Usage
- Amrinone is prescribed for the short-term management of acute decompensated heart failure, particularly in patients who have not responded adequately to other treatments such as digitalis, diuretics, and vasodilators. It is generally used as a temporary measure to improve cardiac function while other therapies are initiated or adjusted.
- Pharmacological classification: Inotropic agent, vasodilator.
- Mechanism of Action: Amrinone increases myocardial contractility (positive inotropic effect) and reduces systemic and pulmonary vascular resistance (vasodilator effect). It achieves this primarily by inhibiting phosphodiesterase 3 (PDE3) enzyme, leading to increased intracellular cyclic adenosine monophosphate (cAMP). Elevated cAMP levels promote calcium influx into myocardial cells, enhancing contractile force. Additionally, increased cAMP promotes vasodilation by relaxing vascular smooth muscle.
Alternate Names
- Inamrinone (International Nonproprietary Name - INN)
- Brand name: Inocor
How It Works
- Pharmacodynamics: Amrinone exerts positive inotropic and vasodilator effects. The positive inotropic action increases cardiac output and stroke volume, while the vasodilator effect reduces preload and afterload, further improving cardiac performance.
- Pharmacokinetics:
- Absorption: Administered intravenously, therefore 100% bioavailable. Rapid onset of action (within 5 minutes), peak effect in 10 minutes.
- Distribution: Minimally protein-bound (26-40%), volume of distribution of approximately 1.2 L/kg.
- Metabolism: Metabolized in the liver primarily via conjugation to N-glycolate, N-acetate, O-glucuronide, and N-glucuronide (inactive metabolites).
- Elimination: Primarily renal excretion (approximately 63% unchanged in urine over 96 hours). About 18% of the administered dose is excreted in feces within 72 hours. Elimination half-life is around 2 hours, with effects lasting up to 8 hours.
- Mode of Action: Inhibits phosphodiesterase 3 (PDE3) enzyme, which leads to increased intracellular cAMP, resulting in increased myocardial contractility and vasodilation.
- Receptor Binding/Enzyme Inhibition: Inhibits PDE3 enzyme. No significant receptor binding activity.
Dosage
Standard Dosage
Adults:
- Loading dose: 0.75 mg/kg IV bolus over 2-3 minutes.
- Maintenance infusion: 5-10 mcg/kg/min IV.
- Maximum daily dose (including loading dose): 10 mg/kg/day. In limited cases and for short durations, doses up to 18 mg/kg/day have been administered.
Children (Not FDA approved, use with caution):
- <28 days old:
- Loading dose: 0.75 mg/kg IV over 3-5 minutes.
- Maintenance infusion: 3-5 mcg/kg/min IV.
- Loading dose may be repeated after 30 minutes if needed.
- Maximum daily dose: 10 mg/kg/day.
-
28 days old:
- Loading dose: 0.75 mg/kg IV over 3-5 minutes.
- Maintenance infusion: 5-15 mcg/kg/min IV.
- Maximum daily dose: 10 mg/kg/day.
Special Cases:
- Elderly Patients: Start with lower doses and titrate carefully based on renal function and clinical response. Monitor for hypotension.
- Patients with Renal Impairment: Dose adjustments are needed based on creatinine clearance (CrCl):
- Adults: CrCl <10 mL/min: Administer 50-75% of the dose.
- Children: CrCl 10-29 mL/min: 50% of the dose. CrCl <10 mL/min: 25% of the dose.
- Patients with Hepatic Dysfunction: No specific dosage adjustments provided in current guidelines; monitor closely due to the potential for hepatotoxicity.
Clinical Use Cases
Amrinone is generally used in intensive care or similar settings for acute decompensated heart failure. Dosages for specific situations are as described above and titrated based on patient response and hemodynamic monitoring.
Dosage Adjustments
Dose adjustments based on renal function are outlined above. Monitor patients closely for adverse effects and adjust infusion rate accordingly. Therapeutic range 0.5 - 7 mcg/mL. If there is no response or there is a significant drop in blood pressure, reduce or temporarily suspend infusion.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Fever
- Headache
Rare but Serious Side Effects:
- Thrombocytopenia (low platelet count)
- Cardiac arrhythmias (irregular heartbeat)
- Hepatotoxicity (liver damage)
- Hypotension (low blood pressure)
- Myositis (muscle inflammation)
Contraindications
- Hypersensitivity to amrinone or bisulfites.
Drug Interactions
- Disopyramide: Can cause severe hypotension. Avoid concurrent use.
- Furosemide and dextrose solutions: Physicochemical incompatibility. Do not mix in same IV line.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (animal studies show adverse effects, human studies lacking). Use only if potential benefit outweighs risk.
- Breastfeeding: Not known if excreted in breast milk. Exercise caution.
Drug Profile Summary
- Mechanism of Action: PDE3 inhibitor, leading to increased cAMP, positive inotropic and vasodilator effects.
- Side Effects: Nausea, vomiting, diarrhea, thrombocytopenia, arrhythmias, hepatotoxicity.
- Contraindications: Hypersensitivity to amrinone or bisulfites.
- Drug Interactions: Disopyramide (severe hypotension). Avoid mixing with dextrose solutions or furosemide in IV lines.
- Pregnancy & Breastfeeding: Category C, use with caution.
- Dosage: Adult loading dose 0.75 mg/kg IV bolus, maintenance 5-10 mcg/kg/min. Pediatric doses available, use with caution. Max daily dose 10 mg/kg. Renal adjustments needed.
- Monitoring Parameters: Heart rate, blood pressure, ECG, platelet count, liver function tests, renal function.
Popular Combinations (Amrinone is often used in combination with other heart failure medications, such as:)
- Digitalis glycosides
- Diuretics (e.g., furosemide)
- Vasodilators (e.g., nitrates)
Precautions
- Monitor blood pressure, heart rate and rhythm, platelet count, and liver function during therapy.
- Use cautiously in patients with recent myocardial infarction, electrolyte abnormalities, hypotension, and severe aortic or pulmonic valvular disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amrinone?
A: Adult loading dose: 0.75 mg/kg IV bolus over 2-3 min. Maintenance: 5-10 mcg/kg/min. Pediatric and renal adjustments provided above.
Q2: What is the mechanism of action of Amrinone?
A: Amrinone inhibits phosphodiesterase 3, increasing intracellular cAMP and leading to positive inotropic and vasodilator effects.
Q3: What are the major side effects of Amrinone?
A: Common side effects include nausea, vomiting, and diarrhea. Serious side effects include thrombocytopenia, arrhythmias, and hepatotoxicity.
Q4: What are the contraindications for using Amrinone?
A: Hypersensitivity to amrinone or bisulfites.
Q5: What are the significant drug interactions with Amrinone?
A: Concurrent use of disopyramide can cause severe hypotension. Do not mix with dextrose or furosemide in IV lines.
Q6: Can Amrinone be used during pregnancy and breastfeeding?
A: Pregnancy Category C, use with caution if benefits outweigh risks. Excretion in breast milk unknown, exercise caution.
Q7: What monitoring parameters are essential when administering Amrinone?
A: Monitor heart rate, blood pressure, ECG, platelet count, liver function tests, and renal function.
Q8: What is the role of Amrinone in the intensive care unit?
A: Short-term management of acute decompensated heart failure, often in patients not responding adequately to other treatments.
Q9: What is the difference between amrinone and milrinone?
A: Both are PDE3 inhibitors but milrinone has a longer half-life and may cause less thrombocytopenia.
Q10: How should Amrinone be administered?
A: Administered intravenously, loading dose over 2-3 minutes followed by continuous infusion. Use normal or half-normal saline for dilution; do not mix with dextrose solutions.
