Phentolamine intracavernosal

Intracavernosal alprostadil has been used successfully in combination with VEDs or vasoactive agents (e.g., papaverine, phentolamine, atropine) that act by different mechanisms. Phosphodiesterase inhibitors should not be added to intracavernosal alprostadil because the combination can cause prolonged erections and priapism. 

Examples of other agents include trazodone (50 to 200 mg/day), yohimbine (5.4 mg three times daily), papaverine (7.5 to 60 mg [single agent therapy] or 0.5 to 20 mg [combination therapy] intracavernosal injection), and phentolamine (1 mg [combination therapy] intracavernosal injection). 

Intracavernosal injection or urethral suppository therapy with alprostadil (PGE1) is a second-line treatment for erectile dysfunction. Doses of 2.5-25 meg are used. Penile pain is a frequent side effect, which may be related to the algesic effects of PGE derivatives however, only a few patients discontinue the use because of pain. Prolonged erection and priapism are side effects that occur in less than 4% of patients and are minimized by careful titration to the minimal effective dose. When given by injection, alprostadil may be used as monotherapy or in combination with either papaverine or phentolamine. 

Phentolamine has been used in the treatment of pheochromocytoma—especially intraoperatively— as well as for male erectile dysfunction by injection intracavernosally and when taken orally (see below). 

The vasoactive amines phentolamine and papaverine are occasionally used as intracavernosal therapy, usually in combination with alprostadil, although their use for erectile dysfunction is off-label. Moxisylyte is another vasoactive agent used as intracavernosal therapy. The drug is approved in several European countries, but is not approved in the United States. The advantages over alprostadil are that with moxisylyte, sexual stimulation is still required to achieve full erection and that detumescence occurs on ejaculation. 

Papaverine is not FDA approved for erectile dysfunction. Intracavernosal papaverine alone is not commonly used for management of erectile dysfunction because large doses are required, and these produce dose-related adverse effects priapism, corporal fibrosis, hypotension, and hepatotoxicity. Papaverine is more often administered in lower doses combined with phentolamine and/or alprostadil. A variety of formulae have been used, but no one mixture has been proven better than other mixtures (see Table 81-6). Combination formulations are considered to be safer and associated with the potential for fewer serious adverse effects than high doses of any one of these agents. ... 

Phentolamine has most often been administered as an intracavernosal injection. Monotherapy is avoided, as large doses are required for an erection, and at these doses systemic hypotensive adverse effects would be prevalent. Most often, phentolamine has been used in combination with other vasoactive agents for intracavernosal administration. A ratio of 30 mg papaverine to 0.5 to 1 mg phentolamine is typical, and the usual dose ranges from 0.1 mL to 1 mL of the mixture. Such a mixture promotes local effects of phentolamine and minimizes systemic hypotensive adverse effects (see Table 81-6). ... 

Hypotension is the most common adverse effect of intracavernosal phentolamine. It is more common and more severe with large doses or in patients with poor injection technique who have injected into a vein (rather than the cavernosa). Prolonged erections have also been reported in patients who used excessive doses of combination intracavernosal therapy. 

Phentolamine is used in combination with papaverine, by intracavernosal injection, to facilitate erections in men with impotence (see Papaverine above). Its mechanism of action is as an a-adrenergic antagonist (see Chapter 13) of both ai- and a2-receptors, causing vasodilation and reduction in peripheral resistance. When administered by intracavernosal injection, it is thought to cause relaxation of the cavernous smooth muscles and vasodilation of the penile arteries. This results in increased arterial... 

There appear to be no published reports of adverse interactions between intracavemous alprostadil (prostaglandin E,) and other drugs used for erectile dysfunction, but some manufacturers say that smooth muscle re-laxants such as papaverine and other drugs used to induce erections such as alpha-blocking drugs [e.g. intracavernosal phentolamine] should not be used concurrently because of the risks of priapism (painful prolonged abnormal erection). ... 

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