Why does Amiodarone (antiarrhythmic medication) cause hypotension?

From the Guidelines

Amiodarone causes hypotension primarily through its vasodilatory effects and negative inotropic properties, which can be exacerbated by its solvent and rapid intravenous administration. When administered intravenously, amiodarone can cause acute hypotension due to its solvent (polysorbate 80) which produces peripheral vasodilation, reducing systemic vascular resistance 1. Additionally, amiodarone blocks calcium channels and beta-adrenergic receptors, leading to decreased cardiac contractility and heart rate, which further contributes to blood pressure reduction. The drug also has alpha-adrenergic blocking effects that cause vasodilation of peripheral blood vessels. These combined mechanisms decrease both cardiac output and peripheral vascular resistance, resulting in hypotension.

Some key points to consider when administering amiodarone include:

• The risk of hypotension is highest with rapid intravenous administration, which is why IV amiodarone should be given slowly (typically over 10 minutes for a 150mg loading dose) and patients should be monitored for blood pressure changes 1.
• Oral amiodarone is less likely to cause acute hypotension as the drug is absorbed gradually, allowing for compensatory mechanisms to maintain blood pressure.
• Patients with pre-existing left ventricular dysfunction are particularly susceptible to amiodarone-induced hypotension due to their limited cardiac reserve.
• The dosage guidelines for amiodarone, as outlined in the American Family Physician guidelines, recommend a 150-mg IV bolus over 10 minutes for life-threatening arrhythmia, with potential adverse effects including hypotension, bradycardia, and atrioventricular block 1.

Overall, the administration of amiodarone requires careful consideration of the potential risks and benefits, particularly with regards to its effects on blood pressure. By understanding the mechanisms by which amiodarone causes hypotension, healthcare providers can take steps to minimize this risk and optimize patient outcomes.

From the FDA Drug Label

Hypotension is the most common adverse effect seen with Amiodarone HCl injection. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with amiodarone HCl injection Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose-related, but appeared to be related to the rate of infusion. Amiodarone HCl injection has been reported to produce negative inotropic and vasodilatory effects in animals and humans

Hypotension caused by amiodarone is likely due to its negative inotropic and vasodilatory effects. The exact mechanism is not fully understood, but it appears to be related to the rate of infusion rather than the dose itself. Hypotension is a common adverse effect, occurring in 16% of patients in clinical trials, and is usually seen in the first few hours of treatment 2.

From the Research

Causes of Hypotension

• Amiodarone can cause hypotension due to its vasoactive solvents, particularly in the standard formulation of intravenous amiodarone 3.
• The hypotensive effect of intravenous amiodarone is sustained throughout the maintenance infusion period, and is not solely related to the initial loading dose 4.
• The cosolvents in the formulation of intravenous amiodarone are responsible for the cardiodepressant effects, including hypotension 4.
• Amiodarone-induced hypotension can be severe and refractory, requiring inotropic support and rapid-sequence intubation in some cases 5.

Factors Contributing to Hypotension

• The rate of infusion of intravenous amiodarone can contribute to the development of hypotension, with faster rates increasing the risk 3.
• The use of a new aqueous formulation of amiodarone (Amio-Aqueous) may reduce the risk of hypotension compared to the standard formulation 3.
• The dose of amiodarone may also play a role in the development of hypotension, although the relationship between dose and hypotension is not fully understood 4.

Clinical Implications

• Amiodarone should be used with caution in patients at risk of hypotension, and monitoring of blood pressure is recommended during administration 5.
• The use of amiodarone in patients with pre-existing hypotension or cardiovascular disease requires careful consideration and monitoring 6.
• A deep understanding of the pharmacokinetics and pharmacodynamics of amiodarone is essential for safe and effective use, including management of potential side effects such as hypotension 6.