A calcium sensitiser used in the management of acutely decompensated congestive heart failure.
Trade name Simdax.
Routes of administration IV
Protein binding 97–98%.
Has extensive hepatic metabolism.
Elimination half-life about 1 hour and 75–80 hours for metabolites.
Excretion urine (54%), feces (44%).
Mechanism of action Edit
As a calcium sensitizer, it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium.
It exerts a positive inotropic effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner.
It has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.
The combination of inotropic and vasodilatory actions result in an increased force of contraction, decreased preload and decreased afterload.
It opens also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, exerting a cardioprotective effect.
It is indicated for inotropic support in acutely-decompensated severe congestive heart failure in situations where conventional therapy is not adequate.
In the SURVIVE study, there was a reduction in plasma B-type natriuretic peptide levels, but did not significantly reduce all-cause mortality at 180 days.
It is superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations.
Its use is contraindicated in patients with moderate-to-severe kidney impairment, severe liver impairment, severe ventricular filling or outflow obstruction, very low blood pressure and fast heart rate, and/or history of the abnormal heart rhythm torsades de pointes.
Adverse effects: headache, hypotension, arrhythmias, myocardial ischemia, hypokalaemia and/or nausea.
It is marketed as a 2.5 mg/mL concentrated solution for IV infusion, that is diluted with glucose 5% solution before infusion.