amiodarone

see also:

• pharmacology main index
• anti-arrhythmic agents
• WH policy - amiodarone infusion (docx) - intranet only

• type 3 V-W anti-arrhythmic agent which also has some noncompetitive alpha adrenergic blockade as well;
• commonly used in Rx of many arrhythmias including VT, AF

• primarily a class III antiarrhythmic agent but also:
  • sodium channel blockade (class I activity)
  • mild beta blocking action (class II activity)
  • some calcium channel blockade (class IV activity)
• directly decreases sinus node and junctional automaticity
  • dose dependent atropine resistant bradycardia
• slows atrioventricular (AV) conduction
• slows abnormal bypass tract conduction
• prolongs refractory period of myocardial tissues (atria, ventricles, AV node and bypass tracts)
• but does not significantly depress the spontaneous diastolic depolarisation of Purkinje fibres
• prolonged QRS and QTc
• may cause U waves and changed T waves on ECG
• strong anti-fibrillatory action
• increases coronary blood flow
• reduces myocardial oxygen consumption without altering cardiac output
• antagonistic to catecholamines and sympathomimetic agents without causing ß-adrenergic blockade

• cardiac conduction blocks unless functioning pacemaker in situ
• bradycardia
• hypotension
• lactation
• pregnancy - class C drug
• care with use of other cardiac drugs such as digoxin, anti-arrhythmics
• PH thyroid disorders is a precaution for ongoing Rx

• 5mg/kg iv up to max. 300mg in a large vein to avoid tissue necrosis from extravasation
  • administer with 100ml 5% dextrose over 20-30min if time allows, or,
  • administer with 20ml 5% dextrose over 1-2min ivi if unstable life threatening rhythm such as sustained VT or VF (after 3rd defibrillation attempt) and if unhelpful a further dose of 150 mg IV over 1 -2 minutes may be given

• maintenance infusions must be administered using glass bottles and given with 5% dextrose
• 15-20 mg/kg bodyweight (usually 900mg) given over 24 hours
• max. 1200mg in 24hrs

• load dose 200-400mg tds for 1wk, then
• 200-400mg bd for 1wk, then
• 100-200mg daily

• hypotension
• symptomatic bradycardias
• prolonged QTc and risk of torsade de pointes VT

• common & increase markedly after 1st yr of use when 75% will have adverse effects!
• symptomatic pulmonary toxicity in 10-15% > 1yr use → death in 10% of those affected
• hepatic injury common but rarely fatal
• aggravation of arrhythmia in 2-5% pts
• asymptomatic corneal microdeposits in all
• cutaneous photosensitivity 10-15%
• blue discoloration 5%
• symptomatic hypothyroidism 5% & hyperthyroidism 2% (inhib. periph. T4 → T3);
  • NB. each amiodarone 200 mg tablet contains organic iodine approximately 75 mg and, in the steady state, metabolism of amiodarone 300 mg yields iodine 9 mg/day, well in excess of the highest normal dietary intake
• substantial increased LDL-cholesterol occurs frequently

• ⇒ increased plasma concentration of:
  • digoxin, warfarin, quinidine, procainamide, phenytoin, diltiazem, encainide, flecainide;
• ⇒ increased risk of:
  • bradycardia, sinus arrest or AV block if concurrent beta adrenergic blockers or calcium channel blockers
• drug interactions may persist for weeks despite cessation of amiodarone;