PDE-3 inhibitors

Phosphodiesterase-3 inhibitors are a subgroup of drugs from the group of phosphodiesterase inhibitors that are approved for the treatment of acute heart failure in the absence of catecholamine response by down-regulating the receptors on the myocardium .

Medicinal substances approved to date are amrinone , cilostazol , milrinone and enoximon . The active ingredient pimobendan is approved for use on dogs .

indication

Treatment of acute heart failure and cardiac shock.

history

The first PDE-3 inhibitor to be discovered was amrinone . Its pharmacological properties were first documented in 1978 by Alfred Emil Farah and Adawia Alousi . In 1983 Ronald E. Weishaar was able to demonstrate the described mechanism of action. From 1984 Amrinon was sold on the German market under the trade name "Wincoram". Successors in 1990 were the imidazole derivative enoximony (“Perfan”) and, as a second generation PDE III inhibitor of the bipyridine type, in July 1993, Milrinon (“Corotrop”) .

Mechanism of action

By inhibiting phosphodiesterase-3 , the second messenger cAMP is increased . This activates protein kinases and phosphorylates calcium channels , whereby the calcium inward current increases during the plateau phase of the action potential and more calcium is released from the sarcoplasmic reticulum . The effect in the heart muscle is positive inotropic, that is, the contraction force ( inotropy ) of the heart muscle is increased. In addition, the uptake of calcium in intracellular stores ( sarcoplasmic reticulum ) is accelerated. The PDE-3 inhibitors also have a positive lusitropic effect, that is, they increase the relaxation rate and facilitate muscle relaxation. They also have a vasodilatory effect and thus belong to the group of inodilators .

Side effects

Reversible thrombopenia , increase in transaminases , arrhythmias

Duration of use

Since the effects gradually weaken and there is also an unexplained increase in mortality in patients with heart failure, PDE-3 inhibitors are only approved for short-term use (no longer than 14 days).

literature

Forth , Henschler, Rummel, General and Special Pharmacology and Toxicology, Munich 2002, page 457
Thiel, Roewer, Anaesthesiologische Pharmakotherapie, Stuttgart 2009, page 285f.
DGAI / DGTHT: Intensive medical care for cardiac surgery patients. - Hemodynamic monitoring and cardiovascular therapy. In: www.awmf.org. Working Group of the Scientific Medical Associations (AWMF), April 1, 2010, accessed on February 12, 2011 .
Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , pp. 50-54.

Individual evidence

↑ Reinhard Larsen (1999), pp. 52-54.
^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 978-3-8047-2113-5 , pp. 177 .

[1] Reinhard Larsen (1999), pp. 52-54.

[2] Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 978-3-8047-2113-5 , pp. 177 .