Levosimendan
C01CX08
Calcium sensitizer
Template: Infobox chemical / molecular formula search available
Levosimendan (trade name Simdax ®, Orion Oyj ) is a drug from the group of calcium sensitizer, which is used in the short-term treatment of acute decompensated, severe chronic heart failure.
- 2.1 Mechanism of action ( pharmacodynamics )
- 2.2 pharmacokinetics
Clinical information
Areas of application (indications )
Levosimendan is indicated for short-term treatment of acute decompensated, severe chronic heart failure (English: acutely decompensated severe chronic heart failure, ADHF ) in situations where conventional therapy with intravenous diuretics is not sufficient and a therapy with inotropic agents considers appropriate.
Posology and method of administration
Levosimendan is an infusion concentrate which must be diluted before application. It is only for use in hospital and requires the presence of adequate monitoring equipment as well as experience in therapy with inotropes advance. The dose and the treatment duration can be individually, according to the clinical condition of the patient, and his response to treatment to adjust.
Contraindications ( contraindications)
Levosimendan may not be used in:
- Severe hypotension (low blood pressure )
- Heart rate (tachycardia )
- Significant mechanical disabilities affecting the ventricular filling, the ventricular outflow, or both (e.g., aortic stenosis)
- Severely impaired liver or kidney function
- Torsades de pointes
Adverse effects (side effects)
The most common side effects abnormally fast heartbeat, low blood pressure and headache were observed. Often, insomnia, dizziness, gastrointestinal disturbances (nausea, vomiting, constipation, diarrhea) and decreased potassium and hemoglobin values occurred.
Pharmacological properties
Levosimendan increases the pumping power of the heart (positive inotropic effect ) and widens the blood vessels ( vasodilation effect). The blood flow to the cardiac muscle is improved, without the more oxygen is consumed.
Mechanism of action ( pharmacodynamics )
Levosimendan increases the calcium sensitivity of contractile proteins is caused by binding to the cardiac troponin C. Thus, it increases the contractility (positive inotropic action ), but does not affect the ventricular relaxation ( lusitropy ), which is due to the fact that is the transmembrane flux of calcium is not increased pharmacological relevant concentrations also. For certain patients could even be detected by a positive lusitropy levosimendan, which is possibly due to the fact that levosimendan only in the calcium-rich phase of systole binds to troponin C and in the low-calcium diastole dissolves again and has no effect. In addition, adenosine triphosphate opens levosimendan (ATP) - sensitive potassium channels in vascular smooth muscle, causing the vascular resistance in the coronary arteries is reduced, and in the systemic ( arterial and venous ), vessels ( vasodilatory effect). The preload and afterload of the heart is reduced.
Thus Levosimendan belongs to the group of Inodilatoren.
Pharmacokinetics
Levosimendan is almost completely metabolized in the liver, 54 % of the dose is excreted via the kidneys and 44% in the faeces. The half-life is around 1 hour. The following discontinuation of levosimendan for about 7 to 9 days lasting hemodynamic effect on the metabolite (OR - 1855 and OR -1896 ) due, have half-lives of 70 to 80 hours.
Other Information
Levosimendan was approved in 2000 in Sweden as the world's first country, followed in 2001 by the approval in other European countries. Levosimendan has been developed by the Finnish company Orion.