Pharm 101: Amiodarone

Class

Class III antiarrhythmic

Pharmacodynamics

• Class III antiarrhythmic. Also has class I, II and IV effects
• Primary action:
  • Prolongs action potential duration (and QT interval) due to blockade of rapid component of delayed K current
  • Chronic use also blocks slow K rectifier
• Other effects:
  • Blocks inactivated Na channels. AP prolonging action reinforces this effect
  • Weak adrenergic and Ca channel blocking actions. Causes slowing of HR and AV nodal conduction.
  • Peripheral vasodilation (after intravenous administration)

Pharmacokinetics

• Variable absorption with bioavailability 35-65%
• Bimodal half-life:
  • Rapid component 3-10 days (50% of drug)
  • Slower component of several weeks
• After cessation, drug effects are maintained for 1-3 months
• CYP inhibitor

Clinical uses

• Treatment of atrial and ventricular tachyarrhythmias (SVT, AF, VT, VF)
• Used both to revert VT and prevent recurrence
• ALS algorithm after 3rd cycle of shockable rhythm

Adverse effects

• Acute:
  • Symptomatic bradycardia and heart block in patients with pre-existing sinus or AV nodal disease
  • Hypotension after intravenous administration (due to peripheral vasodilation)
  • Prolongs QT interval, but has low incidence of TdP (< 1%). This is likely due to its broad spectrum of antiarrhythmic actions.
  • Increases the pacing threshold for ICD
• Chronic:
  • Pulmonary fibrosis
  • Deranged LFTs and hepatitis
  • Hypothyroidism (blocks peripheral conversion of T4 to T3) or hyperthyroidism (source of large amounts of inorganic iodine)
  • Skin deposits: photodermatitis and grey-blue discolouration in sun-exposed areas
  • Asymptomatic corneal microdeposits
  • Optic neuritis (rare)

Precautions/contraindications

• Administration in conjunction with other CYP substrates:
  • Increases INR in co-administration with warfarin
  • Increases effect of digoxin
  • Increases concentration of statins

Further Reading

• Nickson C. Anti-arrhythmic Drugs and Cardiac Arrest
• Nickson C. Ventricular Tachycardia