| Class | Class III antiarrhythmic |
|---|---|
| Chemistry |
Iodinated benzofuran |
| Routes of administration |
Oral and IV |
| Absorption |
Slow erratic GI absoprtion (slow onset when given orally, ~ 4.5 hrs to peak effect). Bioavailability = 20-80% |
| Solubility |
Highly lipid-soluble and poorly soluble in water; pKa = 6.56 |
| Distribution |
Extensively distributed to the tissues - VOD is about 66 L/kg. 96% protein bound |
| Metabolism |
Hepatic metabolism by CYP3A4; main metabolite is desethylamiodarone, which is pharmacologically active |
| Elimination |
Distributes widely, particularly into adipose tissue and lung. Elimination is extremely prolonged in chronic therapy, in excess of 100 days. Half-life is 29 days. |
| Time course of action |
Onset of action is delayed because of the redistriution, and maximum effect (especially the Class I and Class IV effects) may take weeks to develop |
| Target receptor |
Mainly potassium (Ikr) channels, but also voltage gated calcium channels, beta and alpha adrenergic receptors, and L-type calcium channels |
| Mechanism of action |
Blocks repolarising potassium currents in Phase 3 of the cardiac action potential prolonging the repolarisation. Also decreases the velocity of Phase 0 by its Class I effect, and acts as a noncompetitive beta-blocker, and inhibits L-type calcium channels. |
| Clinical effects |
Hypotension with rapid IV administration, which is due to its IV excipient (polysorbate 80). |
| Literature reference |
Hamilton et al (2020) |
| CICM details of understanding | Level 1 |
| Mentioned around Deranged Physiology |
Amiodarone gets its own chapter of course, because we both love and fear it. by that extension, Classification of antiarrhythmic agents. Often a sub-trope of synergy and toxicity in antiarrhythmic polypharmacy. |
| Related SAQs |
They just won't stop with the amiodarone: Question 19 from the first paper of 2024 Question 11 from the second paper of 2021 Question 2 from the second paper of 2018 Question 11 from the first paper of 2016 Question 13 from the second paper of 2014 Question 22 from the second paper of 2010 Question 5 from the second paper of 2008 |