inamrinone

Action and Spectrum

Actions and Spectrum: 

inamrinone is a medication that belongs to a class of drugs known as phosphodiesterase inhibitors. It is used for the treatment of congestive heart failure. Here’s some information about its action and spectrum: 

Action: inamrinone inhibits the enzyme phosphodiesterase III, which breaks down cyclic adenosine monophosphate (cAMP) in cardiac and smooth muscle cells. By inhibiting this enzyme, inamrinone increases the levels of cAMP, leading to several effects: 

• Positive Inotropic Effect: inamrinone enhances heart muscle contractility. It increases the calcium for contraction, leading to more muscular and forceful contractions. 
• Vasodilation: inamrinone causes relaxation and dilation of blood vessels, primarily the arteries, leading to decreased resistance against which the heart must pump. This diminishes the workload on the heart and helps improve blood flow. 

Spectrum: inamrinone is mainly used to treat acute decompensated heart failure (ADHF), a condition the heart generally cannot pump enough blood to meet the body’s demands. It is typically reserved for short-term use in hospitalized patients who have not responded adequately to other therapies. inamrinone is usually administered intravenously. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Nausea (1.7%) 

Thrombocytopenia (2.4%) 

Hypotension (1.3%) 

Arrhythmia (3%) 

<1% 

Chest pain (0.2%) 

Injections site pain (0.2%) 

Abdominal pain (0.4%) 

Anorexia (0.4%) 

Fever (0.9%) 

Vomiting (0.9%) 

Hepatotoxicity (rare) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

inamrinone has several contraindications, meaning situations or conditions in which medication use is not recommended. Here are some common contraindications for inamrinone: 

• Hypersensitivity: inamrinone should not be used in individuals with known hypersensitivity or allergic reactions to the medication. 
• Severe aortic or pulmonic valvular disease: inamrinone is contraindicated in patients with severe aortic or pulmonic valvular disease because it can increase the obstruction to blood flow through these valves. 
• Obstructive hypertrophic cardiomyopathy: inamrinone is contraindicated in patients with obstructive hypertrophic cardiomyopathy (a condition where the heart muscle becomes abnormally thick), as it may worsen the obstruction to blood flow from the heart. 
• Known or suspected ventricular arrhythmias: inamrinone should not be used in patients with known/suspected ventricular arrhythmias, as it may increase the risk of arrhythmias. 
• Recent myocardial infarction: inamrinone is contraindicated in patients with recent myocardial infarction (heart attack) because it may increase myocardial oxygen demand and potentially worsen ischemia. 
• Concurrent use of intravenous beta-blockers: inamrinone should not be administered concurrently with intravenous beta-blockers because of the potential for additive adverse inotropic effects. 

Caution 

While there are no specific black box warnings associated with inamrinone, there are certain cautions and precautions needed to maintain when using this medication. These include: 

• Renal Impairment: inamrinone is primarily eliminated by the kidneys. Therefore, caution should be exercised when administering inamrinone to patients with impaired renal function. Dose adjustments or close monitoring may be necessary in such cases. 
• Hepatic Impairment: inamrinone is metabolized in the liver. Patients with hepatic impairment may require dose adjustments or careful monitoring when using inamrinone. 
• Hypotension: inamrinone can cause a decrease in blood pressure. Therefore, caution is advised when administering this drug to patients with hypotension or those at risk of developing low blood pressure. Blood pressure should be closely monitored during therapy. 
• Ventricular Arrhythmias: inamrinone has been associated with an increased risk of ventricular arrhythmias. Caution should be exercised when using inamrinone in patients with a history of arrhythmias or those at an increased risk of arrhythmias. 
• Electrolyte Imbalance: inamrinone may affect electrolyte levels, particularly potassium, and magnesium. Monitoring electrolyte levels and correcting any imbalances as necessary during inamrinone therapy is essential. 
• Efficacy in Chronic Heart Failure: inamrinone is primarily used for short-term therapy of acute decompensated heart failure and is not recommended for the long-term use in chronic heart failure. Its benefits in chronic heart failure are limited, and alternative treatments are preferred. 
• Interactions with Other Medications: inamrinone may interact with other medications, including beta-blockers, calcium channel blockers, and other positive inotropic agents. Reviewing a patient’s medication profile and considering potential drug interactions before initiating inamrinone therapy is essential. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• 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 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: 

inamrinone, or inamrinone lactate, is a phosphodiesterase III inhibitor with favorable inotropic and vasodilatory properties. Its pharmacology involves multiple mechanisms of action. Here are the critical pharmacological aspects of inamrinone: 

• Inhibition of Phosphodiesterase III: inamrinone inhibits the enzyme phosphodiesterase III, primarily found in cardiac and smooth muscle cells. By inhibiting this enzyme, inamrinone prevents the breakdown of cyclic adenosine monophosphate (cAMP), increasing cAMP levels within the cells. 
• Positive Inotropic Effect: Increased cAMP levels in cardiac muscle cells enhance contractility (positive inotropic effect). inamrinone increases intracellular calcium concentrations, facilitating more substantial and forceful heart muscle contractions. This effect helps improve cardiac output and overall heart function. 
• Vasodilation: inamrinone also promotes vasodilation, primarily in arterial smooth muscle. It relaxes the smooth muscle in the arterial walls, leading to the dilation of the blood vessels. This effect reduces peripheral vascular resistance and afterload on the heart, easing the heart’s workload and improving blood flow throughout the body. 
• Increased Coronary Blood Flow: inamrinone has increased coronary blood flow, improving oxygen and nutrient supply to the heart muscle. 
• Short Half-Life: inamrinone has a relatively short half-life of about 2 to 3 hours. This shorter duration of action necessitates continuous intravenous infusion to maintain therapeutic levels in the bloodstream. 

Pharmacodynamics: 

Mechanism of action: The action of inamrinone is primarily related to its ability to inhibit the enzyme phosphodiesterase III (PDE-III). Phosphodiesterase III is an enzyme in cardiac and smooth muscle cells responsible for breaking down cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). 

By inhibiting PDE-III, inamrinone prevents the breakdown of cAMP, leading to an increase in intracellular levels of cAMP. Increased cAMP levels in cardiac muscle cells enhance contractility (positive inotropic effect) and increase intracellular calcium concentrations, leading to more substantial and forceful heart muscle contractions. This effect helps improve cardiac output and overall heart function. 

Pharmacokinetics: 

Absorption 

inamrinone is administered intravenously, resulting in rapid and complete absorption into the systemic circulation. Due to its intravenous administration, no oral bioavailability data are available for inamrinone. 

Distribution 

inamrinone has a moderate volume of distribution, ranging from approximately 0.7 to 2.4 L/kg. It distributes throughout the body, including the myocardium, with concentrations in cardiac tissue higher than in plasma. 

Metabolism 

inamrinone undergoes hepatic metabolism via glucuronidation. The primary metabolite of inamrinone is inamrinone glucuronide. This metabolite is pharmacologically active but less potent than the parent compound. inamrinone is considered a prodrug, as it is rapidly converted to inamrinone glucuronide in the liver. 

Elimination and Excretion 

inamrinone and its metabolite, inamrinone glucuronide, are primarily excreted in the urine. Renal elimination accounts for the majority of the drug’s clearance. The elimination half-life of inamrinone is relatively short, ranging from approximately 2 to 6 hours. 

Adminstartion

Administration: 

Intravenous administration 

inamrinone is administered intravenously, typically in a hospital setting, under the supervision of healthcare professionals. Here are some general guidelines for the administration of inamrinone: 

• Dilution: inamrinone is usually supplied as a concentrated solution and needs to be diluted before administration. Follow the instruction provided by the manufacturer or the prescribing healthcare professional for proper dilution. Typically, it is diluted in a compatible intravenous solution, such as normal saline (0.9% sodium chloride) or 5% dextrose in water. 
• Infusion Rate: The infusion rate of inamrinone can differ depending on the individual patient’s condition and response. It is typically administered as a continuous intravenous infusion. The infusion rate is usually determined by the healthcare professional and is based on factors such as the patient’s weight, cardiac output, and response to therapy. 
• Monitoring: Close monitoring is essential during the administration of inamrinone. This includes monitoring vital signs (such as bp, heart rate, and oxygen saturation), cardiac function, electrolyte levels, and renal function. Electrocardiogram (ECG) monitoring may also be performed to assess for any potential arrhythmias. 
• Duration of Treatment: inamrinone is generally used for short-term treatment of acute decompensated heart failure in a hospital setting. The duration of treatment can differ based on the patient’s response and clinical condition. The healthcare professional will determine the appropriate duration of therapy. 

It’s important to note that inamrinone should be administered by healthcare professionals who are experienced in its use and under appropriate medical supervision. They will consider the individual patient’s needs, response to treatment, and any potential contraindications or cautions before initiating and adjusting the dosage of inamrinone. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: inamrinone 

Why do we use inamrinone? 

inamrinone is primarily used for the short-term treatment of acute decompensated heart failure in a hospital setting. Acute decompensated heart failure (ADHF) is a sudden worsening of symptoms in individuals with pre-existing heart failure. Here are the primary uses of inamrinone: 

• Acute Decompensated Heart Failure: inamrinone improves cardiac function and alleviates symptoms in patients with ADHF. It is generally reserved for cases where other treatments, such as diuretics and vasodilators, have not provided sufficient relief. 

inamrinone works by increasing the contractility (positive inotropic effect) of the heart muscle and promoting vasodilation, which diminishes the workload on the heart and improves blood flow. These effects help improve cardiac output and relieve symptoms such as shortness of breath (SOB), fatigue, and fluid retention. 

It’s important to note that inamrinone is not commonly used as a long-term therapy for chronic heart failure, as its benefits in this setting are limited, and it carries a risk of side effects. Other medications, like angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and diuretics, are typically preferred to manage chronic heart failure.