Erectile Dysfunction Medications

• Erectile dysfunction (ED), also referred to as impotence, is the inability to attain or maintain an erection sufficient for successful sexual activity.
• Normally, an erection occurs when the arteries carrying blood to the penis widen, allowing more blood to flow in, and the veins carrying blood away from the penis are compressed, restricting blood from flowing out.
• In other words, more blood flows in and less flows out, making the penis larger and causing an erection.
• Certain nerves and hormones in the body also play a role in initiating and maintaining an erection.
• Any abnormality involving the nervous, circulatory or hormonal systems, whether due to medication or disease, may affect the ability to develop and sustain an erection, to ejaculate, and to experience orgasm.

Erectile dysfunction can be caused by any number of physical and psychological factors. In general, erectile dysfunction is classified according to whether it is caused by organic (caused by a bodily organ or organ system) or psychogenic (mental) factors. Diseases, nutritional status, trauma, surgical procedures, or medications can affect erectile function by altering the nervous, vascular, or hormonal systems. Some men have more than one cause for their erectile dysfunction.

In addition to taking medications to treat erectile dysfunction, it is important to make lifestyle changes that may alter the underlying cause of erectile dysfunction. Such changes include improving eating habits, quitting tobacco and alcohol products, and/or getting regular exercise. Some doctors may prescribe more than one medication, depending on a patient's response and ability to tolerate the various medications.

Phosphodiesterase type 5 inhibitors (PDE5) inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis).

• How PDE5 inhibitors work: Following sexual stimulation, PDE5 inhibitors increase blood flow to the penis, causing an erection. Penile erection is caused by the engorgement of the penis with blood. This engorgement occurs when the blood vessels delivering blood to the penis increase the delivery of blood, and the blood vessels carrying blood away from the penis decrease the removal of blood. Under normal conditions, sexual stimulation leads to the production and release of nitric oxide in the penis. Nitric oxide then activates the enzyme, guanylate cyclase, which causes the production of cyclic guanosine monophosphate (cGMP). It is the cGMP that is primarily responsible for the erection by affecting the amount of blood that the blood vessels deliver and remove from the penis. PDE5 inhibitors inhibit an enzyme called phosphodiesterase-5 (PDE5), which destroys the cGMP. Thus, PDE5 inhibitors prevent the destruction of cGMP and allow cGMP to accumulate and persist longer. The longer cGMP persists, the more prolonged the engorgement of the penis.
• Who should not use these medications: Persons with allergy to PDE5 inhibitors should not use them. Concurrent use of nitrate medications (for example, nitroglycerin [Nitro-Bid, Nitro-DUR, Nitroderm, Nitrogard, Nitrolingual, Nitrostat], isosorbide mononitrate [ISMO], or isosorbide dinitrate [Isordil, ISDN, Sorbitrate]) increases the potential for excessively low blood pressure. Taking nitrates is an absolute contraindication to the use of these medicines. PDE5 inhibitors should not be used by individuals who are taking nitrates.
• Use: The prescribed tablet strength is swallowed 15-60 minutes before sexual activity. Sildenafil (Viagra) and vardenafil (Levitra) work best if taken without having eaten food within the last 2 hours. Tadalafil (Cialis) may be taken without regard to food. Tadalafil (Cialis) has a longer duration of action (up to 24-36 h) compared with Sildenafil (Viagra) and vardenafil (Levitra) (up to 4-12 h). Tadalafil (Cialis) 2.5-5 mg may be administered daily without regard to sexual activity.
• Drug or food interactions: Some drugs that may increase PDE5 inhibitors’ effect include erythromycin (E-Mycin, Ery-Tab), ketoconazole (Nizoral), itraconazole (Sporanox), indinavir (Crixivan), and ritonavir (Norvir). When PDE5 inhibitors are given to men taking nitrate medications (see above), excessively low blood pressure may occur. Low blood pressure has also been shown to occur when PDE5 inhibitors are taken with other drugs that lower blood pressure, such as terazosin (Hytrin), doxazosin (Cardura), prazosin (Minipress), alfuzosin (Uroxatral), or tamsulosin (Flomax).
• Side effects: Common adverse effects include headache, flushing, runny nose, stomach pain, back pain (Cialis),and indigestion. Lower doses are used for individuals with liver and/or kidney disease. PDE5 inhibitors may cause dizziness or a sudden drop in blood pressure. Men with heart disease require a doctor's evaluation before they begin use of PDE5 inhibitors and, possibly, may need lower PDE5 doses. Some men (<2%) experience prolonged or painful erections. Visual problems (for example, blurred vision, increased sensitivity to light, bluish haze, or temporary difficulty distinguishing between blue and green) may occur.

Androgens include testosterone (Depo-Testosterone, Delatest, Andro-L.A., AndroGel, Testim, Androderm, Axiron, Fortesta, Striant, Testopel, Testoderm).

• How androgens work: Androgens are hormones that affect normal growth and development of male sex organs and maintenance of secondary sexual characteristics, including the growth and maturation of the prostate, seminal vesicles, penis, and scrotum. Beard, pubic hair, chest hair, axillary hair, deepening of voice, and alterations in body musculature also are controlled by androgens. Testosterone may be beneficial in men with low sexual desire. Sexual desire and an overall sense of well-being are likely to improve when serum testosterone levels (blood levels) are restored to normal concentrations. Doctors will periodically check the testosterone blood level to see if it improves.
• Who should not use these medications: Men with prostate cancer or allergy to testosterone should not take them, nor should men with severe heart or kidney disease, benign prostatic hypertrophy with obstruction, breast cancer, or unexplained genital bleeding. Men taking androgens need to obtain semiannual blood tests, including prostate specific antigen (PSA), liver function tests, and a complete blood count.
• Use: Testosterone is available in a variety of forms including oral (tablets or capsules), injections, topical patches, ointments, and gels.
• Drug or food interactions: These medications may increase the effect of anticoagulants (blood thinners) such as warfarin (Coumadin).
• Side effects: Testosterone may worsen low blood sugar levels, raise red blood cell count (erythrocytosis) or increase blood pressure. Topical application may cause skin irritation. Rare side effects include headache, insomnia, or mood swings. Pain at the injection site is not uncommon.

Prostaglandins include alprostadil (Caverject, Edex, Muse Pellet).

• How prostaglandins work: These drugs work by enhancing blood flow to the penis, thereby causing erection. Alprostadil (Caverject, Edex, Muse Pellet) is a naturally occurring prostaglandin E1 synthetically manufactured for commercial use. Alprostadil is a vasodilator that induces erection by relaxing smooth muscle and widening arteries that supply blood to the penis. Increased blood supply to the penis facilitates erection.
• Who should not use these medications: Persons with allergy to alprostadil should not take them, nor should persons with hyaline membrane disease, respiratory distress syndrome, penile implants or an abnormally formed penis, or conditions resulting in long-lasting erections (for example, sickle cell anemia or trait, leukemia, or multiple myeloma).
• Use: Prostaglandins are administered as either an injection into the penis or as a pellet inserted into it (via the urethral opening at the end of the penis).
• Drug or food interactions: No drug or food interactions are currently known.
• Side effects: A prolonged erection lasting more than four hours may occur, and if this occurs a physician should be contacted. Prostaglandins may cause headache, decreased blood pressure, or dizziness. Caution is warranted in individuals with heart disease that may be aggravated by decreased blood pressure.

Phentolamine and papaverine injection: These medications have been prescribed for many years and are very effective and inexpensive. Both of these drugs are used for other diseases, but the US Food and Drug Administration has not formally approved them for treating erectile dysfunction. Prostaglandin, phentolamine, and papverine are often combined and prescribed as Trimix.

The following drugs are currently undergoing investigation for use in treating erectile dysfunction:

• Phentolamine (Regitine) and papaverine (Genabid, Pavabid, Pavatine) injection: This therapy has been prescribed for many years. Both of these drugs are used for other diseases, but the US Food and Drug Administration has not formally approved them for treating erectile dysfunction. Phentolamine has recently been in short supply, and the introduction of newer, effective drug therapy has limited use of this combination.
• Apomorphine (Uprima)
• PT-141 (a melanocortin receptor activator given as a nasal spray)
• Alprostadil cream (Alprox-TD)