G7iii / 21B11 / 16A11: Provide a detailed account of the side effects of Amiodarone

21B11: Exam Report

Provide a detailed account of the side-effects of armiodarone

17% of candidates passed this question.

The question asked for a detailed account of the side effects of amiodarone, hence those candidates that just provided a list or outline scored less well. It was expected that candidates provide some detail of the side effect. Answers that scored well prioritised those relevant to ICU clinical practice. Many provided disorganised outlines of the side effects and frequently the cardiovascular side effects were poorly explained. Many candidates omitted the important drug interactions of amiodarone use and few candidates related the side effect profile to the duration of treatment.

16A11: Exam Report

Provide a detailed account of the side effects of Amiodarone.

26% of candidates passed this question.

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.

G7iii / 21B11 / 16A11: Provide a detailed account of the side effects of Amiodarone

CVS

  • Irritant to veins
  • Bradycardia → resistant to atropine
  • Prolongs QT → risks TdP
  • Potent VD → risks cardiovascular collapse → esp. with rapid IV bolus
  • Complete AV block

Resp

  • Pulmonary fibrosis secondary to alveolitis
  • Pulmonary toxicity is dose-related → esp. >400mg/day for >4wks

CNS

  • Sleep disturbance
  • Headache
  • Peripheral neuropathy
  • Tremors/proximal skeletal m. weakness

Ocular

  • Corneal microdeposits → virtually all patients
  • Halo development in peripheral fields
  • Optic neuritis may progress to blindness

Dermatologic

  • Blue slate skin
  • Photodermatitis esp. to sun-exposed areas

GI

  • Fatty infiltration of liver
  • ↑transaminases
  • Hypersensitivity hepatitis

Endocrine

  • 5% pats → hyper/hypo-thyroidism
  • More likely with pre-existing thyroid disease
  • Hyperthyroidism → from release of iodine during metabolism
  • Hypothyroidism → when Ami inhibits peripheral deiodination of T4 → T3

Pregnancy

  • Amiodarone & its metabolite demethylamiodarone (DEA) are found in placenta & breast milk
  • Can cause infant hypothyroidism

Drug Interactions

  • Displaces drugs from plasma proteins 2° large PPB
  • ↑plasma [ ] of other antiarrhythmics; DIGOXIN, PROCAINAMIDE, PROPANOLOL, VERAPAMIL
  • Plasma digoxin x 50%
  • Amiodarone is a substrate for CYP3A4
  • ∴ drugs inhibit CYP3A4 = ↑ plasma amiodarone
  • e. H2 blocker cimetidine
  • Drugs which induce CYP3A4 ↓amiodarone e. rifampicin
  • Amiodarone inhibits P450 enzyme & ↑levels of drugs: statins, digoxin, warfarin
  • WARFARIN needs to ↓ 1/3 of dose with amiodarone
  • Erythromycin → also prolongs QT interval = ↑risk TdP

Author: Krisoula Zahariou