Phosphodiesterase-5 inhibitors therapy in patients treated with nitrates

Abstract

More than 1.5 million men in Poland suffer from erectile dysfunction and 60% of them are aged between 40–60 years. Orally administered selective and reversible phosphodiesterase type 5 inhibitors (PDE-5) are the first choice treatment of erectile dysfunction. Currently, there are three drugs in this class: sildenafil (Viagra) and vardenafil (Levitra) - the first generation, short acting PDE-5 inhibitors with 4-6 hours efficacy; and one representative of second generation: tadalafil (Cialis), differentiated from others by high efficacy maintained throughout minimum 24 hours. The mode of action of all the drugs is identical. Selective PDE-5 inhibitors are contraindicated in patients treated with nitrates, as combination of these treatments results in significant decreases of blood pressure and reflex tachycardia. The synergistic action of combined nitrates - PDE-5 inhibitors therapy results from the accumulation of second messenger - cGMP. Nitrates increase the concentration of egzogenic nitric oxide (NO) and stimulate the production of the second messenger - cGMP. Selective PDE-5 inhibitors inhibit action of PDE-5 enzyme and increase the concentration of cGMP. Combined synergistic action of those two drugs leads to increased concentration of cGMP in vessel walls and decreased vessel resistance and blood pressure. Nitrates may be administered not earlier than at least 24 hours post PDE-5 inhibitor tablet usage. Also PDE-5 inhibitors should not be used earlier than 24 hours following last dose of nitrates. In case of long acting nitrates the usage should be postponed for further 24 hours.