2016A09 Describe the mechanism of action, pharmacokinetics and major side effects of amiodarone.

 

List:

·      PC

·      PK

·      PD

 

Physicochemical:

Structure

·   Iodine-containing

·   Similar appearance to thyroxine

Presentation

·   Tablets

·   Aqueous solution

 

Pharmacokinetic:

Administration

·   Arrest 300mg push

·   IV loading 150mg 1/24 then 850mg 23/24

·   PO loading 50mg/kg/day for 3/7

·   Maintenance: ~100-200mg daily

Time course

·   IV onset 5 minutes

·   IV duration 30 mins for bolus

Absorption

·   Variable

Distribution

·   VD 70L/kg

·   Plasma protein binding >95% (can displace other highly bound drugs e.g. warfarin)

·   Tissue protein binding very high

·   Lipid solubility high

Metabolism

·   Hepatic CYP

·   Cl 1.5-11mL/kg/min

·   t1/2β 15-140 days

·   Active metabolite desethylamiodarone

Excretion

·   Bile, skin, tears

 

Pharmacodynamic:

Antiarrhythmic class

·   Broad spectrum: class 3 > 1,2,4

·   ↓K+ rectifier conductance -> prolongs phase 3 of ventricular action potential

Use

·   Ablation of supraventricular and ventricular tachyarrhythmias

·   Rate control in AF

CVS toxicity

·   Hypotension, bradycardia if rapid bolus

·   ↑QTc -> ↑risk torsades de pointes

Tissue toxicity

·   Cirrhosis

·   Pulmonary fibrosis

·   Thyroid disease (hypo > hyper)

·   Corneal disease

 

 

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