Question 11

College Answer

The question asked for a detailed account and the expected marks were spread across a 
range of systemic side effects, not just the cardiovascular and pulmonary side effects. Many 
candidates provided irrelevant and lengthy descriptions of the mechanisms of action of 
amiodarone which was not asked for in the question and gained no additional marks. Most 
successful answers used an organ systems approach to include the many side effects of 
amiodarone.
Many candidates failed to mention skin side effects, neurological side effects, GI/hepatic side 
effects, pregnancy and breast feeding considerations, and interactions with other highly protein 
bound drugs. The predominant mechanism for hypotension with rapid IV administration of 
amiodarone was incorrectly given in a number of answers.

Discussion

"Provide a detailed account" is a strange instruction for a 10-minute answer. One can be sure that they meant "write a point form list of everything you can think of", because detailed accounts are harder to mark. 

• Cardiac:
  • Bradycardia (5%)
  • Torsades de pointes (<1%)
  • Hypotension with rapid IV administration (due to polysorbate 80)
• Pulmonary
  • Pulmonary fibrosis (1.6%)
• Dermatological
  • Photosensitivity (25-75%)
  • Blue skin discolouration (<10%)
• Ophthalmic
  • Corneal deposits and cataracts (100%)
  • Optic neuritis (<1%)
• Thyroid
  • Wolff-Chaikoff effect: iodine-induced hypothyroidism (1-23%)
  • Hyperthyroidism can also occur (1-32%)
• Hepatic
  • LFT derangement (15%)
  • Hepatitis and cirrhosis (<3%)
• Neurological
  • Ataxia, tremor, peripheral neuropathy
  • Sleep and memory disturbances
• Urogenital
  • Epididymitis
• Pharmacokinetic
  • By binding to albumin and other protein, amiodarone can displace other highly protein-bound drugs, and increase their free fraction (increasing their effect)
• Obstetric
  • Penetrates the placenta, causing iodine overload and hypothyroidism of the foetus, causing neurodevelopmental abnormalities
  • Excreted into breast milk

That "predominant mechanism for hypotension with rapid IV administration" the college examiners are referring to is probably the haemodynamic effect of polysorbate 80, an excipient which is present in high conentrations in each amiodarone ampoule (there is 100mg polysorbate per every 50mg of amiodarone).   Gough et al (1982) found that it is responsible for the hypotension one can sometimes see when giving amiodarone quickly (their specific dog experiment delivered 5mg/kg over 5 minutes, which is probably faster than most human applications).

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.