenafil on ocular haemodynamics.

Dundar SO, Dundar M, Kocak I, Dayanir Y, Ozkan SB.

Department of Ophthalmology, Adnan Menderes University, Aydin, Turkey. orucs hotmail.com

PURPOSE: To study the effect of sildenafil, which is an effective agent for the treatment of erectile dysfunction, on ocular haemodynamics. METHODS: In this prospective study we examined the effect of a single oral dose of 50 mg sildenafil (Viagra) in a group of healthy young male volunteers, by using colour Doppler ultrasound imaging to measure haemodynamic variables in the central retinal artery (CRA), short temporal posterior ciliary artery (STPCA) and ophthalmic artery (OA). The following examinations were performed on both eyes immediately before and 1 h after a single oral dose of 50 mg sildenafil: visual acuity, intraocular pressure (IOP), colour vision, anterior segment, fundus appearance, resting heart rate, blood pressure and colour Doppler measurements. RESULTS: After sildenafil administration, peak systolic velocity, mean velocity and end-diastolic velocity significantly increased in the OA of both eyes. All Dopper indices remained non-significant for the CRA and STPCA of both eyes. Sildenafil did not cause any significant change in IOP, colour vision, visual acuity, systolic blood pressure or diastolic blood pressure. However, heart rate measurements increased significantly after sildenafil administration compared with baseline (p = 0.003). CONCLUSION: The increased flow velocity in the ophthalmic artery seems to be due to a vasodilator effect of sildenafil.

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Determination of transdermal sildenafil in nude mouse skin by reversed-phase high-performance liquid chromatography.

Lia J, Chang TW.

Department of Pharmaceutics, School of Pharmacy, Taipei Medical University, Taiwan. jhorng tmu.edu.tw

A simple and sensitive high-performance liquid chromatographic method was developed for the determination of sildenafil transdermal permeation of nude mouse skin. A reversed-phase column with UV detection at 224 nm was used for chromatographic separation. The mobile phase consisted of 32% acetonitrile with 0.2% phosphoric acid in water at pH 5.3 adjusted with 10 M NaOH with the flow-rate set at 1.0 ml/min. The limit of quantitation achieved was 5 ng/ml, and the calibration curve showed good linearity over the concentration range of 5-500 ng/ml. The relative standard deviations of within- and between-day analyses were all within 15%. Sildenafil was found to be stable between pH 3 and 12 during 24-h incubation with skin. After transdermal administration of 15.8 microg/ml of sildenafil to nude mouse skin, it was detected as early as 15 min. The transport amount of sildenafil could be quantitated and, at pH 8-11, had the highest permeation rate in nude mouse skin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11767309&dopt=Abstract sildenafil Viagra online



Prognostic factors for response to sildenafil in patients with erectile dysfunction.

Martinez-Jabaloyas JM, Gil-Salom M, Villamon-Fort R, Pastor-Hernandez F, Martinez-Garcia R, Garcia-Sisamon F.

Department of Urology, Hospital Clinico Universitario, Valencia, Spain. jaba pulso.com

OBJECTIVE: To assess the clinical efficacy of sildenafil as treatment for erectile dysfunction (ED) the factors associated with treatment failure were investigated. METHODS: Open, prospective study including 244 patients suffering from ED who were evaluated by anamnesis, physical exploration, blood test, dynamic penile color duplex ultrasonography and Sexual Health Inventory for Male (SHIM). The efficacy of sildenafil was assessed by repeating the SHIM 2 months after therapy, independent of the final dose used. Side effects were also recorded. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. RESULTS: Overall, sildenafil was effective in 56.8% of 213 eligible patients. When the etiologic diagnosis was not included in the multivariate analysis, antecedents of diabetes mellitus, non-nerve-sparing radical prostatectomy and SHIM basal score were selected as predictors of a poor response. In a second analysis including etiologic diagnosis, only SHIM basal score and etiological diagnosis proved to be of prognostic value. Side effects were noticed by 24.4% of patients, none of them being severe. CONCLUSIONS: Sildenafil is a rather effective and well-tolerated treatment for ED. The basal severity of ED and etiological diagnosis are the prognostic factors most significantly associated with treatment outcome.

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Sildenafil induces retinal vasodilatation in healthy subjects.

Pache M, Meyer P, Prunte C, Orgul S, Nuttli I, Flammer J.

University Eye Clinic Basel, Switzerland.

BACKGROUND: The cardiovascular effects of sildenafil (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration of sildenafil on the retinal vessel diameters of healthy subjects was evaluated. METHODS: Sildenafil 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes after sildenafil uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes after sildenafil uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION: Sildenafil causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated.

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[Effects of icariin on intracavernosal pressure and systematic arterial blood pressure of rat]

[Article in Chinese]

Tian L, Xin ZC, Yuan YM, Fu J, Liu WJ, Wang LL.

Department of Urology, People's Hospital affiliated to Wuhan University, Wuhan 430060, China.

OBJECTIVE: To realize the effect of icariin on erectile function of penis. METHODS: After the cavernous nerve (CN) of rat was isolated unilaterally, the corpora cavernosa (CC) and right carotid artery were exposed. A 26G needle catheter was inserted into the right CC to monitor the intracavernous pressure (ICP), and another 26G needle catheter was inserted into the left CC for drug administration. Another catheter was placed into the carotid artery to monitor mean systematic arterial blood press (MBp). Icariin of different concentrations was administrated intracavernosally, and the ICP and MBp were recorded during electric stimulation on CN. Sildenafil and papaveine were used as controls. The effects of nitric oxide syntheses (NOS) inhibitor N(omega)-nitro-L-arginine (LNNA), and soluble guanylate cyclase inhibitor H-[1,2,4] oxadiazolo [4,3,-a] quinoxalin-1-one (ODQ) on icariin (10(-4)mol/L) induced ICP changes were investigated also. RESULTS: Icariin, sidenafil and papaverine increased the ICP in a dose-depended manner (P < 0.01). Icariin and sildenafil did not influence the MBp (P > 0.05), however, papaverine significant influenced MBp (P < 0.01). EC(50) of Icariin, sildenafil and papaveine on ICP/MBp were 2.23 micro mol/L, 0.24 micro mol/L and 9.73 micro mol/L respectively. ODQ and LNNA significantly decreased ICP induced by icariin (10(-4)mol/L). CONCLUSION: Icariin increases ICP without influence on MBp and such effect is inhibited by LNNA and ODQ significantly. Icariin regulates the activity of NO-cGMP signal pathway on CC to enhance erectile function by oral therapy.

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SS-penogram: a new diagnostic test for erectile dysfunction.

Choi HK, Choi YJ, Choi YD, Rha KH, Kim JH, Kim DK.

Department of Urology and Institute of Andrology,Yonsei University College of Medicine, P.O. Box 1217, Seoul 135-720, Korea. ssclinic yumc.yonsei.ac.kr

The clinical reports on Sildenafil sulfate (Viagra) are mainly based on individual observations. However, there is a paucity of objective studies in the literature. In order to objectively examine the effect of Sildenafil, a SS (Sexual Stimulation)-Penogram that is a non-invasive, simple and physiologic method was developed using a radioisotope (RI). One hundred and four SS-penograms were performed on patients who had a documented erectile dysfunction (ED) lasting for more than 6 months. After an intravenous injection of 99mTc-RBC (15 mCi), the first penogram was taken immediately after sexual stimulation, which was done by 30 minutes of erotic videotape viewing. Forty minutes after administering 25 to 100 mg of Sildenafil, a second penogram was taken. The characteristics of each penogram were analyzed according to a previously reported method. The results were graded as follows; Type I(normal function; 5 min or more of peak erectile response with an induction period of 1 to 6 min), Type II-A (impossible function type; i.e., showing less than 2 times the basal radioactivity level), Type II-B (the unstable type; showing less than 5 min of peak erectile response), and Type II-C (the delayed type; which showed a delay of more than 15 min after the start of sexual stimulation). The patients were grouped according to their response after Sildenafil administration, and the effect of Sildenafil was assessed by comparing the radioactivity from between 7 to 22 minutes and the changes in the characteristics of the penogram. The mean age of the patients was 44.9 +/- 10.2 (23 - 68) years. In the first penogram, Type I was found in 12 patients, and Type II-A in 14, Type II-B in 73, Type II-C in 1 and a mixed (II-B + C) type was found in 4 patients. A second penogram after Sildenafil administration, showed Type I in 46 patients, and Type II-A in 10, Type II-B in 46 and a mixed type was found in 2 patients. The responses after Sildenafil were categorized as follows: 1) An excellent response group (consisting of 56 patients-53.9%); Those who showed greater than 50% increase in the RI area after Sildenafil treatment. 2) A good response group consisting of (23 patients-22.1%); i.e., those who showed a less than 50% but greater than a 20% increase in the RI area after Sildenafil administration. 3) A borderline group (consisting of 15 patients-14.4%); showing less than a 20% change in the RI area after Sildenafil treatment. 4) non-response group (consisting of 10 patients-9.6%). The therapeutic efficacy of Sildenafil, as determined by the SS-penograms, revealed that there was an augmentation in the erectile capabilities in 76% of men (79/104) but a non-response was observed in 9.6% (10/104). The efficacy of Sildenafil on the SS-penogram did not correlate with the patient's age (p=0.198). It is believed that the SS-penogram can be used to accurately evaluate the natural erectile status in sexual and pharmacological stimulation, and provides the most objective erectile response in any therapeutic trial. Consequently, the primary challenge for any erectile dysfunction remedy is to be able to demonstrate its efficacy. A further evaluation is warranted in the non-response group, which was not based on any severe organic dysfunction.

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