Antiarrhythmic Drugs

Under class I drugs, which subclasses block sodium channels from 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? FIX CARD

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 (drugs that start w A-M like Atenolol, Metoprolol, etc) 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

How are amiodarone and dronedarone different from other Class 3 antiarrhythmics?

they have multi-channel blocking properties (actions in classes I, II, III and IV)

Class III drugs toxicity

Due to significant effects on potassium channels, Class III agents can prolong the QT interval and lead to ventricular arrhythmias. Risk of Torsades de Pointes

Class IV drugs MOA

Non-dihydropyridine L-type Ca2+ channel blockers that decrease phase 4 spontaneous depolarization, delay conduction through AV node, and display some use-dependence

What class drugs display use dependence? (bind more tightly at faster heart rates) fix

• Class I FIX

• Class IV

What antiarrhythmics are contraindicated in people with CHF? Why?

Class IV non-dihydropyridine calcium channel blockers (Verapamil and Diltiazem) — cause edema!

Toxicity of Class IV drugs

• Bradycardia

• Hypotension

• Edema

• Contraindicated in congestive heart failure

Adenosine (ATP) MOA

Binds to A1 adenosine receptor → activates Gi protein → inhibition of adenylate cyclase → ↓ cAMP → deactivation of L-type Ca2+ channels and activation of K+ channels:

• Slows sinus rate

• Slows conduction down AV node

Adenosine (ATP) adverse effects

Sense of doom

Clinical use of adenosine (ATP)

Arrhythmias depending on AV node (i.e. AVNRT, orthodromic AVRT)

Ivabradine MOA

Blocks spontaneous pacemaker current (aka funny current) in the sinus node → slows HR

Ivabradine adverse effects

Bradycardia

HTN

Afib

visual changes (phosphenes — colors or flashes you see when your eyes are closed)

Contraindications of ivabradine

• Patients with liver failure (bc ivabradine is metabolized in liver)

• Patients with AV block (who might be prone to symptomatic bradycardia)

Atropine MOA

• Blocks action of acetylcholine at parasympathetic sites

  in smooth muscle

atropine adverse effects

at low doses and slow administration, there's paradoxical bradycardia

what is used to treat symptomatic sinus bradycardia?

atropine

Digoxin clinical use

Use for A-Fib in patients with CHF

Digoxin MOA

Inhibits Na+/K+-ATPases → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+ concentration → increased contractility, decreased heart rate

Digoxin adverse effects

GI upset

alteration in color vision

PVC

Bradycardia

atrial tachyarrhythmias with AV block

junctional tachycardia