Amiodarone Flashcards
What is the class and chemistry of amiodarone
Class III antiarrhythmic (Vaughn-Williams)
(But action in all classes)
Chemistry: Iodinated benzofuran
Striking chemical resemblance to thyroid hormones
- -> interefere with TSH, T3 and T4 activity
- -> Metabolism –> additional iodide ions (200 x RDA for iodine)
What are the uses of amiodarone
- Refractory VF
- Ventricular tachycardia
Chronic prevention in patients prone ventricular arrhythmias who have decreased LV function (so they can go 5 minutes without being slammed with an AICD charge) - Acute onset atrial fibrillation
–> BB C/I + Digoxin vagatonic effects will be ineffective, amiodarone is the treatment of choice - Chronic AF (3rd or 4th line)
Presentation and preparation of amiodarone?
Amiodarone 50 mg
Polysorbate 80 100mg –> causes hypotension during fast infusion
Benzyl alchohol 20.2 mg
Which component of the amiodarone preparation causes hypotension. Where else is this compound found
Polysorbate 80 (1oo mg per 50 mg amiodarone
This substance is also found in ice cream and eye drops. However, the speed and dose with which it is administered with amiodarone causes hypotension
Summarise the mechanism of action of amiodarone with respect to the Vaughn-Williams classification
Vaughn Williams:
Class 1 effect:
- -> V gated Na channels blocked (especially inactivated channels in ischaemic tissue)
- -> Reduced velocity phase 0
Class 2 effect:
- -> Interferes with adenylate cyclase regulation –> reduced cAMP.
- -> It does not compete with the beta receptor ligands but rather interferes with the second messenger system
Class 3 effect:
–> Repolarising K channel blockade –> slows rate of repolarisation –> prolonged refractory period (prolonged QT) (prolonged phase 3)
Class 4 effect:
–> Non-selective L-type CCB effect analagous to verapamil and diltiazem
How is amiodarone administered
Oral - with meals and divide dosing if GI upset
IV (Depends on indication)
For Tachydysrrthymia
- Total dose: 15mg/kg over 24 hours
- Loading dose: 5mg/kg over 20 mins to 2 hours (1 hour)
For cardiac arrest:
- 300 mg IV
- then 150 mg IV
Describe the onset and duration of action
Onset is delayed due to extent of redistribution. Maximum effect may take weeks to develop
Why is it better to give amiodarone via a central venous cannula?
Because it is a serious acidic irritant
pH despite dilution of 900 mg in 500ml D5W can be 4.14 - 4.65.
Extravasation injuries can be horrific and disfiguring
In what should amiodarone be diluted prior to adminstration
D5W
Describe amiodarone’s intestinal absorption
Slow: takes 4.5 hours to achieve max plasma levels in healthy volunteers
Oral bioavailability: 20 - 80% (variable)
Some drug is lost to a very random first pass effect
What is amiodarone’s elimination half life. Explain why
Its elimination half life is 29 days
–> It binds everywhere to everything
Protein bound: 96%
Highly lipid soluble
Vd = 66 - 144 L/kg
How is amiodarone metabolised. Describe relevant metabolites and their characteristics
Liver –> CYP3A4: oxidative deethylation
Metabolite: desethylamiodarone (is active as amiodarone with a longer half life and greater tissue binding)
Summarise he clinical effects of amiodarone
RAPID INFUSION
- Hypotension: Polysorbate 80 induced reduced myocardial contractility
ACUTE USE
- Delayed AV conduction (Class 2 and 4 effects)
CHRONIC USE (Class 1a and 3 effects)
- Prolonged repolarisation (and prolonged QT)
- Prolonged AP duration –> decreased re-entry
- Increased risk of early afterdepolarizations
- minimal effect QRS
What are the contraindications of amiodarone
Absolute
1. Iodine allergy
Relative
- Already prolonged QT
- AF unknown duration
- Known atrial appendage thrombus
- 2nd or 3rd degree heart block
- Severe hyperthyroidism/hypothyroidism
What are the side effects of amiodarone with regard to its short term use - in the ICU
Minimal
It has mild vasodilator and negative inotropic effects which tend to get lost in the positive haemodynamic consequences of controlling rhythm and rate.
Polysorbate 80 related hypotension is seldom seen as it is not administered fast enough for hypotension to develop.
Side effects are only vary rarely seen in the acute setting. This is different to chronic use.
