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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Urology

      Erectile Dysfunction Medication

      Updated: Jul 19, 2022
      • Author: Edward David Kim, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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      Medication

      Medication Summary

      A growing array of medications is available to assist in the management of erectile dysfunction (ED). An ideal agent would be rapidly effective, easy to administer, affordable, applicable to a wide range of patients, and minimally toxic. The types of medications can be divided into oral, topical, injectable, and intraurethrally inserted. Phosphodiesterase type 5 (PDE5) inhibitors are the principal oral agents used in ED.

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      Phosphodiesterase-5 Enzyme Inhibitors

      Class Summary

      At least seven phosphodiesterase (PDE) classes are known, many with subtypes identified by structure and function. PDEs are a diverse family of enzymes that have different tissue distributions and functions but that all exert their effect by lowering intracellular levels of cyclic nucleotides, such as cyclic guanosine monophosphate (cGMP).

      PDE5 is cGMP-specific and is a major cGMP-hydrolyzing enzyme in the vascular smooth muscle of the penis. PDE5 inhibitors rely on the role of nitric oxide (NO) in inducing vasodilatation. NO relaxes the smooth muscle of the corpora cavernosa peripherally by stimulating guanylyl cyclase activity, which results in increased cGMP levels; inhibition of PDE5 increases intracellular concentrations of cGMP, which, in turn, induces vasodilation.

      Available PDE5 inhibitors include sildenafil, vardenafil, tadalafil, and avanafil. These agents do not directly cause penile erections but affect instead the response to sexual stimulation. Sildenafil was the first to be approved, avanafil the most recent. Although all of these agents inhibit PDE5, the newer drugs in the class are significantly more selective in their inhibition.

      Sildenafil (Viagra)

      Sildenafil is most effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response. Sildenafil is available as 25-, 50-, and 100-mg tablets.

      Vardenafil (Levitra, Staxyn)

      Vardenafil is most effective in men with mild-to-moderate ED. It is to be taken on an empty stomach approximately 1 hour before sexual activity. Sexual stimulation is necessary to activate response. Vardenafil is available as 2.5-, 5-, 10-, and 20-mg tablets.

      Tadalafil (Cialis)

      Tadalafil is a PDE5-selective inhibitor that is chemically unrelated to sildenafil and vardenafil. It is most effective for mild-to-moderate ED of varying etiologies, including both organic and psychogenic causes. May take 30 min prior to sexual activity.

      Increased sensitivity for erections may last 36 hours with intermittent dosing. Low-dose daily dosing may be recommended for more frequent sexual activity (eg, twice weekly); men can attempt sexual activity at any time between daily doses. In 2011, tadalafil was also FDA approved for daily use for the treatment of men with BPH, as well as ED.

      Tadalafil is available as 2.5-, 5-, 10-, and 20-mg tablets. In patients who respond, coitus has been recorded from 30 minutes to 36 hours after administration.

      Avanafil (Stendra)

      Avanafil is a PDE5 inhibitor that inhibits cGMP degradation and thereby enhances the effects of NO in smooth muscle relaxation of the corpus cavernosum. May take 30 min prior to sexual activity.

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      Vasodilators

      Class Summary

      Some agents injected directly into the penis exert their relaxant effect directly on the smooth muscle of the corpora cavernosa. They can be used alone or in combination with other medications. The most commonly used agents are alprostadil (prostaglandin E1 [PGE1]), papaverine, and phentolamine. The optimal dosages and the most effective combination of these agents must be determined on a case-by-case basis.

      These medications can be obtained as commercial preparations or can be formulated according to the physician’s request by compounding pharmacies. Patients can be supplied with vials of a single agent or a combination of agents mixed in a single vial. Patients must be instructed in the proper technique for administration.

      A single intraurethral agent, PGE1, which has been formulated into a small suppository, is commercially available as a component of the Medicated Urethral System for Erections (MUSE). This agent was available before the introduction of sildenafil and is still used by a select group of men.

      Alprostadil (Caverject, Caverject Impulse, Edex, Muse)

      Alprostadil is identical to naturally occurring PGE1 and has various pharmacologic effects, including vasodilation and inhibition of platelet aggregation. When injected into the penile shaft, it relaxes trabecular smooth muscle and dilates cavernosal arteries, thereby, in turn, promoting blood flow and entrapment in the lacunar spaces of the penis, causing penile erection. Various doses have been employed.

      Papaverine

      Papaverine is a benzylisoquinoline derivative with a direct nonspecific relaxant effect on vascular, cardiac, and other smooth muscles. In the treatment of erectile dysfunction, it is injected intracavernosally into the penis to increase blood flow to the penis and produce an erection.

      Phentolamine

      Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine, reducing the hypertension that results from catecholamine effects on the alpha-receptors. Injected into the penis, it causes an erection.

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      Androgens

      Class Summary

      Androgens are primarily of benefit in men with low levels of serum testosterone (hypogonadism). Men with hypogonadism who desire a restoration of libido and who wish to become sexually active usually benefit from exogenous supplementation of androgens. This can be accomplished with injections, cutaneous application via gel or skin patches, or oral administration.

      Testosterone (AndroGel, Axiron, Depo-Testosterone, Testopel, Testim, Androderm, Striant, Fortesta, Natesto, Aveed)

      Testosterone promotes and maintains secondary sex characteristics in androgen-deficient males. Depot injections can produce high levels of serum testosterone when administered in adequate doses. Because of its adverse effects, the use of testosterone replacement therapy is limited to men with testosterone levels less than 300 ng/dL.

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