Oral Pharmacotherapy of Erectile Dysfunction in Visual Studio .NET

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Oral Pharmacotherapy of Erectile Dysfunction
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123 Rosano GMC, Aversa A, Vitale C, et al Chronic treatment with tadala l improves endothelial function in men with increased cardiovascular risk Eur Urol 2005;47:214 222 124 Montorsi F, Corbin J, Pillips S Review of phosphodiesterases in the urogenital system: New directions for therapeutic intervention J Sex Med 2004;1: 322 336 125 Azadzoi KM, Payton T, Krane RJ, et al Effects of intracavernosal trazodone hydrochloride: animal and human studies J Urol 1990;144:1277 1282 126 Saenz de Tejada I, Ware JC, Blanco R, et al Pathophysiology of prolonged penile erection associated with trazodone use J Urol 1991;145:60 64 127 Aydin S, Odabas O, Ercan M, et al Ef cacy of testosterone, trazodone and hypnotic suggestion in the treatment of non-organic male sexual dysfunction Brit J Urol 1996;77:256 260 128 Kurt , zkardes H, Altug U, et al The ef cacy of antiserotoninergic agents in the treatment of erectile dysfunction J Urol 1994;152:407 409 129 Lance R, Costabile RA, Albo M, et al Oral trazodone for erectile dysfunction J Urol 1995;153:(Suppl473) 130 Meinhardt W, Schmitz PJM, Kropman RF, et al Trazodone, a double blind trial for treatment of erectile dysfunction Int J Impotence Res 1997;9:163 165 131 Brindley GS Cavernosal alpha-blockade: A new treatment for investigating and treating erectile impotence Br J Psychiatry 1983;143:332 337 132 Blum MD, Bahnson RR, Porter TN, et al Effect of local alpha-adrenergic blockade on human penile erection J Urol 1985;134:479 481 133 Zorgniotti AW, Le eur RS Autoinjection of the corpus
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cavernosum with a vasoactive drug combination for vasculogenic impotence J Urol 1985;133:39 41 Zorgniotti AW: Experience with buccal phentolamine mesylate for impotence Int J Impotence Res 1994;6:37 41 Goldstein I, Ferguson D Vasomax study group: Ef cacy and safety of oral phentolamine (VasomaxTM) for the treatment of erectile dysfunction using a crossover study design Int J Impotence Res 1998;10: (Suppl3),S61 Porst H, Derouet H, Idzikowski, et al Oral phentolamine (Vasomax ) in erectile dysfunction Results of a german multicenter-study in 177 patients Int J Impotence Res 1996;8:No3,117 Zorgniotti AW, Lizza EF Effect of large doses of the nitric oxide precursor L-arginine on erectile dysfunction Int J Impotence Res 1994;6:33 36 Mathers M, Klotz T, Bloch W, et al Effectiveness of oral L-arginine in the treatment of impotence in a prospective, randomized cross-over study Eur Urol 1999;35(Suppl 2), 67 Chen J, Wollman Y, Chernichovsky T, et al Effect of administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo- controlled study BJU International 1999;83:269 273 Sikora R, Sohn MH, Engelke B, et al Randomized placebo-controlled study on the effects of oral treatment with gingko biloba extract in patients with erectile dysfunction J Urol 1998;159:No5,(Suppl240) Choi HK, Seong DH, Rha KH Clinical ef cacy of Korean red ginseng for erectile dysfunction Int J Impotence Res 1995;7:181 186
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Self-Injection, Trans-Urethral and Topical Therapy in Erectile Dysfunction
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Self-Injection Therapy
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The demonstration by Virag in 1982 that intracavernous (IC) injection of papaverine produced a fullyrigid erection in normal males, introduced a new route of administration in the clinical management of pharmacologic agents for the treatment of erectile failure [1,2] Intracavernous injection of a vasoactive agent that readily produces erection has greatly simpli ed the multidisciplinary diagnostic investigations and management of erectile dysfunction (ED) Three groups of drugs are presently used for selfinjection therapy worldwide, or at least in some parts of the world These include papaverine, adrenoceptor blocking agents such as phentolamine or moxisylyte, and prostaglandin E1 (PGE1) These compounds have proven to be effective in all etiologies of erectile failure such as psychogenic, neurogenic or vasculogenic impotence Other agents that have been investigated for their suitability in self-injection therapy, but never reached the stage of of cial approval or even off-label use, comprise calcium channel blocking agents, vasoactive intestinal polypeptide, ketanserin, histamine, -adrenergic agonists, nitric oxide donors (linsidomine or sodium nitroprusside) etc Generally speaking, compounds that were able to relax the smooth muscle cells of both the penile arteries and the cavernous tissue, subsequently resulting in blood engorgement of the cavernous sinusoidal spaces, with activation of the veno-occlusive mechanism through compression of the subtunical veins, may be
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principally considered for self-injection therapy in ED Up to 1998, self-injection therapy was the only effective pharmacologic treatment in ED and was considered a rst-line option in this indication But with the launch of sildena l (Viagra ) IC self-injection therapy became generally a second-line option for the majority of ED patients, with the exception of those men in whom phosphodiesterase-5 (PDE-5) inhibitors were contraindicated, or turned out to be ineffective In the following, the essential features of those compounds are described, which are either approved and/or mostly used, even in off-label use, for self-injection therapy
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The effect of PGE1 on the human corpus cavernosum (CC) was rst described in 1975 by Karim & Adaikan [3] Of more than 30 prostaglandins tested in vitro on the human CC, PGE1 is the only compound that produced relaxation conducive for erection [4] All other prostaglandins produced either a dual effect (contraction and relaxation) or contraction only The relaxant effect of PGE1 on the human CC has been further demonstrated in vitro [5,6] Initial studies on the effectiveness and mechanism by which IC administration of PGE1 produced erection were very encouraging [7 10] Several investigators have assessed, in large groups of patients, the effectiveness of PGE1 for the treatment of erectile failure in man
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Self-Injection, Trans-Urethral and Topical Therapy in Erectile Dysfunction PGE1-induced relaxation of CC muscle is mediated through the activation of EP prostaglandin receptors and subsequent activation of the membrane bound adenylate cyclase, resulting in an increase in intracellular concentrations of cAMP in the cavernous tissue [11] Further consequences of the PGE1-mediated relaxation of human CC are the activation of maxi K channels, resulting in hyperpolarization and changes in transmembrane Ca2+ ux [12] These effects are complimented by the ability of PGE1 to inhibit the release of noradrenaline from sympathetic nerve endings and to suppress angiotensin II secretion in the cavernosal tissues [13,14] (Fig 81) Intracavernous injection of PGE1 has de nite advantages over the use of other drugs, such as the mixture of papaverine/phentolamine PGE1 is readily metabolized in the body by 15-hydroxyprostaglandin dehydrogenase, an enzyme that was identi ed in the human CC ([6] The enzymic degradation of PGE1 within the human CC probably contributes to the remarkably low incidence of undesirable side effects, such as prolonged erection and priapism PGE1 was also shown to suppress the collagen syn-
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thesis by TGF-beta 1 in cultured human CC, suggesting that PGE1 may play a key role in modulation/ prevention of collagen synthesis with subsequent brosis of the CC [17] This suppressive effect correlates well with the low incidence of local brotic lesions reported in PGE1-injected primates and ED patients [15,18,19] (Table 82) and the unaltered intracavernous structures in patients with biopsies performed after intracavernous PGE1 injection [20] In the meta-analysis involving literature review and personal experience in 4577 patients with erectile failure, PGE1 showed a response rate of more than 70% (Table 81) and compared to the mixture of papaverine and phentolamine, a considerably lower risk of priapism (035% versus 6%, respectively) as well as of local brotic complications such as penile nodules, indurations, or brosis during long-term injection therapy [15] Intra-penile pain or tension following intracavernosal injection of PGE1 is the other most frequently reported complaint in 72% of patients (Table 82) Except for rare cases of blood pressure decrease, no systemic side effects were observed after intracavernous injection of PGE1 [15]
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PGE1 Adrenergic nerve EP Rec Endothelial cell Stimulation Ang I Inhibition NE release 1-receptor Converting enzyme Ang II
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