Antiarrhythmic Drugs

Under class I drugs, which subclasses block sodium channels the most to the least?

IC > IA > IB

Under class I drugs, which subclasses block postassium channels the most to the least?

Most: IA (prolongs QT interval)

Middle: IC

Least: IB (decreases QT interval)

Which Class I drugs display use-dependence? Which Class I drugs display reverse use dependence?

Use-dependence: enhanced drug binding at rapid rates (bc Na+ spends more time in open or inactivated state) — Class

Reverse use dependence: enhanced drug binding at lower rates — Class

Flecainide and Propafenone drug class

Class 1C drugs

Class 1C drug MOA and effect on action potential duration

• Strong Na+ blocker

• Mild K+ blocker

• No effect on AP duration/QT interval

Class 1B drug MOA and effect on action potential duration

• Weak Na+ blocker

• Decreases AP duration/QT interval

Class 1A drug MOA and effect on action potential duration

• Moderate Na+ blocker

• Moderate K+ blocker

• Increases AP duration/QT interval

Flecainide and Propafenone (Class 1C) adverse effects

Metallic taste, constipation, tremor, visual complaints

What Class I drug subclass is used most often?

Class 1C (flecainide, propafenone)

Drug class of lidocaine and mexilitine

Class 1B

Class 1B adverse effects

Dose-related GI (Mexilitine) and neurologic side effects, like tremor (both Lidocaine and Mexilitine)

Quinidine, procainamide, disopyramide drug class

Class 1A

Quinidine adverse effects

• cinchonism: headache, hearing/vision loss, tinnitus, psychosis and cognitive impairment

• N/V/D

• thrombocytopenia

Procainamide adverse effects

• Drug-induced lupus erythematosus (reversible)

• N/V/D

• agranulocytosis (severely low neutrophil levels)

Class 1A drugs contraindications

Avoid drugs that prolong QT

Toxicity of class 1 drugs

Prolongation of QRS duration (due to Na+ blockage/prolonged depolarization) → cardiac side effects

Class II drugs MOA

Beta blockers that slow down heart rate by decreasing the pacemaker current (phase 4) in SA nodal cell

1st generation beta blockers (Propranolol, nadolol, timolol) MOA

block both β1and β2 receptors — non-selective

2nd generation beta blockers MOA

block only β1 receptors and are considered “cardio-selective.”

3rd generation beta blockers (i.e. labetolol, carvedilol) MOA

block both β1and β2 and α receptors and are considered “vasodilators”

What generation beta blocker is used primarily in congestive heart failure?

3rd generation — labetolol, carvedilol

Class II drugs/beta blockers toxicity/adverse effects

• Bradycardia

• Hypotension

• Bronchospasm

• Cold extremities

• Impotence

• decreased myocyte contractility

• Insomnia, depression

Class III drugs MOA

K+ channel blockers → prolong QT interval/action potential duration

T or F: Class III drugs (K+ channel blockers) have reverse use dependency

True!

They bind more tightly/have more pronounced effects with slower HR

Drug class of Amiodarone, dronedarone, sotalol, dofetilide, ibutilide

Class III drugs/K+ channel blockers

Adverse effects of sotalol, dofetilide, and ibutilide (class III)

Torsades de pointes

Contraindications of sotalol, dofetilide, and ibutilide (class III)

Processes that increase vulnerability to torsades de pointes:

• Ventricular hypertrophy (though ok in hypertrophic cardiomyopathy)

• Bradycardia

• Hypokalemia

• Hypomagnesemia

• QT-prolonging states or drugs

Amiodarone (class III) adverse effects

Pulmonary Fibrosis

Hypo- or Hyper-thyroidism

Hepatitis

Skin photosensitivity/blue-gray skin discoloration

corneal deposits

optic neuropathy

QT prolongation (usually minimal increased risk for Torsades de Pointes)

Dronedarone (class III) adverse effects

TdP

bradycardia

N/V/D