CLASS 3 ANTIARRHYTHMIC
Supra ventricular & Ventricular Arrhythmias
AF, VT, VF
- Prolongs phase three of the cardiac action potential (8-24h) - increasing refractory period via Na & K channels.
- Also has all class 4 electrophysiological properties
- Beta blocker/Calcium Channel Blocker effects on SA & AV node (rapid IV)
- Slows intracardiac conduction of action potential via sodium channel
- There is a resulting decrease in heart rate and in vascular resistance.
- A slower HR allows for diastolic coronary flow to improve and prevents tachy-related ischaemia - Increases duration of ventricular and atrial muscle; inhibiting Na,K-activated myocardial ATP-ase.
Little negative inotropic activity, and little chance of pro-arrhythmias = advantageous for use in patients with heart failure
Chemically resembles thyroxine (T4), and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic actions
(am-IOD-arone = iodine)
Oral Bioavailability = 22 to 95%
- Amiodarone is extensively metabolized in the liver by cytochrome P450 3A4.
- Interacts with digoxin, warfarin, phenytoin, and others.
- Major metabolite of amiodarone is desethylamiodarone (DEA)
- DEA has antiarrhythmic properties.
- Metabolism is inhibited by grapefruit juice.
- Do not use with Simvastatin >20mg = can cause rhabdomyolysis.
- Hepatic and biliary excreted.
- Almost no urinary excretion and drug is not dialysable.
- Elimination half-life average of 58 days.
IV and oral amiodarone have different electrophysiological properties and it may be possible to administer i.v. amiodarone to cardiovert AF in patients who are already on chronic oral treatment.
Most toxicity of amiodarone is dose-dependent and related to chronic treatment; however, it should be used with caution in patients with acute ischaemia or myocardial dysfunction, as profound hypotension may be induced by i.v. or
high-dose oral loading.
Adverse effects will occur in 15 to 50% of patients, from the first year of treatment to prolonged treatment with amiodarone, up to 5%of which will experience pulmonary toxicity (interstitial disease, lung mass or distress). Altogether, 20% of patients will need to discontinue amiodarone. Semi-annual thyroid hormone transaminase tests, an annual chest x-ray as well as an annual ECG are recommended in all amiodarone patients.
(Hypothyroidism 20% can occur & liver cirrhosis <3%)
There is evidence that Magnesium Sulphate can be used synergistically with amiodarone to prevent arrhythmias*
S/E's = hypotension, bradycardia and peripheral phlebitis.
Contraindications to IV amiodarone are bradycardia, senoatrial block, severe disturbance of conduction & 2nd/3rd AV block
Also CI's incl hypotension, severe respiratory failure, hepatocellular failure and hyperthyroidism.
Should not be used with polymorphic VT as it associated with a prolonged QT interval which is made worse with antiarrhythmic drugs.
QT interval represents electrical depolarization and repolarization of the ventricles.
- Statins = (Simvastatin >20mg can cause rhabdomyolysis)
- Class I anti arrhythmic agents (sodium channel blockers -
LA's, propafenone, flecanide, phenytoin)
- Other drugs which contribute to prolong QT interval, digoxin,
oral anticoagulants and general anaesthesia.
Dr. David Lyness
Initially 5 mg/kg over 20–120 minutes with ECG.
Then inf. if necessary according to response up to max. 1.2 g in 24 hours.
Give amiodarone 300 mg IV after 3 shocks;
Regardless of whether they are consecutive shocks, or interrupted by CPR, or for recurrent VF/pVT during cardiac arrest.
Consider a further dose of amiodarone 150 mg IV after a total of five defibrillation attempts.