Amiodarone is an antiarrhythmic agent with a complex mechanism of action and many effects.
- K+ channel blockade in cardiac myocytes, inhibiting the slow outward current and slowing repolarisation (Class III)
- β-blocker-like activity on SA and AV nodes, decreasing automaticity and slowing nodal conduction (Class II)
- Ca2+ channel blocker-like activity on L-type Ca2+ channels, decreasing the slow inward Ca2+ current, increasing depolarisation time and decreasing nodal conduction (Class IV)
- α-blocker-like activity, decreasing SVR
|Class||Class III antiarrhythmic, though exhibits action from all 4 classes.|
|Uses||VT/VF, resistant arrhythmia, ALS.|
|Presentation||100/200mg tablets, IV: 150mg ampoule to be reconstituted in D5W.|
|Route of Administration||IV/PO.|
|Dosing||IV: Load with 5mg.kg-1 over 1/24, with a further 15mg.kg-1 over the following 24/24 PO: 200mg TDS for 1/52, 200mg BD for 1/52, 200mg OD thereafter.|
|Absorption||Poor PO absorption with bioavailability ~50%.|
|Distribution||Highly protein bound with very high VD of ~70L.kg-1s due to accumulation in fat and muscle.|
|Metabolism||Hepatic metabolism with inhibition of CYP3A4, to the active desmethylamiodarone.|
|Elimination||Very long t1/2 of up to ~55 days. Biliary, skin, and lacrimal elimination, with < 5% of drug eliminated renally. Not removed by dialysis.|
|Resp||10% 3-year risk of pneumonitis, fibrosis, pleuritis.|
|CVS||↓ HR, ↓ BP, ↓ SVR, ↑ QT without risk of TDP. Irritant to peripheral veins.|
|CNS||Mild blurring of vision from corneal deposition, sleep disturbance, vivid dreams, peripheral neuropathy.|
|MSK||Photosensitivity, grey skin.|
|Endocrine||Hyperthyroidism (1%) and hypothyroidism (6%).|
|GIT||Nausea, vomiting, cirrhosis, hepatitis, and jaundice.|
|Other||Amiodarone has potential to cause a number of drug interactions due to its inhibition of CYP3A4 and its high protein binding. A selection include: Digoxin, statins, warfarin, phenytoin, and other antiarrhythmics.
Contraindicated in porphyria.
A mnemonic for some of the rarer effects is BITCH:
- Blue skin
- Interstitial lung disease
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014. Peck and hill
- Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale's Pharmacology. 6th Ed. Churchill Livingstone.