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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 3/2004

01-03-2004 | Review Article

Pharmacokinetics and Pharmacodynamics of Intravenous Inotropic Agents

Authors: Dr Lasse A. Lehtonen, Saila Antila, Pertti J. Pentikäinen

Published in: Clinical Pharmacokinetics | Issue 3/2004

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Abstract

Positive inotropic drugs have various mechanisms of action. Long-term use of cyclic adenosine monophosphate (cAMP)-dependent drugs has adverse effects on the prognosis of heart failure patients, whereas digoxin has neutral effect on mortality. There are, however, little data on the effects of intravenous inotropic drugs on the outcome of patients.
Intravenous inotropic agents are used to treat cardiac emergencies and refractory heart failure. β-Adrenergic agonists are rapid acting and easy to titrate, with short elimination half-life. However, they increase myocardial oxygen consumption and are thus hazardous during myocardial ischaemia. Furthermore they may promote myocyte apoptosis. Phosphodiesterase (PDE) III inhibiting drugs (amrinone, milrinone and enoximone) increase contractility by reducing the degradation of cAMP. In addition, they reduce both preload and afterload via vasodilation. Short-term use of intravenous milrinone is not associated with increased mortality, and some symptomatic benefit may be obtained when it is used in refractory heart failure. Furthermore, PDE III inhibitors facilitate weaning from the cardiopulmonary bypass machine after cardiac surgery.
Levosimendan belongs to a new group of positive inotropic drugs, the calcium sensitisers. It has complex pharmacokinetics and long-lasting haemodynamic effects as a result of its active metabolites. In comparative trials, it has been better tolerated than the most widely used β-agonist inotropic drug, dobutamine.
The pharmacokinetics of the intravenous inotropic drugs might sometimes greatly modify and prolong the response to the therapy, for example because of long-acting active metabolites. These drugs display considerable differences in their pharmacokinetics and pharmacodynamics, and the selection of the most appropriate inotropic drug for each patient should be based on careful consideration of the clinical status of the patient and on the pharmacology of the drug.
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Metadata
Title
Pharmacokinetics and Pharmacodynamics of Intravenous Inotropic Agents
Authors
Dr Lasse A. Lehtonen
Saila Antila
Pertti J. Pentikäinen
Publication date
01-03-2004
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 3/2004
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200443030-00003