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Amiodaraone mechanism of actions Also how it causes hypothyroidism

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Amiodarone: mechanism of action

Amiodarone is mainly a Class III antiarrhythmic, but it has actions from all four Vaughan-Williams classes:
  • Blocks K⁺ channels - its dominant effect. This prolongs phase 3 repolarization, action-potential duration, and the effective refractory period in atrial and ventricular myocardium.
    • ECG effects: prolonged QT interval.
  • Blocks Na⁺ channels - slows phase 0 depolarization and conduction.
  • Blocks Ca²⁺ channels - slows conduction through the AV node.
  • Noncompetitive beta-blocking and alpha-blocking effects - reduces SA-node automaticity and slows AV-nodal conduction.
So, in short: it suppresses automaticity, slows conduction, and prolongs refractoriness, helping prevent both atrial and ventricular tachyarrhythmias. This mixed-channel action is why it is useful in atrial fibrillation and resistant ventricular arrhythmias.
Lippincott Illustrated Reviews: Pharmacology, p. 401.

Why does it cause hypothyroidism?

Amiodarone is iodine-rich and structurally related to thyroxine. It is about 37% iodine by weight. Metabolism releases a large iodine load into the circulation.

Main mechanism: persistent Wolff-Chaikoff effect

  1. Excess iodine enters the thyroid.
  2. The thyroid normally responds by temporarily reducing iodine organification and thyroid-hormone synthesis. This is the Wolff-Chaikoff effect.
  3. Most healthy thyroid glands then “escape” this suppression after a short period.
  4. Some patients, especially those with pre-existing thyroid disease, cannot escape.
  5. Therefore, T4 and T3 synthesis remains suppressed, leading to:
    • ↓ Free T4 eventually
    • ↓ T3
    • ↑ TSH
    • Clinical hypothyroidism

Additional contribution

Amiodarone inhibits type 1 5′-deiodinase, reducing peripheral conversion of T4 to active T3. This contributes to low T3 and increased reverse T3. It also alters thyroid-function tests even without true hypothyroidism.

Who is at higher risk?

  • Patients in iodine-sufficient regions
  • Women
  • Those with Hashimoto thyroiditis
  • Positive anti-TPO antibodies or other underlying autoimmune thyroid disease
Hypothyroidism may persist after stopping amiodarone because the drug has a long half-life and is stored extensively in tissues.
Tietz Textbook of Laboratory Medicine, 7th Edition, pp. 3826-3831; Goldman-Cecil Medicine, pp. 2788.
One-line exam answer:
Amiodarone causes hypothyroidism mainly through its large iodine load, which produces a persistent Wolff-Chaikoff effect in susceptible thyroid glands, inhibiting iodine organification and thyroid-hormone synthesis; it also inhibits peripheral T4-to-T3 conversion.
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