• Need to know PK, PD, SES and adverse effects of amiodarone well.
  1. Class III anti-arrhythmic
  1. Prolongs the APD and therefore, the QT interval mainly by K+ channel blockade.
    • Importantly, it has class I, II and class IV activity as well. This broad spectrum of action accounts for its low risk of TdP despite QT prolongation.
    • Overall, amiodarone’s effects are prolonged AV conduction and decreased automaticity in the Purkinje fibers (β-blockade effect)
    • It also slows the sinus rate (CCB effect)
    • Amiodarone also has α-blockade effect, causing vasodilation and hypotension.
  1. PO and IV
    • PO absorption can be erratic.
    • The oral bioavailability is 35-65%, due to first pass metabolism.
  1. Strongly protein bound, T½ of 20-100 days. Very large Vd.
  1. Amiodarone is hepatically metabolized to desethylamiodarone. This metabolite is bioactive.
  1. Rapid component is 3-10 days (50% of the drug is eliminated here)
    • Slower component over several weeks.
    • After discontinuation, drug effects may still be seen for 1 to 3 months.
  2. Elimination is by hepatobiliary system.
  1. Termination of both atrial and ventricular tachyarrhythmias.
    • Prevents recurrent VT/VF, may be used to revert VT/VF.
    • Used in the third cycle of shockable ACLS rhythm.
  1. Severe hypotension
  2. Bradycardia
  3. Thyroid dysfunction
  4. Breast feeding
  1. Amiodarone is a CYP450 enzyme inhibitor. Therefore
    • It increases the effect of digoxin, warfarin and statins.
  2. Because it is cleared by hepatic CYP system, other inhibitors, e.g. cimetidine will increase its effect. Also, inducers, e.g. rifampicin, will reduce its effect.
  3. Because it is an anti-arrhythmic, it potentiates other anti-arrhythmics, e.g. procainamide, phenytoin, quinidine and flecanide.
Special precautions
Adverse effects
  1. Acutely – causes bradycardia (especially those with pre-existing SA and AV node disease) and hypotension (due to vasodilation)
  2. Chronic – pulmonary fibrosis (most significant adverse reaction), photodermatitis, thyroid dysfunction (both hypo and hyperthyroid), hepatitis/abnormal LFTs and optic neuritis.
Withdrawal states
Special notes