Antiarrhythmic Agents

Question 1

What is the Singh Vaughn-Williams Classification.

Give common examples for each class

Answer 1

Class 1: FAST SODIUM CHANNEL BLOCKERS

• 1A: Prolong action potential (Quinidine)
• 1B: Shortens action potential (Lignocaine)
• 1C: No effect on action potential (Flecainide)

Class 2: BETA BLOCKERS (e.g. metoprolol)
Class 3: K CHANNEL BLOCKERS (Sotalol & Amiodarone)
Class 4: Ca CHANNEL BLOCKERS (Verapamil and diltiazem)

Question 2

What class is Amiodarone (Vaughn-Williams)

Answer 2

Class 3

But also has effects consistent with all three other groups

Question 3

Describe how amiodarone fits into all classes of the Singh Vaughn-Williams classification

Answer 3

CLASS 3
Blocks repolarizing K channel currents in phase 3 of cardiac action potential –> prolonged repolarization –> prolonged refractory period

CLASS 1
Inactivates depolarizing Na channels in phase 0 of cardiac action potential

CLASS 2
Non-competitive beta blocker

CLASS 4
Inhibits L-type Calcium channels

Question 4

List the clinical effects of amiodarone administration

Answer 4

1. Hypotension with rapid IV administration (Polysorbate 80)
2. Delayed conduction AV, His, Purkinje
3. Bradycardia
4. QT prolongation

Question 5

Why does rapid administration of amiodarone cause hypotension?

Answer 5

Due to its excipient: Polysorbate 80.

An excipient is an inactive substance that serves as a medium for a drug included for the purpose of long term stabilization.

Question 6

What is the chemical origin of amiodarone

Answer 6

Iodinated benzofuran derivative

Question 7

Is amiodarone contraindicated in a patient with iodine allergy

Answer 7

No

Question 8

What hormone is amiodarone structurally similar to? What are the implications of this

Answer 8

T3 (Triiodothyroxine)
T4 (Thyroxine)

Implications:
1. Directly interferes with TSH, T3/T4 function
2. Metabolism of amiodarone liberates a vast amount of iodide.
900mg amiodarone gives off 30mg iodide
RDA of iodide = 0.15 - 0.2 mg
This is about 200 x more iodide than recommended daily intake

Question 9

How can amiodarone be administered§

Answer 9

Oral or IV

Question 10

How long after oral amiodarone administration are maximum plasma levels achieved and what is the bioavailability of amiodarone?

Answer 10

4.5 hours

Bioavailability: 20% - 80%. First pass metabolism

Question 11

Describe the preparation of amiodarone

Answer 11

50mg amiodarone
100mg Polysorbate 80 (Hypotension)
20.2 mb benzyl alcohol

Question 12

How is amiodarone administered

Answer 12

Dedicated lumen (not with other drugs)
Diluent: 5% dextrose (not saline)

Emergencies –> peripheral line
Infusions –> central lines preferred: amiodarone is serious acidotic irritant –> phlebitis –> extravasation –> horrific and dysfiguring –>poor anaesthetic candidate for skin grafting (if you’re giving amiodarone..)

Question 13

What is the pKA, Vd and protein binding of Amiodarone

Answer 13

pKa = 6.56
Protein binding: 96%
Vd = 66 - 144 L/kg