Simendan
Simendan - General Information
Simendan is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Simendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.
Pharmacology of Simendan
Simendan is a new Ca2+-sensitizing inotropic agent. Ca2+ sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca2+ overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Simendan has not been approved for use in the U.S. or Canada.
Simendan for patients
Simendan Interactions
No Important Interactions To Date
Levosimendan does not have clinically important pharmacokinetic interactions with captopril, beta-blockers, felodipine, digoxin, warfarin, isosorbide mononitrate, carvedilol, ethanol or itraconazole.
Simendan Contraindications
The use of levosimendan is contraindicated in patients with: moderate-to-severe renal impairment, severe hepatic impairment, severe ventricular filling or outflow obstruction, severe hypotension and tachycardia, and/or history of torsades de pointes.
Additional information about Simendan
Simendan Indication: For short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease.
Mechanism Of Action: Simendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, thereby (1) changing actin-myosin cross-bridge kinetics apparently without increasing the cycling rate of the cross-bridges or myocardial ATP consumption, (2) increasing the effects of calcium on cardiac myofilaments during systole and (3) improving contraction at low energy cost. Calcium concentration and, therefore, sensitization decline during diastole, allowing normal or improved diastolic relaxation. Simendan also leads to vasodilation through the opening of ATP-sensitive potassium channels. By these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand. Simendan also has a selective phosphodiesterase (PDE)-III inhibitory action that may contribute to the inotropic effect of this compound under certain experimental conditions. It has been reported that levosimendan may act preferentially as a Ca2+ sensitizer at lower concentrations, whereas at higher concentrations its action as a PDE-III inhibitor becomes more prominent in experimental animals and humans.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Levosimendan
Synonyms: Levosimedan
Drug Category: Anti-Arrhythmia Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Vasodilator Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Levosimendan: Simendan; Simdax;
Absorption: The bioavailability of oral levosimendan is 85 ± 6% in healthy volunteers and 84 ± 4% in patients.
Toxicity (Overdose): Not Available
Protein Binding: 98% bound to plasma protein.
Biotransformation: Complete metabolism, with some active metabolites (OR-1855 and OR-1896) possibly extending the drug's haemodynamic effects.
Half Life: Eliminination half-life is approximately 1 hour.
Dosage Forms of Simendan: Not Available
Chemical IUPAC Name: 2-[[4-[(4R)-4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl]phenyl]hydrazinylidene]propanedinitrile
Chemical Formula: C14H12N6O
Levosimendan on Wikipedia: https://en.wikipedia.org/wiki/Levosimendan
Organisms Affected: Humans and other mammals
