Amiodarone

 

Although a "dirty drug" with multiple mechanisms of action, amiodarone is my favourite anti-arrhythmic because it’s almost never wrong – and thus has landed itself a role in the ARC guidelines as a first line anti-arrhythmic in an arrest situation.  Watch out for the hypotension that really does happen if you push in a loading dose too quickly!!

 

For

•      tachyarrhythmias (VT, VF, AF, atrial flutter, WPW)
•      VF resistant to DCR (first line therapy)

 

Dose

•         300 mg in 20mL 5% dextrose (in minijet) over 1 – 2 minutes if peri-arrest (follow with further 150 mg if  initial dose ineffective)
•         5 mg/kg (300 mg) load (in 250 mL 5% dextrose) over 20 - 120 mins, followed by 15 mg/kg (in 500 mL 5% dextrose in glass with non-PVC giving set) IV over next 24h
•         conversion to oral dosing may occur early on (some recommend overlapping oral and IV treatment by 2 days) but will require ongoing loading (200 – 400 mg TDS for one week, 200 mg BD for one week then continue at 200 – 400 mg daily) as drug has very long half life

 

Pharmaceutics

Amiodarone is an iodinated benzofuran derivative and a structural analogue of thyroid hormone.  It is available as tablets (100 – 200 mg) and as a solution (150 mg ampoule) which should be made up with 5% dextrose and non-PVC if it is to run over >60 mins. Not compatible with saline.

 

Pharmacokinetics

•         poorly absorbed from GIT – oral bioavailability of 50 – 70%
•         highly protein bound (>95%), Vd 2 – 70 L /kg
•         long elimination half life. Hepatic metabolism to desmethylamiodarone fe (27 – 107 days) which has some anti-arrhythmic activity)
•         excreted lacrimal glands, skin and biliary tract
•         therapeutic range 1 – 2.5 mg/L, monitoring levels not generally helpful as toxicity can occur in therapeutic range

 

Pharmacodynamics

Mechanism of action

•    Class III (and Ic, II, IV) anti-arrhythmic activity
•    Class I – Na⁺ channel blockade
•    Class II – b adrenoceptor blocker (weak)
•    Class III – K⁺ channel blockade
•    Class IV – Ca⁺⁺ channel blockade
•    Decreases SA node and junctional automaticity, slows AV and bypass tract conduction, prolongs refractory period

 

Precautions

•         all anti-arrhythmics are pro-arrhythmogenic – does the patient require the drug?? Interacts with other anti-arrhythmics – particularly prone to cause bradycardia, arrest or even VF with metoprolol or propranolol, other b blockers/ Ca⁺⁺ channel blockers/ drugs that delay AV condition
•         INCREASED RISK OF SEVERE CARDIAC DYSFUNCTION INCLUDING DYSRHYTHMIA for patients on amiodarone exposed to inhalational anaesthetic agents
•          drug interaction due to high protein binding eg with warfarin, digoxin, phenytoin etc.
•          porphyria

 

Side effects

•   relate to multiple sites of action
•   pulmonary – pneumonitis, fibrosis, pleuritis, bronchospasm, ARDS – 10% of patients develop fibrosis by 3y, 10% mortality (high FiO2 potential risk factor for acute pulmonary toxicity in critically ill).  There tend to be two presentation patterns; 1: progressive breathlessness with a slow infiltration on CXR following prolonged treatment or 2: acute inflammatory disorder which presents with cough and hypoxia with breathlessness (Dxx pneumonia) tends to respond to cessation of drug and corticosteroids.  Reversibility is variable.
•    thyroid toxicity – hyperthyroidism 0.9%, hypothyroidism 6% (disturbances due to high iodine content of the drug), prevents peripheral conversion T4 àT3
•     liver – cirrhosis, hepatitis and jaundice, LFT pre and during long term therapy, hepatic dysfunction leads to accumulation of the drug.
•     cardiac – bradycardia and hypotension when given rapidly (due to non-competitive inhibition of a and b receptors which are also blocked by volatile agents), low arrhythmic potential, prolongation of QT interval can occur.
•      eyes – corneal micro deposits causing reversible minor visual halos/blurred vision are common. Rarely optic neuropathy may occur.  Patients on long term therapy need annual ophthalmic examination
•      GI – metallic taste, GI upset.
•      neurology – peripheral neuropathy, rarely myopathy, headache, sleep disturbance.
•      skin – photosensitivity, slate-grey discolouration (irreversible), allergic skin rash
•      other – thrombocytopaenia, decreased libido, alopecia

 

Contraindications

•          iodine hypersensitivity
•          pregnancy and lactation.
•          thyroid dysfunction
•          risk of bradyarrhythmias, may require permanent PM insertion.

          

Monitoring for administration

•          monitor BP and ECG
•          before commencing, ECG, U&E, LFT, TFT, RFT and CXR. Repeat every six months. TFT may become deranged for 3 months after ceasing treatment, liver damage may develop up to a year after stopping treatment.