Outline the pharmacology of amiodarone.
This was a repeat question and was generally answered well. Some candidates lost marks for
being too approximate on the pharmacokinetics.
It is ironic that the examiners might complain about a lack of detail by writing a two-line comment. To avoid being too approximate, the answer here should contain a satisfying number of precise measurements.
| Class | Class III antiarrhythmic |
| Chemistry | Iodinated benzofuran |
| Routes of administration | Oral and IV |
| Absorption | Slow erratic GI absorption (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 |
| Target receptor | Mainly potassiu (Ikr) channels, but also voltage gated calcium channels, beta and alpha adrenergic receptors, and L-type calcium channels |
| 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 |
| 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). Prolonged AV node refractory period, slowed conduction along His and Purkinje system, bradycardia, QT prolongation, many other side effects (skin discolouration, hypothyroidism, cataracts, hepatitis) |
| Single best reference for further information | Hamilton et al (2020) |
Kowey, Peter R., et al. "Intravenous amiodarone." Journal of the American College of Cardiology 29.6 (1997): 1190-1198.
Andreasen, F. H. P. H., et al. "Pharmacokinetics of amiodarone after intravenous and oral administration." European journal of clinical pharmacology 19.4 (1981): 293-299.
Gough, William B., et al. "Hypotensive action of commercial intravenous amiodarone and polysorbate 80 in dogs." Journal of cardiovascular pharmacology 4.3 (1982): 375-380.
Hamilton, David, et al. "Amiodarone: a comprehensive guide for clinicians." American Journal of Cardiovascular Drugs (2020): 1-10.
van Erven, Lieselot, and Martin J. Schalij. "Amiodarone: an effective antiarrhythmic drug with unusual side effects." Heart 96.19 (2010): 1593-1600.