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8 - Levosimendan

Published online by Cambridge University Press:  15 December 2009

By
Scott Mercer  and
Andrew Rhodes
Edited by
Jeremy Cashman  and
Michael Grounds
Scott Mercer
Affiliation:
Pharmacy St Thomas' Hospital Lambeth Palace Road London SEI 7EH UK
Andrew Rhodes
Affiliation:
St George's Hospital Blackshaw Road London SW17 0QT UK
Jeremy Cashman
Affiliation:
St George's Hospital, London
Michael Grounds
Affiliation:
St George's Hospital, London
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Summary

Calcium sensitisers are a new class of positive inotropic drugs that are potentially useful in the treatment of acute decompensated heart failure. They have a unique mechanism of action that differs from other available intravenous agents such as dobutamine, a β-agonist, and milrinone, a phosphodiesterase inhibitor. Unlike dobutamine and milrinone, calcium sensitisers increase myocardial contractility without increasing cytosolic calcium release, reducing myocardial energy demand and the incidence of serious arrhythmias. Clinical trials have focused on demonstrating improved survival with levosimendan when compared to placebo and dobutamine. Levosimendan is the first intravenous calcium sensitiser to be approved in Europe for the treatment of acute decompensated heart failure.

Pharmacology

Chemical structure

Levosimendan is a pyridazinone-dinitrile derivative with the chemical name ((R) − (4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-phenyl)hydrazono)propanedinitrile. Levosimendan is the levo-isomer of the racemic compound simendan. It is moderately lipophilic with a small molecular weight (280.29) and is a weak acid (pKa 6.26).

Pharmacological action

β-adrenergic agonists and phosphodiesterase inhibitors produce positive inotropic effects by increasing intracellular concentrations of free calcium. This energy-dependent process involves increasing the intracellular concentration of cyclic adenosine monophosphate (cAMP). Levosimendan has a dual mechanism of action, acting as a positive inotrope and a vasodilator. The positive inotropic effect of levosimendan is achieved by calcium sensitisation rather than increasing intracellular free calcium concentration, therefore avoiding the energy-dependent process. Levosimendan binds to cardiac troponin C and stabilises the conformational changes of troponin C, facilitating actin-myosin cross-bridge formation. This binding occurs in a calcium concentration-dependent manner.

Type
Chapter
Information
Recent Advances in Anaesthesia and Intensive Care , pp. 131 - 142
Publisher: Cambridge University Press
Print publication year: 2007

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References

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  • Levosimendan
    • By Scott Mercer, Pharmacy St Thomas' Hospital Lambeth Palace Road London SEI 7EH UK, Andrew Rhodes, St George's Hospital Blackshaw Road London SW17 0QT UK
  • Edited by Jeremy Cashman, Michael Grounds
  • Book: Recent Advances in Anaesthesia and Intensive Care
  • Online publication: 15 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544521.009
Available formats
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Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Levosimendan
    • By Scott Mercer, Pharmacy St Thomas' Hospital Lambeth Palace Road London SEI 7EH UK, Andrew Rhodes, St George's Hospital Blackshaw Road London SW17 0QT UK
  • Edited by Jeremy Cashman, Michael Grounds
  • Book: Recent Advances in Anaesthesia and Intensive Care
  • Online publication: 15 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544521.009
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Levosimendan
    • By Scott Mercer, Pharmacy St Thomas' Hospital Lambeth Palace Road London SEI 7EH UK, Andrew Rhodes, St George's Hospital Blackshaw Road London SW17 0QT UK
  • Edited by Jeremy Cashman, Michael Grounds
  • Book: Recent Advances in Anaesthesia and Intensive Care
  • Online publication: 15 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544521.009
Available formats
×