CURRENT TREATMENTS FOR ERECTILE DYSFUNCTION
The term impotence has usually been employed to indicate the inability of the male to attain and maintain erection of the penis sufficient to permit satisfactory sexual intercourse. The preferred term is now erectile dysfunction (ED). ED is a common problem, especially among older men. In the U.S. alone, approximately 10 million men suffer from ED. According to the National Center for Health Statistics (1989), ED results in nearly a half-million outpatient visits. While erectile function may not be the most important indicator of sexual satisfaction, ED may contribute to mental stress that affects interactions with family and associates.
A comprehensive review of the pharmacology of various agents used in the treatment of ED reveals a continuing emergence of knowledge about their mechanism(s) of action and their clinical efficacy. Both systemic and locally-active agents are available. Their site(s) of action may be peripheral or central acting. Sometimes, a combination of agents is effective, but often this is determined by the etiology of the ED. Significant insight has been gained in the last decade with respect to the pharmacologic action of drugs used in the treatment of ED.
Viagra is available as an oral tablet ranging from 25 to 100 Mg. A starting dose of 50 Mg taken about one hour prior to sexual intercourse has been recommended. Viagra has been reported as a safe and efficacious treatment for ED, however, it is ineffective in approximately 27 to 35% of the population and has been associated with a variety of adverse effects including headache, flushing, dyspepsia, and adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. Viagra should not be taken in conjunction with nitrate therapy.
While testosterone can enhance male sexual function, testosterone therapy for the treatment of ED should be discouraged unless the etiology is clearly related to low testosterone levels. Testosterone therapy in men with normal levels may enhance sexual behavior, but is without significant effects upon erectile function. Transdermal patches (e.g., Testoderm, Androderm) and topical testosterone gel (e.g., Androgel) are commercially available. Improvements following testosterone (transdermal) may require several months of therapy. Transdermal delivery systems may provide better consistency in serum testosterone than injections, but are perhaps more expensive. There is always the chance of the patches falling off while showering or skin irritations, which require removal of the patches.
Alprostadil binds with PGE receptors, and the resultant relaxation response in the smooth muscle is mediated by cAMP. Little is known about the pharmacokinetics of PGE1 but it is believed that as much as 80% may be metabolized in one pass through the lungs. In all probability, this rapid degradation by the lungs accounts for its lack of any significant cardiovascular system side-effects when administered intracavernosally. It can also be metabolized in the penis. Alprostadil has also been used in combination with other agents, such as papaverine, and the combination was superior to only alprostadil. Alprostadil is available as a transurethral system (Muse), a topical cream with penetration enhancers, or intracavernosal injection. One study showed that the injection is more efficacious. It is effective therapy with tolerable side-effects.
Apomorphine, along with sildenafil, is one of the few orally active pharmacological agents used in the treatment ED. Several studies have demonstrated that apomorphine stimulates erection in humans. In particular, apomorphine can induce penile erection in normal men, in men that are impotent, and in alcoholics. Apomorphine has been used to treat ED In patients with co-existing benign prostatic hyperplasia (BPH), with coronary artery disease, and with hypertension. When formulated into a controlled release sublingual tablet, it becomes a very effective orally active drug. Durable erections without side-effects can be attained at a dose range of 3 to 4 mg.
Papaverine is particularly known as a smooth muscle relaxant and vasodilator. Its principle pharmacological action is as a non-specific vasdilator of the arterioles and capillaries. Papaverine dosages may range from 15 to 60 Mg. Major side-effects include priapism and corporeal fibrosis. Intra-corporeal scarring may be related to the low pH which is necessary in order to solubilize the drug. These side-effects are greatly reduced when papaverine is used in very low dosages combined with phentolamine and alprostadil.
Phentolamine may provoke a reflex, increasing sympathetic outflow and release of norepinephrine. When phentolamine is used for the treatment of ED, it is often used in combination with other agents (e.g. papaverine) to enhance its efficacy. The combination of phentolamine and papaverine for the treatment of ED has been studied extensively. This combination can be efficacious and may induce erections sufficient for sexual intercourse in over 90% of cases. Phentolamine has been used orally and intracavernosally. It has also been shown to be effective buccally.
Forskolin As reported in the Journal of Urology, 1997 Nov;158(5):1752-8; discussion 1758-9, the drug called forskolin, has demonstrated safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent (phentolamine/papaverine/prostaglandin E1) pharmacotherapy. Forskolin acts synergistically with prostaglandin E1 to produce improvement in rigidity and/or erection duration with no adverse events. If you would like more information in forskolin, please call and ask for Neil, Scott or Tuan.
Urology 2000 Oct 1;56(4):647-52
Three-year outcome of a progressive treatment program for erectile dysfunction with intracavernous injections of vasoactive drugs.
Baniel J, Isarailov S, Engelstein D, Shmueli J, Segenreich E, Livne PM.
Institute of Urology, Rabin Medical Center, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
OBJECTIVES: To perform a comparative evaluation and follow-up of patients with erectile dysfunction (ED) who were treated with intracavernous injection of vasoactive drugs, starting with simple drugs and advancing to complex combinations.