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Inamrinone (previously called amrinone) and milrinone arebipyridine compounds that inhibit phosphodiesterase isozyme 3 (PDE-3). They are active orally as well as parenterally but are available only in parenteral forms. They have elimination half-lives of 3–6 hours, with 10–40% being excreted in the urine.
The bipyridines increase myocardial contractility by increasing inward calcium flux in the heart during the action potential; they may also alter the intracellular movements of calcium by influencing the sarcoplasmic reticulum. They also have an important vasodilat-ing effect. Inhibition of phosphodiesterase results in an increase in cAMP and the increase in contractility and vasodilation.
The toxicity of inamrinone includes nausea and vomiting; arrhythmias, thrombocytopenia, and liver enzyme changes have also been reported in a significant number of patients. This drug has been withdrawn in some countries. Milrinone appears less likely to cause bone marrow and liver toxicity than inamrinone, but it does cause arrhythmias. Inamrinone and milrinone are now used only intravenously and only for acute heart failure or severe exacerbation of chronic heart failure.
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