PDE5 Inhibitor
Quick Definition
A PDE5 inhibitor is a medication that inhibits the enzyme phosphodiesterase type 5, which degrades cyclic guanosine monophosphate (cGMP) in vascular smooth muscle. The class is FDA-approved for erectile dysfunction and pulmonary arterial hypertension, and includes sildenafil, tadalafil, vardenafil, and avanafil.
In Depth
PDE5 inhibitors enhance the natural vasodilatory response to nitric oxide signaling by blocking the enzymatic breakdown of cyclic GMP (cGMP). The class transformed the treatment of erectile dysfunction starting with the FDA approval of sildenafil (Viagra) in 1998.
The mechanism: sexual stimulation produces nitric oxide release in the penile vasculature, which activates guanylate cyclase to produce cGMP. cGMP relaxes vascular smooth muscle, allowing increased blood flow into the corpus cavernosum and producing erection. PDE5 normally breaks down cGMP, terminating the signal. PDE5 inhibitors prolong cGMP signaling, enhancing erectile response.
The four PDE5 inhibitors marketed in the U.S.:
- Sildenafil (Viagra, Revatio). Half-life ~4 hours. Onset 30-60 minutes. Reduced absorption with high-fat meals. - Tadalafil (Cialis). Half-life ~17.5 hours. Onset 30-45 minutes. Food-insensitive. Daily low-dose option. - Vardenafil (Levitra). Profile similar to sildenafil. - Avanafil (Stendra). Faster onset (~15 minutes), shorter half-life. Higher selectivity for PDE5 vs PDE6.
Sildenafil and tadalafil are by far the most commonly prescribed in U.S. practice.
The shared side effect profile includes headache, flushing, nasal congestion, dyspepsia, and visual changes. Tadalafil is more associated with back and muscle pain. Serious but rare risks include priapism, sudden hearing loss, and non-arteritic anterior ischemic optic neuropathy (NAION).
The most important contraindication is concurrent nitrate therapy, which produces dangerous hypotension. Alpha blocker dose-staggering is generally required.
PDE5 inhibitors do not produce erections without sexual stimulation. They amplify the body's natural response.
Related Terms
Tadalafil
Tadalafil is a long-acting PDE5 inhibitor FDA-approved for erectile dysfunction (Cialis) and benign prostatic hyperplasia. Its 17.5-hour half-life produces a 24-36 hour clinical window, supporting both on-demand and daily low-dose dosing schedules.
Sildenafil
Sildenafil is a short-acting PDE5 inhibitor FDA-approved for erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio). Its onset is 30-60 minutes and clinical window is approximately 4 hours, with absorption sensitive to high-fat meals.