Erectile Dysfunction and Hypertension

R Kloner

Disclosures

Int J Impot Res. 2007;19(3):296-302. 

In This Article

The Nitrate Contraindication

All three PDE5 inhibitors are contraindicated in patients taking organic nitrates (including short-acting or long-acting nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, amyl nitrate and others). Organic nitrates increase cyclic GMP production whereas PDE5 inhibitors decrease cyclic GMP breakdown. Therefore, there is a synergistic drop in BP when PDE5 inhibitors are given with organic nitrates that results in symptomatic hypotension in some patients.[11,12,13,15,16]

If a patient has taken a PDE5 inhibitor and then develops chest pain, when is it safe to re-introduce nitroglycerin? The original American College of Cardiology/American Heart Association guidelines suggested that for sildenafil, 5-6 half-lines or 24 h pass before nitrates are given to a patient who has taken sildenafil (half-life is about 4 h).[28] Studies comparing nitrate interaction between sildenafil versus tadalafil confirmed that there was a lack of interaction between sildenafil and nitrate 24 h after sildenafil was administered.[15] There is an unpublished study suggesting a lack of interaction with nitroglycerin at 24 h after vardenafil, consistent with its 4 h half-life.[13] Finally, one study suggests an interaction between tadalafil (half-life 17.5 h) and nitroglycerin that is present at 24 h after a dose of tadalafil but that is gone by 48 h and beyond.[29]

Thus, although all three PDE5 inhibitors are contraindicated in patients receiving either short-acting or long-acting nitrates, should a patient with ED take a PDE5 inhibitor and then develop angina, nitroglycerin should not be reintroduced until after 24 h for sildenafil or vardenafil and after 48 h for tadalafil. Of course, other antianginal and anti-ischemic therapies may be used - such as beta blockers, calcium blockers, aspirin, morphine, statins and percutaneous coronary intervention. None of these are contraindicated with PDE5 inhibitors. The American College of Cardiology/American Heart Association Guidelines address the approach to the patient who has developed hypotension in the setting of PDE5 inhibitors plus nitrates.[28]

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