Amiodarone

Classification:

• Class III – Potassium (K⁺) channel blockers
• Amiodarone – the most effective anti-arrhythmic drug, but associated with the highest rate of adverse effects.
• Dronedarone – similar to amiodarone, but less potent and associated with fewer adverse effects.
• Sotalol – also a non-selective beta-blocker.
• Ibutilide – may be used for acute cardioversion of pre-excited atrial fibrillation (AF).

Mechanism:

• The most effective anti-arrhythmic drug, but associated with the highest rate of adverse effects
• Predominantly exhibits Class III properties, but also Class I, II, and IV effects
• Prolongs the effective refractory period (ERP) in atrial and ventricular myocardium
• Reduces excitability and automaticity and prevents re-entry
• Slows the SA node and prolongs conduction through the AV node
• Slows conduction in the conduction system and working myocardium
• Has a vasodilatory effect on vascular smooth muscle
• Minimal reverse use-dependence

Effect on AF:

• Maintenance of sinus rhythm – prevents recurrence of AF episodes
• Cardioversion of AF to sinus rhythm – termination of an AF episode and restoration of sinus rhythm

Volume of distribution of amiodarone

• Amiodarone has a large volume of distribution, which means that it
• accumulates in all tissues, especially those rich in fat, and is then slowly released:
• adipose tissue, lungs, liver, thyroid gland, myocardium, cornea, skin
• Due to its large volume of distribution, its pharmacokinetics differ markedly from other anti-arrhythmic drugs.

Amiodarone loading (10 g)

• The principle of long-term oral amiodarone therapy is that the effect becomes apparent only after a total cumulative dose of 10 g has been administered.
• It does not matter whether the cumulative 10 g dose is achieved orally or intravenously.
• Loading is usually initiated intravenously in hospital (e.g. 3 g) and then continued orally at home (7 g).
• 1200 mg is the maximum daily dose of amiodarone (intravenous + oral).
• The chronic maintenance dose is 200 mg once daily.

Patient monitoring before and after initiation of amiodarone:

• Before initiation – comprehensive evaluation focused on the thyroid gland, eyes, lungs, heart, and liver,
• because amiodarone is associated with numerous adverse effects
• Discontinue or reduce the dose if adverse effects occur

Amiodarone is the most effective anti-arrhythmic drug but is associated with the highest rate of adverse effects due to tissue accumulation.

• Administration of amiodarone for more than 12 months is not recommended.

Adverse effects – may occur after 1–2 months of amiodarone therapy:

• Thyroid:
  • Hypothyroidism (2–10 %)
  • Hyperthyroidism (1–10 %)
• Lungs:
  • Pulmonary fibrosis (1–17 %)
  • Interstitial pneumonitis (5–10 %)
  • ARDS (< 2 %)
• Liver:
  • Elevated liver enzymes (15–50 %)
  • Hepatitis (< 1 %)
  • Hepatic necrosis (< 1 %)
• Heart:
  • Hypotension (> 10 %)
  • QT interval prolongation (1–10 %)
  • Bradycardia (2–5 %)
  • Torsades de pointes (< 1 %)
  • AV block (< 1 %)
• Eyes:
  • Corneal deposits (98–99 %)
  • Optic neuropathy (< 1 %)
  • Blurred vision (1–10 %)
• Skin:
  • Photosensitivity (10–75 %)
  • Blue-grey skin discoloration (8 %)
  • Stevens–Johnson syndrome (< 2 %)
• Neurological effects:
  • Ataxia, tremor, peripheral neuropathy (2–20 %)
  • Fatigue, insomnia, dizziness (1–10 %)
• Gastrointestinal:
  • Nausea, constipation, loss of appetite (5–10 %)
  • Vomiting (> 10 %)
  • Diarrhoea (< 2 %)
• Kidneys:
  • Renal impairment (< 2 %)

Amiodarone and dronedarone both belong to Class III anti-arrhythmic drugs but differ in their properties.

• Amiodarone is more effective for maintenance of sinus rhythm,
• whereas dronedarone is less potent but associated with fewer adverse effects.