| Class | Ino-dilator |
|---|---|
| Chemistry |
Pyridazinone-dinitrile derivative |
| Routes of administration |
IV |
| Absorption |
High oral bioavailability (85%) |
| Solubility |
pKa 6.3, minimally water soluble |
| Distribution |
VOD = 0.3 L/kg; 99% protein-bound |
| Metabolism |
Metabolised mainly by the liver (95% into inactive metabolites, and 5% into OR1896 which has a long half-life and potent activity) |
| Elimination |
Levosimendan itself has a half life of around 1 hour, but OR1896 has a half-life of over 80 hours. |
| Time course of action |
Effect takes ~3 days to develop, and lasts for two-three weeks |
| Target receptor |
Troponin C |
| Mechanism of action |
By binding to troponin C, levosimendan stabilises its open state, allowing muscle contraction. This increases contractility. It also vasodilates by activating ATP-sensitive potassium channels in vascular smooth muscle (like hydralazine). Additionally, at high doses,it acts as a phosphodiesterase (PDE3) inhibitor. |
| Clinical effects |
Increased cardiac contractility, increased heart rate, significant arterial and venous vasodilation (including pulmonary arterial vasodilation), decreased afterload, increased arrhythmogenicity. Purported cardioprotective effect. |
| Literature reference |
Antila et al (2007) |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |