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Understanding Erectile Dysfunction Medications (cont.)

Phosphodiesterase Type 5 Inhibitors

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 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.

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