Levosimendan

Levosimendan is a calcium sensitizer – it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its positive inotropic 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. The combined inotropic and vasodilatory actions result in an increased force of contraction, decreased preload and decreased afterload. Moreover, by opening also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, the drug exerts a cardioprotective effect.

Pharmacology

Levosimendan is a calcium sensitizer that enhances the contractility of the heart by increasing the sensitivity of the heart to calcium. It achieves this by binding to cardiac troponin C in a calcium-dependent manner, which results in an increased force of contraction.

In addition to its inotropic effects, levosimendan also has vasodilatory properties. It opens adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle, causing the muscle to relax. This leads to a decrease in preload and afterload, which are the pressures that the heart must work against to pump blood.

Levosimendan also opens mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, providing a cardioprotective effect. This is thought to be due to the preservation of mitochondrial function during periods of metabolic stress, which can help to prevent cell death and reduce the risk of heart failure.

Clinical Use

Levosimendan is used in the management of acute heart failure. It is administered intravenously and has a rapid onset of action, with effects lasting for up to a week after the end of a 24-hour infusion. This makes it particularly useful in patients who require immediate relief from symptoms of heart failure.

Side Effects

Common side effects of levosimendan include headache, dizziness, hypotension, and arrhythmias. These are generally mild and resolve once the drug is discontinued.

Etymology

The name "levosimendan" is derived from the Latin "levo-", meaning "left", and "simendan", a non-standard word possibly derived from the Greek "simi", meaning "force" or "strength". This could be interpreted to mean "left strength", possibly referring to the drug's effects on the left ventricle of the heart.

See Also

• Calcium sensitizer
• Cardiac troponin C
• Acute heart failure

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