Milrinone 10mg/50ml solution for infusion pre-filled syringes

Heart failure is a condition characterized by the heart's inability to provide adequate perfusion to the peripheral tissues, resulting in systemic symptoms including pulmonary, gastrointestinal, renal, and cerebral dysfunction.[A228323] Although the biochemical and physiological processes underlying heart failure complex and variable, one such physiological response regulated by the sympathetic nervous system involves the eventual downregulation of cardiac β-receptors, decreased catecholamine sensitivity, and a corresponding decrease in adenylyl-cyclase-mediated signalling pathways.[A228323] Increased intracellular cAMP, mainly acting through protein kinase A, increases sarcolemmal calcium release through L-type calcium channels as well as calcium re-uptake mediated by phospholamban and troponin I; these actions correspond to positive inotropic and lusitropic effects, respectively.[A228323][A228333]

Milrinone is a partial competitive inhibitor of phosphodiesterase III (PDE-III), with a measured IC₅₀ value of between 0.66 and 1.3 μM.[A228338][A11759] As a PDE-III inhibitor, milrinone results in an increase in intracellular cAMP, responsible for its pharmacological effects, including positive inotropy, positive lusitropy, and vasodilation.[A228323][A228333][A228348] As milrinone affects cAMP levels through PDE-III and not through β-adrenergic receptors, it is effective in patients who have downregulated or otherwise desensitized β-adrenergic receptors and can be administered together with β-agonists/antagonists.[A228353][A228358]