tadalafil, Cialis
Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus.

Vickers MA, Satyanarayana R.

Department of Surgery, Togus VA Medical Center, Togus, Maine 04330, USA. Martyn.Vickers med.va.gov

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12494279&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Testosterone Regulates PDE5 Expression and in vivo Responsiveness to Tadalafil in Rat Corpus Cavernosum.

Zhang XH, Morelli A, Luconi M, Vignozzi L, Filippi S, Marini M, Vannelli GB, Mancina R, Forti G, Maggi M.

Andrology Unit, Department of Clinical Physiopathology, University of Florence, V.le G. Pieraccini, 6, 50139 Florence, Italy.

OBJECTIVES:: To investigate the effect of testosterone on PDE5 expression and PDE5 inhibitor tadalafil in vivo responsiveness in a rat model. METHODS:: PDE5 expression was localized by immunohistochemistry in the rat corpus cavernosum (CC) and quantified by both real-time RT-PCR and Western blot analysis in several tissues. In the in vivo study, control, castrated and testosterone (T) supplemented castrated rats were treated with acute or chronic oral tadalafil. Erectile function was evaluated by monitoring intracavernous pressure (ICP) following electro-stimulation (ES) of the cavernous nerve and intracavernous injection of NO donor, sodium nitroprusside (SNP). RESULTS:: Rat CC expressed the highest PDE5 mRNA level. PDE5 was specifically immunolocalized in endothelial and smooth muscle cells. Surgical castration induced a significant reduction of PDE5 gene and protein expression (p<0.05), and ES response at all stimulation frequencies (p<0.001). T supplementation completely restored PDE5 expression, erectile response to ES and responsiveness to PDE5 inhibitor. Both acute and chronic tadalafil treatment were ineffective in ameliorating the ES response in castrated rats. Injection of increasing concentrations of SNP in castrated rats resulted in a statistically significant increase in ICP/MAP ratio as that observed in intact rats. In addition, tadalafil did not amplify the SNP effect in castrated rats at all the doses tested (0.06-6nmoles). CONCLUSIONS:: Our findings demonstrate that testosterone positively regulates PDE5 expression and in vivo responsiveness to PDE5 inhibitor, tadalafil, in the rat CC.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15716209&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Recreational use and misuse of phosphodiesterase 5 inhibitors.

Smith KM, Romanelli F.

Drug Information Center, College of Pharmacy, University of Kentucky, Lexington, 40536-0293, USA. ksmit1 email.uky.edu

OBJECTIVE: To characterize the rationale for and extent of phosphodiesterase (PDE) 5 inhibitor use in recreational settings, describe risks from such misuse, and discuss postexposure clinical management strategies. DATA SOURCES: Published articles identified by searches through Medline, EMBASE, International Pharmaceutical Abstracts, and Toxline, from 1990 to March 2004, using the search terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, abuse, overdose, adverse effects, recreational, and street drugs. Additional references identified within articles and information from the Internet were included. STUDY SELECTION: Clinical trials, epidemiologic reviews, case reports, and news releases concerning the misuse of sildenafil. DATA EXTRACTION: By the authors. DATA SYNTHESIS: PDE5 inhibitors, indicated for treatment of erectile dysfunction, can produce several adverse effects, including potentially fatal cardiovascular events. Reports of recreational use and misuse of sildenafil appear in the medical literature and the media. The potential for abuse also exists for the two more recently approved drugs in this class, vardenafil and tadalafil. Increasing access to these drugs via the Internet may facilitate such misuse. Use in social settings has gained popularity, both in young, healthy patients, as well as those with chronic medical conditions, including human immunodeficiency virus infections. In these settings, the PDE5 inhibitors are sometimes used concomitantly with "club drugs" such as ketamine and amyl nitrite, leading to potentially harmful or fatal drug interactions. CONCLUSION: Pharmacists should be cognizant of the potential for PDE5 inhibitors to be misused, particularly in patients who are at greater risk of cardiovascular complications, and should advise patients and other health care professionals accordingly.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15730119&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Gateways to clinical trials.

Bayes M, Rabasseda X, Prous JR.

mbayes prous.com

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12616707&dopt=Abstract tadalafil Cialis