Phosphodiesterase inhibitors erectile dysfunction

Erectile dysfunction is treated by local or systemic application of vasodilator drugs. The most effective is sildenafil, a phosphodiesterase-type 5 inhibitor. 

Recent use (within 24 h of sildenafil or vardenafil or within 48 h of tadalafil) of a phosphodiesterase-5 inhibitor for erectile dysfunction (or pulmonary hypertension)... 

Phosphodiesterase type 5 inhibitors are commonly prescribed for erectile dysfunction and include sildenafil, vardenafil,... 

Phosphodiesterase 5 inhibitors such as sildenafil are effective for MS-induced erectile dysfunction.14 In women, vaginal dryness or dyspareunia may respond to lubricating jellies. 

Sildenafil It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction. It results in reduced breakdown of cyclic guanosine monophosphate (cGMP) which is responsible for nitric acid (NO) mediated vasodilatation in corpora cavernosa. Thus inducing an erectile response to sexual stimulation. It has no direct relaxant effect on smooth muscle of corpus cavernosa and has no effect in absence of sexual stimulation. 

A combination of phentolamine with the nonspecific smooth muscle relaxant papaverine, when injected directly into the penis, may cause erections in men with sexual dysfunction. Long-term administration may result in fibrotic reactions. Systemic absorption may lead to orthostatic hypotension priapism may require direct treatment with an -adrenoceptor agonist such as phenylephrine. Alternative therapies for erectile dysfunction include prostaglandins (see Chapter 18), sildenafil and other cGMP phosphodiesterase inhibitors (see Chapter 12), and apomorphine. 

Terrett, N. K. Bell, A. S. Brown, D. Ellis, P. 1996. Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg. Med. Chem. Lett., 6,1819-1824. 

Snow KJ. Erectile dysfunction in patients with diabetes mellitus advances in treatment with phosphodiesterase Type 5 inhibitors. BrJ Diab Vase Dis 2002 2 282-287. 

Porst H, Rosen R, Padma-Nathan H, et al. Efficacy and tolerability of vardenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction the first at home clinical trial. IntJ Impot Res 2001 13 192-199. 

Jackson G, Martin E, McGing E, etal. Successful withdrawal of oral long-acting nitrates to facilitate phosphodiesterase Type 5 Inhibitor use in stable coronary disease patients with erectile dysfunction. J Sex Med 2005 2 513-516. 

Thadani U, Smith W, Nash S, et al, The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease, J Am Coll Cardiol 2002 40 2006-2012. 

Another recent example is provided by the discovery of the use of sildenafil (Viagra Fig. 1.15), a phosphodiesterase type 5 (PDE5) inhibitor, as an efficacious, orally active agent for the treatment of erectile dysfunction [25,26]. Initially, this compound was brought to the clinic as an hypotensive and cardiotonic substance, but its usefulness in erectile dysfunction resulted unexpectedly from clinical observations made during a 10-day toleration study in Wales [27]. 

A more recent example is that of sildenafil which, as a result of observations made during Phase I studies in male volunteers, is now used to treat erectile dysfunction. Sildefanil had originally been designed as an analogue of zaprinast, and a more selective phosphodiesterase inhibitor (PDE5) for use as a cardiovascular agent (see Chapter 1-1). 

Aromatic sextets are not essential for the stability of heterocyclic rings and saturated and partially-saturated rings occur widely. These are usually named as the corresponding dihydro or tetrahydro derivatives, e.g., 37-39. The fully-saturated derivatives of pyridine and pyrazine are commonly referred to as piperidine 40 and piperazine 41. The antihypertensive calcium channel antagonist nifedipine 42 is a 1,4-dihydropyridine derivative , and sildenafil 43, which contains a piperazine ring, is a phosphodiesterase inhibitor used to treat erectile dysfunction . 

UROLOGICAL DRUGS ERECTILE DYSFUNCTION Phosphodiesterase type 5 inhibitors... 

The erectile dysfunction group of drugs, of which sildenafil is most common, are potent inhibitors of cyclic guanosine monophosphate-specific phosphodiesterase type 5 (PDE-5). The other two available drugs are tadalafil (Cialis) and... 

Drugs are effective for the relief of erectile dysfunction, notably sildenafil, a highly-spedfic phosphodiesterase inhibitor. 

The combination of organic nitrates and sildenafil citrate (Viagra) can precipitate life-threatening hypotension in patients with angina (112). Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5, which causes smooth muscle relaxation and vasodilatation, and is an effective treatment for male erectile dysfunction. More than 3.6 million prescriptions have been issued as of August 1998, and so far there have been 69 deaths, 12 of which were attributable to the interaction with nitrates, as reported to the FDA. 

Indications Erectile dysfunction, Hypertension Category Phosphodiesterase type 5 inhibitor Half-life 4 hours... 

---