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 10-20mg/kg/day for 7-10 days

·  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

(especially if rapid infusion)

·  Hypotension

·  Bradycardia (resistant to atropine)

·  ↑QTc -> ↑risk torsades de pointes

Tissue toxicity

·  Cirrhosis

·  Pulmonary fibrosis

·  Thyroid disease (hypo > hyper)

·  Corneal disease

 

Feedback welcome at ketaminenightmares@gmail.com