PDE-5 inhibitors

Phosphodiesterase 5 inhibitors (also phosphodiesterase V inhibitors or PDE 5 inhibitors ) are substances that inhibit the cGMP- degrading enzyme phosphodiesterase V and thus increase the concentration of intracellular cGMP (cyclic guanosine monophosphate). Among other things, they cause blood vessels to widen ( vasodilation ). Phosphodiesterase-5 inhibitors were originally developed for the treatment of angina pectoris and high blood pressure , but are now used in the therapy of erectile dysfunction and in the therapy of pulmonary hypertension . PDE-5 inhibitors require a prescription.

Mechanism of action

Phosphodiesterase 5 inhibitors are inhibitors of phosphodiesterase V, an enzyme from the group of phosphodiesterases. Phosphodiesterases are responsible for the breakdown of the intracellular messenger substances ( second messenger ) cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterase V is able to selectively break down cGMP. For its part, cGMP is the second messenger that is activated by the endothelial relaxation factor nitrogen monoxide (NO) and is thus involved in the relaxation of blood vessels. Since phosphodiesterase 5 inhibitors inhibit the inactivation of cGMP, they lead to an increase in the vasodilating effect of nitric oxide.

The effect of phosphodiesterase 5 inhibitors can be observed in particular in tissues in which phosphodiesterase V occurs mainly. In addition to the smooth muscles of the blood vessels, where phosphodiesterase 5 inhibitors lead to relaxation, this also includes the lung tissue and platelets . Of particular interest to the pharmaceutical industry is the indication of erectile dysfunction , which is based on the relaxing effect on the blood vessels supplying the erectile tissue of the penis and the resulting easier erection . However, PDE-5 inhibitors only work if a sexual stimulus is triggered in the brain , which causes nerve impulses and transmits them to the male reproductive organ. Accordingly, the phosphodiesterase-5 inhibitors act as a link between erection and sexual arousal .

Substances

Due to the selectivity for isoform V of phosphodiesterase, a distinction can be made between non-selective phosphodiesterase inhibitors , such as the methylxanthines caffeine , theophylline , theobromine , which inhibit various non-specific phosphodiesterases and the selective inhibitors of phosphodiesterase V, such as. B. Sildenafil ( Viagra , Revatio , Generika), Tadalafil ( Cialis , Adcirca , Generika), Vardenafil ( Levitra ) and Avanafil ( Spedra , available since April 2014).

interaction

Since phosphodiesterase 5 inhibitors have a vasodilating effect, they can increase the effect of antihypertensive drugs such as calcium channel blockers . In addition, virus inhibitors, antidepressants and antibiotics can influence the enzyme structure of PDE-5 inhibitors and thus their effectiveness. In addition, the anti- epileptic drugs carbamazepine and phenobarbital accelerate the breakdown of sexual enhancers .

Taking nitrates and nitric oxide donors such as molsidomine and amyl nitrite leads to a drop in blood pressure which, in combination with PDE inhibitors , can lead to a life-threatening drop in blood pressure.

literature

• K. Watling (2006): Sigma-RBI Handbook of Receptor Classification and Signal Transduction. 5th ed., Sigma-RBI, pp. 30-31

Individual evidence

1. ↑ JD Corbin: Mechanisms of action of PDE5 inhibition in erectile dysfunction . In: International Journal of Impotence Research . tape 16 , S1, 2004, pp. S4-S7 , doi : 10.1038 / sj.ijir.3901205 .
2. ↑ Chelsea N. McMahon, Christopher J. Smith, Ridwan Shabsigh: Treating erectile dysfunction when PDE5 inhibitors fail . In: BMJ . tape 332 , no. 7541 , March 2006, p. 589-592 , doi : 10.1136 / bmj.332.7541.589 , PMC 1397768 (free full text).
3. ^ European public assessment report (EPAR) for Spedra - Avanafil (English) , website of the European Health Authority (EMA), accessed on February 21, 2014.
4. ↑ Summary of the EPAR for the public (German) , website of the European Health Authority (EMA), accessed on February 21, 2014 (PDF; 81 kB).
5. ^ Erectile dysfunction - new PDE5 inhibitor avanafil , from the website of the Deutsche Apotheker Zeitung (DAZ), accessed on February 21, 2014.

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