Milrila K
Milrila K Uses, Dosage, Side Effects, Food Interaction and all others data.
Heart failure is a multifactorial condition that affects roughly 1-2% of the adult population. Often the result of long-term myocardial ischemia, cardiomyopathy, or other cardiac insults, heart failure results from an inability of the heart to perfuse peripheral tissues with sufficient oxygen and metabolites, resulting in complex systemic pathologies. Heart failure is underpinned by numerous physiological changes, including alteration in β-adrenergic signalling and cyclic adenosine monophosphate (cAMP) production, which affects the heart's contractile function and cardiac output. Milrila K is a second-generation bipyridine phosphodiesterase (PDE) inhibitor created through chemical modification of amrinone. As a PDE-III inhibitor, milrinone results in increased cAMP levels and improves cardiac function and peripheral vasodilation in acute decongested heart failure.
Milrila K was originally synthesized at the Sterling Winthrop Research Institute in the 1980s. It was approved by the FDA on December 31, 1987, and was marketed under the trademark PRIMACOR® by Sanofi-Aventis US before being discontinued.
Milrila K is a bipyridine derivative with positive inotropic and lusitropic effects that also results in peripheral vasodilation with minimal chronotropic effects over a therapeutic range of 100 to 300 ng/mL. As such, milrinone is used in decompensated congestive heart failure. Studies have demonstrated that milrinone exhibits sigmoidal effects, such that increasing milrinone plasma concentrations beyond a certain level results in no further hemodynamic changes. Despite milrinone's benefits, both intravenous and oral use has been associated with increased frequency of ventricular arrhythmias, and long-term oral use has been associated with an increased risk of sudden death; in general, there are no data to support the safety or efficacy of milrinone use beyond 48 hours and patients should be monitored closely for cardiac dysfunction. Also, as milrinone is primarily excreted renally, dose adjustments may be required in patients with impaired renal function.
| Trade Name | Milrila K |
| Availability | Prescription only |
| Generic | Milrinone |
| Milrinone Other Names | Milrinona, Milrinone, Milrinonum |
| Related Drugs | amlodipine, lisinopril, metoprolol, furosemide, carvedilol, spironolactone |
| Type | |
| Formula | C12H9N3O |
| Weight | Average: 211.2194 Monoisotopic: 211.074561925 |
| Protein binding | Milrinone is approximately 70% bound to human plasma proteins. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Japan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Milrila K is a PDE-III inhibitor with inotropic, lusitropic, and vasodilatory properties used for the short-term treatment of acute decompensated heart failure.
Milrila K is indicated for the short-term (48 hours or less) treatment of patients with acute decompensated heart failure. Milrila K administration should occur together with close monitoring using appropriate electrocardiographic equipment and should occur in a facility equipped for the immediate treatment of potential cardiac events, including ventricular arrhythmias.
Milrila K is also used to associated treatment for these conditions: Acute Decompensated Heart Failure (ADHF), Congestive Heart Failure (CHF)
How Milrila K works
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. 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. 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.
Milrila K is a partial competitive inhibitor of phosphodiesterase III (PDE-III), with a measured IC50 value of between 0.66 and 1.3 μM. 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. 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.
Toxicity
Toxicity information regarding milrinone is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hypotension and adverse cardiac events such as ventricular arrhythmias. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Milrila K Disease Interaction
Major: arrhythmias, heart valve disease, myocardial infarctionModerate: liver disease, hypotension, thrombocytopenia
Volume of Distribution
Milrila K administered intravenously to congestive heart failure patients had a volume of distribution of 0.38 L/kg (injections between 12.5-125 μg/kg) and 0.45 L/kg (infusions between 0.2-0.7 μg/kg/min.
Elimination Route
When administered as an IV bolus dose of 10-100 μg/kg, milrinone induces hemodynamic effects within 60 seconds reaching a peak effect by 2-5 minutes. The plasma AUC is significantly dose-dependent.
Half Life
Milrila K administered intravenously to congestive heart failure patients had a mean terminal elimination half-life of 2.3 hours (injections between 12.5-125 μg/kg) and 2.4 hours (infusions between 0.2-0.7 μg/kg/min.
Clearance
Milrila K administered intravenously to congestive heart failure patients had a clearance of 0.13 L/kg/hr (injections between 12.5-125 μg/kg) and 0.14 L/kg/hr (infusions between 0.2-0.7 μg/kg/min.
Elimination Route
Milrila K is primarily excreted in the urine, with 60% of a dose recovered after two hours and 90% within eight hours. Approximately 83% of milrinone recovered in urine is unchanged while 12% is present as the main O-glucuronide metabolite.
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