Erectile Dysfunction - Intracavernous Injection

One of the most dramatic changes in urology has been the introduction of intracavernous injection of vasoactive drugs for the diagnosis and treatment of ED. A list of drugs that have been used clinically is presented in Table 37-5.

A. Papaverine

Papaverine is an alkaloid isolated from the opium poppy. Its molecular mechanism of action is through its inhibitory effect on phosphodiesterase, leading to increased cAMP and cGMP in penile erectile tissue and thus relaxing cavernous smooth muscle and penile vessels. Papaverine is metabolized in the liver, and the plasma half-life is about 1-2 h.

The average dose for papaverine injection ranges from 15 to 60 mg. Papaverine has been shown to be effective in psychogenic and neurogenic ED (Virag, 1982). The advantages are its low cost and stability at room temperature. The major disadvantages are the higher incidence of corporal fibrosis (1-33%), thought to be a result of low acidity (pH 3-4), and occasional elevation of liver enzymes.

B. Phentolamine Methylate (Regitine)

Phentolamine methylate is a competitive alpha-adrenoceptor antagonist with equal affinity for alpha-1 and alpha-2 receptors. Systemic hypotension, reflex tachycardia, nasal congestion, and gastrointestinal upset are the most common systemic side effects. It has a short plasma half-life (30 min). When injected intracorporally alone, it increases corporal blood flow but does not result in a significant rise in intracorporal pressure.

C. Alprostadil (Prostaglandin E1)

Alprostadil is the synthetic form of a naturally occurring unsaturated 20-carbon fatty acid (ie, alprostadil refers to the exogenous form; prostaglandin E1 to the endogenous compound). It causes smooth-muscle relaxation, vasodilation, and inhibition of platelet aggregation through elevation of intracellular cAMP. Alprostadil is metabolized by the enzyme prostaglandin 15-hydroxydehydrogenase, which has been shown to be active in human corpus cavernosum (_{Roy et al, 1989}). After intracavernous injection, 96% of alprostadil is locally metabolized within 60 min and no change in peripheral blood levels has been observed (_{van Ahlen et al, 1994}).

In the United States, 2 formulations of alprostadil have been approved by the FDA for intracavernous therapy: Caverject (_{Pharmacia & Upjohn, Peapack, NJ}) and Edex (_{Schwarz Pharma, Milwaukee, WI}). Caverject is a lyophilized alprostadil powder developed for intracavernous injection. Edex is lyophilized alprostadil contained in an alpha cyclodextrin inclusion complex.

At a dosage of 10-20 ug, alprostadil produced full erections in 70-80% of patients with ED (). The most frequent side effects were pain at the injection site or during erection (occurring in 16.8% of patients), hematoma/ecchymosis (1.5%), and prolonged erection/priapism (1.3%). Systemic side effects occurred rarely ().