Phosphodiesterase inhibitors

Depending on the phosphodiesterase at which the inhibitors are targeted, there are different effects:

• PDE3 inhibitors (such as amrinone, milrenone and enoximone) are used in the short-term treatment of severe acute myocardial insufficiency. However, they frequently trigger cardiac arrhythmia and are only used in special emergency situations. Due to the many and severe undesirable side effects, they are not suitable for long-term treatment.
• Inhibitors of PDE5 (sildenafil, tadalafil, vardenafil) promote the signal transmission pathway that controls the flow of blood into the erectile tissue of the penis during sexual arousal with the help of the messenger substance cGMP. Under the influence of PDE5 inhibitors, erectile function is strengthened. Under no circumstances should PDE5 inhibitors be taken together with nitro-based vasodilators (risk of a drop in blood pressure and heart attack).
• Inhibition of PDE4 leads to suppression of numerous pro-inflammatory parameters. Various substances are approved for long-term therapy in adults with COPD and chronic bronchitis (e.g. Roflumilast). Indications: bronchial asthma, rheumatoid arthritis, multiple sclerosis. The substance crisaborol has been tested positive in 2% ointment form in 2 clinical phase III trials in atopic eczema (approved for this indication in the USA in 2016).

1. Paller AS et al (2016) Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol 75:494-503.