Milrinone

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Milrinone
Clinical data
Drug class

Positive inotrope

Contraindications

Milrinone hypersensitivity

Routes of administration

Intravenous

Dosage
Pharmacodynamics
Mechanism of action

Phosphodiesterase inhibitor

Adverse effects

Hypotension, arrhythmia, headache, syncope, bronchospasm

Pharmacokinetics
Onset of action

2-10 minutes

Duration of action

variable, 1.5-5 hours

Metabolism

Liver glucuronidation

Elimination half-life

2.4 hours (heart failure patients)

Clearance

0.14 L/kg/hr (heart failure patients)

Protein binding

70%

Volume of distribution

0.45 L/kg

Physical and chemical data
Formula

C12H9N3O

Molar mass

211.22 g/mol

Article quality
Editor rating
Comprehensive
User likes
0

Milrinone is a phosphodiesterase III inhibitor, which increases cardiac contractility and induces both peripheral and pulmonary vasodilation. Its primary indication is for short-term treatment of acute decompensated heart failure with reduced ejection fraction. Milrinone is more likely to cause hypotension and less likely to cause arrhythmias when compared to other inotropes, such as dobutamine and dopamine.[1]

Uses

  • Short-term treatment of acute decompensated heart failure with reduced ejection fraction[2]
  • Treat of cerebral vasospasm after aneurysmal subarachnoid hemorrhage[3]
  • Treatment of persistent pulmonary hypertension of the newborn in patients with poor response to nitric oxide

Contraindications

Absolute contraindications

  • Milrinone hypersensitivity
  • Corn hypersensitivity, as some formulations contain dextrose[2]

Precautions

  • Idiopathic hypertrophic subaortic stenosis
  • Acute myocardial infarction
  • Atrial fibrillation or flutter
  • Renal impairment or failure
  • Hypovolemia
  • Hypokalemia
  • Pregnancy or breast-feeding

Pharmacology

Pharmacodynamics

Mechanism of action

Milrinone is an inotrope and vasodilator without significant chronotropic activity. Milrinone selectively inhibits phosphodiesterase III, preventing the breakdown of cAMP in cardiac myocytes and smooth muscle cells. This preserved cAMP increases protein kinase A activity, leading to phosphorylation of calcium ion channels in the sarcoplasmic reticulum and increasing calcium availability in myocyte sarcomere. The aforementioned increased calcium availability results in enhanced cardiac inotropy and chronotropy. In vascular smooth muscle cells, phosphodiesterase III inhibition promotes vasodilation and reduces systemic vascular resistance. Similarly, it decreases pulmonary vascular resistance. [4]

Adverse effects

  • Ventricular or Atrial arrhythmia[5]
  • Sudden cardiac death
  • Headache
  • Syncope
  • Hypotension
  • Injection site reaction
  • Tremor
  • Bronchospasm and anaphylactic shock

Pharmacokinetics

  • Onset of action typically within 2 minutes, though peak effect is closer to 10 minutes in patients with heart failure[2]
  • Duration of action: highly variable, but generally 1.5-5 hours
  • Metabolized in the liver via glucuronidation to an O-glucuride metabolite
  • Milrinone and metabolite are cleared in the urine
  • Elimination half-life: 2.4 hours

Chemistry and formulation

Milrinone is a bipyridine.

History

References

  1. Jentzer, Jacob C.; Coons, James C.; Link, Christopher B.; Schmidhofer, Mark (2014-11-28). "Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit". Journal of Cardiovascular Pharmacology and Therapeutics. 20 (3): 249–260. doi:10.1177/1074248414559838. ISSN 1074-2484.
  2. 2.0 2.1 2.2 Milrinone injection package insert. Deerfield, IL: Baxter Healthcare Corporation. 2018.
  3. Fraticelli, Amanda Tarabini; Cholley, Bernard P.; Losser, Marie-Reine; Saint Maurice, Jean-Pierre; Payen, Didier (2008-03). "Milrinone for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage". Stroke. 39 (3): 893–898. doi:10.1161/strokeaha.107.492447. ISSN 0039-2499. Check date values in: |date= (help)
  4. Dobashi, Shintaro; Watanabe, Ippei; Nakanishi, Rine; Hisatake, Shinji; Kiuchi, Shunsuke; Kabuki, Takayuki; Oka, Takashi; Fujii, Takahiro; Ikeda, Takanori (2019-12-21). "Comparing the effects of milrinone and olprinone in patients with congestive heart failure". Heart and Vessels. 35 (6): 776–785. doi:10.1007/s00380-019-01543-6. ISSN 0910-8327.
  5. Chong, Luke Yong Zheng; Satya, Kumar; Kim, Bernard; Berkowitz, Robert (2018-01). "Milrinone Dosing and a Culture of Caution in Clinical Practice". Cardiology in Review. 26 (1): 35–42. doi:10.1097/crd.0000000000000165. ISSN 1061-5377. Check date values in: |date= (help)