Difference between revisions of "Milrinone"
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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.<ref>{{Cite journal|last=Jentzer|first=Jacob C.|last2=Coons|first2=James C.|last3=Link|first3=Christopher B.|last4=Schmidhofer|first4=Mark|date=2014-11-28|title=Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit|url=http://dx.doi.org/10.1177/1074248414559838|journal=Journal of Cardiovascular Pharmacology and Therapeutics|volume=20|issue=3|pages=249–260|doi=10.1177/1074248414559838|issn=1074-2484}}</ref> | '''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]].<ref>{{Cite journal|last=Jentzer|first=Jacob C.|last2=Coons|first2=James C.|last3=Link|first3=Christopher B.|last4=Schmidhofer|first4=Mark|date=2014-11-28|title=Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit|url=http://dx.doi.org/10.1177/1074248414559838|journal=Journal of Cardiovascular Pharmacology and Therapeutics|volume=20|issue=3|pages=249–260|doi=10.1177/1074248414559838|issn=1074-2484}}</ref> | ||
== Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. --> == | ==Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. -->== | ||
* Short-term treatment of acute decompensated heart failure with reduced ejection fraction<ref name=":0">{{Cite book|title=Milrinone injection package insert|publisher=Baxter Healthcare Corporation|year=2018|location=Deerfield, IL}}</ref> | *Short-term treatment of acute decompensated heart failure with reduced ejection fraction<ref name=":0">{{Cite book|title=Milrinone injection package insert|publisher=Baxter Healthcare Corporation|year=2018|location=Deerfield, IL}}</ref> | ||
* Treat of cerebral vasospasm after aneurysmal subarachnoid hemorrhage<ref>{{Cite journal|last=Fraticelli|first=Amanda Tarabini|last2=Cholley|first2=Bernard P.|last3=Losser|first3=Marie-Reine|last4=Saint Maurice|first4=Jean-Pierre|last5=Payen|first5=Didier|date=2008-03|title=Milrinone for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage|url=http://dx.doi.org/10.1161/strokeaha.107.492447|journal=Stroke|volume=39|issue=3|pages=893–898|doi=10.1161/strokeaha.107.492447|issn=0039-2499}}</ref> | *Treat of cerebral vasospasm after aneurysmal subarachnoid hemorrhage<ref>{{Cite journal|last=Fraticelli|first=Amanda Tarabini|last2=Cholley|first2=Bernard P.|last3=Losser|first3=Marie-Reine|last4=Saint Maurice|first4=Jean-Pierre|last5=Payen|first5=Didier|date=2008-03|title=Milrinone for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage|url=http://dx.doi.org/10.1161/strokeaha.107.492447|journal=Stroke|volume=39|issue=3|pages=893–898|doi=10.1161/strokeaha.107.492447|issn=0039-2499}}</ref> | ||
* Treatment of persistent pulmonary hypertension of the newborn in patients with poor response to nitric oxide | *Treatment of persistent pulmonary hypertension of the newborn in patients with poor response to nitric oxide | ||
== Contraindications<!-- List contraindications and precautions for use of the drug. --> == | ==Contraindications<!-- List contraindications and precautions for use of the drug. -->== | ||
=== Absolute contraindications<!-- List absolute contraindications for use of the drug. If none, this section may be removed. --> === | ===Absolute contraindications<!-- List absolute contraindications for use of the drug. If none, this section may be removed. -->=== | ||
* Milrinone hypersensitivity | *Milrinone hypersensitivity | ||
* Corn hypersensitivity, as some formulations contain dextrose<ref name=":0" /> | *Corn hypersensitivity, as some formulations contain dextrose<ref name=":0" /> | ||
=== Precautions<!-- List precautions for use of the drug. If none, this section may be removed. --> === | ===Precautions<!-- List precautions for use of the drug. If none, this section may be removed. -->=== | ||
* Idiopathic hypertrophic subaortic stenosis | *Idiopathic hypertrophic subaortic stenosis | ||
* Acute myocardial infarction | *Acute myocardial infarction | ||
* Atrial fibrillation or flutter | *Atrial fibrillation or flutter | ||
* Renal impairment or failure | *Renal impairment or failure | ||
* Hypovolemia | * Hypovolemia | ||
* Hypokalemia | * Hypokalemia | ||
* Pregnancy or breast-feeding | *Pregnancy or breast-feeding | ||
== Pharmacology == | ==Pharmacology== | ||
=== Pharmacodynamics<!-- Describe the effects of the drug on the body. If appropriate, add subsections by organ system --> === | ===Pharmacodynamics<!-- Describe the effects of the drug on the body. If appropriate, add subsections by organ system -->=== | ||
==== Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. --> ==== | ====Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. -->==== | ||
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. <ref>{{Cite journal|last=Dobashi|first=Shintaro|last2=Watanabe|first2=Ippei|last3=Nakanishi|first3=Rine|last4=Hisatake|first4=Shinji|last5=Kiuchi|first5=Shunsuke|last6=Kabuki|first6=Takayuki|last7=Oka|first7=Takashi|last8=Fujii|first8=Takahiro|last9=Ikeda|first9=Takanori|date=2019-12-21|title=Comparing the effects of milrinone and olprinone in patients with congestive heart failure|url=http://dx.doi.org/10.1007/s00380-019-01543-6|journal=Heart and Vessels|volume=35|issue=6|pages=776–785|doi=10.1007/s00380-019-01543-6|issn=0910-8327}}</ref> | 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. <ref>{{Cite journal|last=Dobashi|first=Shintaro|last2=Watanabe|first2=Ippei|last3=Nakanishi|first3=Rine|last4=Hisatake|first4=Shinji|last5=Kiuchi|first5=Shunsuke|last6=Kabuki|first6=Takayuki|last7=Oka|first7=Takashi|last8=Fujii|first8=Takahiro|last9=Ikeda|first9=Takanori|date=2019-12-21|title=Comparing the effects of milrinone and olprinone in patients with congestive heart failure|url=http://dx.doi.org/10.1007/s00380-019-01543-6|journal=Heart and Vessels|volume=35|issue=6|pages=776–785|doi=10.1007/s00380-019-01543-6|issn=0910-8327}}</ref> | ||
==== Adverse effects<!-- Describe any potential adverse effects of the drug. --> ==== | ====Adverse effects<!-- Describe any potential adverse effects of the drug. -->==== | ||
* Ventricular or Atrial arrhythmia<ref>{{Cite journal|last=Chong|first=Luke Yong Zheng|last2=Satya|first2=Kumar|last3=Kim|first3=Bernard|last4=Berkowitz|first4=Robert|date=2018-01|title=Milrinone Dosing and a Culture of Caution in Clinical Practice|url=http://dx.doi.org/10.1097/crd.0000000000000165|journal=Cardiology in Review|volume=26|issue=1|pages=35–42|doi=10.1097/crd.0000000000000165|issn=1061-5377}}</ref> | *Ventricular or Atrial arrhythmia<ref>{{Cite journal|last=Chong|first=Luke Yong Zheng|last2=Satya|first2=Kumar|last3=Kim|first3=Bernard|last4=Berkowitz|first4=Robert|date=2018-01|title=Milrinone Dosing and a Culture of Caution in Clinical Practice|url=http://dx.doi.org/10.1097/crd.0000000000000165|journal=Cardiology in Review|volume=26|issue=1|pages=35–42|doi=10.1097/crd.0000000000000165|issn=1061-5377}}</ref> | ||
* Sudden cardiac death | *Sudden cardiac death | ||
* Headache | *Headache | ||
* Syncope | *Syncope | ||
* Hypotension | * Hypotension | ||
* Injection site reaction | *Injection site reaction | ||
* Tremor | *Tremor | ||
* Bronchospasm and anaphylactic shock | *Bronchospasm and anaphylactic shock | ||
=== Pharmacokinetics<!-- Describe the pharmacokinetics of the drug. --> === | ===Pharmacokinetics<!-- Describe the pharmacokinetics of the drug. -->=== | ||
* Onset of action typically within 2 minutes, though peak effect is closer to 10 minutes in patients with heart failure<ref name=":0" /> | *Onset of action typically within 2 minutes, though peak effect is closer to 10 minutes in patients with heart failure<ref name=":0" /> | ||
* Duration of action: highly variable, but generally 1.5-5 hours | *Duration of action: highly variable, but generally 1.5-5 hours | ||
* Metabolized in the liver via glucuronidation to an O- | *Metabolized in the liver via glucuronidation to an O-glucuronide metabolite | ||
* Milrinone and metabolite are cleared in the urine | *Milrinone and metabolite are cleared in the urine | ||
* Elimination half-life: 2.4 hours | *Elimination half-life: 2.4 hours | ||
== Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. --> == | ==Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. -->== | ||
Milrinone is a bipyridine. | Milrinone is a bipyridine. | ||
== History<!-- Describe the historical development of the drug. --> == | ==History<!-- Describe the historical development of the drug. -->== | ||
== References == | ==References== | ||
[[Category:Drug reference]] | [[Category:Drug reference]] | ||
<references /> | |||
[[Category:Positive inotropes]] | |||
Latest revision as of 17:30, 10 January 2024
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 | |
| 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-glucuronide metabolite
- Milrinone and metabolite are cleared in the urine
- Elimination half-life: 2.4 hours
Chemistry and formulation
Milrinone is a bipyridine.
History
References
- ↑ 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.
- ↑ 2.0 2.1 2.2 Milrinone injection package insert. Deerfield, IL: Baxter Healthcare Corporation. 2018.
- ↑ 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) - ↑ 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.
- ↑ 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)
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