milrinone

Action and Spectrum

Actions and Spectrum: 

milrinone is a phosphodiesterase type 3 (PDE3) inhibitor, which means it works by inhibiting the enzyme PDE3 and thereby increasing the levels of cyclic adenosine monophosphate (cAMP) in the body. This leads to several actions and effects on the body: 

• Vasodilation: milrinone increases blood flow to the heart and other organs by relaxing smooth muscle in the blood vessels, thus reducing afterload and increasing cardiac output. 
• Positive inotropy: milrinone increases the contractility of the heart, which improves the heart’s ability to pump blood. 
• Chronotropy: milrinone increases the heart rate, which helps to improve cardiac output. 
• Anti-ischemic: milrinone improves blood flow to the heart, which can reduce the risk of ischemia (lack of oxygen to the heart) and angina (chest pain). 
• Diuretic: milrinone can increase the production of urine and reduce fluid accumulation in the body, which can be beneficial in patients with heart failure or pulmonary edema (fluid buildup in the lungs). 

Overall, the spectrum of milrinone includes: 

• Vasodilation 
• Positive inotropy 
• Chronotropy 
• Anti-ischemic 
• Diuretic 

It is mostly used to treat heart failure and cardiogenic shock. 

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10%  

Headache (3%)  

Angina/chest pain (1%)  

Hypotension (3%)  

Supraventricular arrhythmia (4%)  

>10%  

Ventricular arrhythmias  

<1%  

Atrial fibrillation  

Anaphylaxis  

Bronchospasm  

Injection-site reaction  

Hypokalemia  

Rash  

Tremor  

Thrombocytopenia   

Black Box Warning

Black Box Warning 

The black box warning for milrinone states that the drug may cause serious or life-threatening heart problems, such as ventricular arrhythmias (irregular heartbeats) or heart failure. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to milrinone 
• Cardiogenic shock 
• Severe ventricular dysfunction 

Caution: 

• Pulmonary hypertension 
• Cardiac arrhythmias 
• Renal or hepatic impairment 
• Low blood pressure (hypotension) 
• Use with other inotropes or vasodilators 
• Use in patients with electrolyte imbalances (such as low potassium levels) 
• Use in elderly patients or those with compromised cardiac function as they may be more susceptible to side effects. 

Pregnancy / Lactation

Pregnancy warnings:     

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk is unknown  

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

milrinone is primarily used to treat heart failure and reduce the workload on the heart in patients with acute decompensated heart failure. It is also used to treat low cardiac output states in patients undergoing surgery or in critically ill patients. 

Pharmacodynamics:  

The drug milrinone is a member of the phosphodiesterase-3 inhibitors pharmacological class. 

It functions by raising the concentrations of cyclic adenosine monophosphate (cAMP) in the heart and blood arteries, which increases the force with which the heart muscle contracts. 

This aids in enhancing blood flow and lowering pulmonary pressure.  

Pharmacokinetics:  

Absorption   

It is rapidly absorbed after intravenous administration, with an onset of action within 5-15 minutes. The duration of action is around 3-5 hours, and the peak plasma time is 2 minutes. The therapeutic range for milrinone is 100-300 ng/mL for hemodynamic effect  

Distribution   

The drug is about 70% protein bound and has a VD of 0.38 L/kg for the injection form and 0.45 L/kg for the infusion form  

Metabolism  

milrinone is metabolized in the liver, mainly via glucuronidation, with about 12% of the drug being metabolized. The main metabolite is milrinone O-glucuronide, but its activity is unknown  

Elimination and excretion  

The elimination half-life of milrinone is 2.5 hours and the clearance is 2.3 mL/kg/min. The drug is mainly excreted in the urine, with 95% of the dose excreted, of which 83% is unchanged drug. A small portion of the drug is excreted in the feces 

Adminstartion

Administration:  

milrinone is a medication that is used to treat heart failure and is administered intravenously (IV) by a healthcare professional in a hospital or clinic setting. The usual dosage for adults is a bolus of 50 mcg/kg followed by a continuous infusion of 0.375-0.75 mcg/kg/min. The dosage may be adjusted based on the patient’s response and side effects. Milrinone should be administered with caution in patients with low blood pressure, arrhythmias, or kidney or liver impairment. Close monitoring of vital signs and electrolyte levels is necessary during and after administration of the medication.

Patient Information Leaflet

Patient information leaflet 

Generic Name: milrinone 

Why do we use milrinone? 

milrinone is used to treat heart failure, a condition in which the heart is unable to pump enough blood to meet the body’s needs. It works by relaxing and dilating the blood vessels, which allows for improved blood flow and reduces the workload on the heart. It also increases the heart’s ability to contract, which improves its pumping ability. milrinone is typically used in patients who have acute heart failure, or in patients who are not responding well to other treatments such as diuretics or ACE inhibitors. It is also used in patients who are undergoing certain types of heart surgery to improve cardiac function. By improving blood flow and reducing the workload on the heart, milrinone can help alleviate symptoms of heart failure such as shortness of breath, fatigue, and swelling in the legs and feet.