7 Antiarrhythmia drugs Flashcards by Caitlin Pook

Describe the Vaughan Williams classification of antiarrhythmic drugs

I= Na channel blockers
- IA=moderate potency
- IB= least potent
- IC= most potent
II= Beta adrenergic blockers
III= K channel blockers
IV= Ca channel blockers

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What are the direct effects of class IA drugs? What are the indirect effects?

Direct: Primarily block Na channels:
- Increase AP threshold
- Decrease Vmax
- Increase ERP= increase AP duration
Indirect:
- blocks K channels -> EADs
- vagolytic effect (“brakes” on the PNS -> faster signal from atria to ventricles/through AV node)

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What are 3 main class IA drugs?

Na channel blockers:

quinidine, procainamide, disopyramide

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What are some side effects of IA drugs?

severe GI effects (quinidine)
vagolytic effect on heart
proarrhythmic (prolongs QT)
metabolized in the liver (quinidine… ok for pts with renal failure)

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What are some drug interactions for class IA drugs?

inhibit CYP2D6 (decreased metabolism of narcotics)
reduced renal clearance of digitalis

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What are 2 class IB drugs?

Lidocaine and mexiletine

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What are the direct effects of class IB drugs?

increase AP threshold
block Na channels (decrease Vmax)
- at high HR **use dependent
- and in depolarized cells (high affinity for inactivated Na channel; can target diseased/ischemic cells well)
decreases AP duration/ERP

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What are some side effects of class IB drugs?

CNS toxicity (neurons rely on Na!); dizziness, drowsiness, seizures
GI toxicity; nausea, vomiting

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When are class IB drugs used?

V tach
digitalis induced arrhythmias

**safe for patients with long QT syndrome (shortens AP)

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What are some drug interactions for class IB drugs?

drugs that interfere with CYP3A4 (e.g. cimetidine)
drugs metabolized by CYP1A2 (Mexiletine potently inhibits 1A2)

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What are 2 class IC drugs?

Flecainide and propafenone

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What are the direct effects of class IC drugs?

increased AP threshold
- few/variable effects on AP duration/ERP
decreased Vmax (conduction velocity)

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What are some side effects of class IC drugs?

pro-arrhythmic (increased incidence of malignant arrhythmias and mortality)
negative inotropic effect (can worsen heart failure)
dizziness, nausea
bradycardia (propafenone inhibits Ca channel and beta receptors)

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When are class IC drugs used?

Only approved in life threatening situations when SVT/ventricular arrhythmias are resistant to other drugs (because of pro-arrhythmic side effects)

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What are some drug interactions for class IC drugs?

drugs that inhibit CYP2D6… e.g:
- bupropion (antidepressant)
- ritonavir (antiretroviral)
- terbinafine (antifungal)
- cimetidine (H2 antagonist)
- amiodarone (antiarrhythmic drug)

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What are 3 class II drugs?

Propranolol, esmolol, metoprolol

What are the direct effects of class II drugs?

**Beta blockers

bind beta adrenergic receptors on cardiac cell membranes to competitively inhibit epi/NE binding
antagonize effects of sympathetic stimulation (slow rate of diastolic/phase 4 depolarization)

When are class II drugs used?

all atrial arrhythmias
ventricular tachycardia and fibrillation

**B blockers are currently the most useful antiarrhythmic drugs available due to their safety (don’t prolong AP; safe in long QT syndrome) and wide clinical applications

What are some side effects of class II drugs?

negative inotropic effect
heart block
bradycardia
bronchospasm

What are 3 class III drugs?

Amiodarone, sotalol, and dofetilide

What are the direct effects of class III drugs?

main common property= K channel blockers
- prolongs repolarization
- most common target= IKr (hERG channel)… can result in aquired long QT syndrome
- reverse use-dependent (more effective at a slower heart rate)
ultimately increase ERP

What are the effects of amiodarone? What is it commonly used for?

Major action= K channel blocker (both IKr and IKs)
modest Na channel blocker
modest Ca channel blocker
modest beta-adrenoreceptor blocker

**effective against v tach/fib and to prevent recurrent atrial fib/flutter

What are some common side effects of amiodarone?

triggered arrhythmias (from EADs) **Rarely associated with Torsades!
hypothyroidism
pulmonary fibrosis
hepatotoxicity

What are some drug interactions with amiodarone?

Inhibits P450s, dectreasing clearance of:

warfarin
digoxin
quinidine
flecainide
sildenafil (PDE5 inh)
simvastatin

What are the effects of sotalol? What is it commonly used for?

* major action= K channel blocker (IKr) * secondary action= beta blocker \*\*effective against V tach/fib, SVTs, and atrial fibrillation

What are some common side effects of sotalol?

* most serious= triggered arrhythmias with **Torsades de pointes** * fatigue * bradycardia

What are some drug interactions with sotalol?

\*\*Use with caution in conjunction with other drugs that _prolong QT_ (e.g. **class IA antiarrthmics**, tricyclic antidepressants, and quinolong antibiotics)

What are the effects of dofetilide? What is it commonly used for?

* major action= K channel blocker (IKr) \*\*effective against _atrial fibrillation and flutter_ (not hepatotoxic like amiodarone and safe for patients with L ventricular dysfunction)

What are some common side effects of dofetilide?

* most serious= triggered arrhythmias (_torsades de pointes!)_.... requires careful monitoring * headache * dizziness * chest pain

What are some drug interactions with dofetilide?

* drugs that interfere with renal secretion (dofetilide is eliminated via the kidney) * drugs that inhibit CYP3A4 (e.g. cimetidine)

What are 2 class IV drugs?

Diltiazem (benzothiazepines) and Verapamil (phenylalkylamines) \*\*Dihydropyridines NOT used for arrhythmias (they mainly target the vasculature, used for angina)

What are the effects of class IV drugs? What are they commonly used for?

* Ca channel blockers \*\*act primarily on slow response cells (SA/AV node) which are dependent on Ca influx for AP depolarization * increase AP threshold * increase nodal cell refractory period * depress conduction velocity in the SA and AV nodes \*\*commonly used for **SVT** (_rarely_ for v tach!)

What are some common side effects of class IV drugs?

* _negative chronotropic_ effect (_decreases automaticity of SA node)_ * _negative inotropic_ effect (decreases Ca influx during plateau phase of ventricular AP) * _hypotension_ (decreased Ca inlfux into vascular smooth mucle) * nifedipine= peripheral edema * verapamil= constipation * verapamil and diltiazem= * interacts with digitalis -\> slowed AV conduction -\> heart block * increase plasma digitalis (competes for renal excretion)

What are some drug interactions with class IV drugs?

Diltiazem and verapamil are moderate inhibitors of _CYP3A4_, reducing clearance of quinidine, _digoxin_, simvastatin

Describe the effects of adenosine

* very rapidly activates K channels to slow depolarization at the AV node * blocks cAMP enhanced Ca channel activity * **indicated for SVT** (slows AV conduction and HR)

Describe the effects of digoxin

* aka digitalis glycoside * enhances vagal parasympathetic activity to slow conduction at the AV node * indicated for **A fib and SVT** to control ventricular response rate

Describe the effects of ranolazine

* blocks persistent Na channel current (reducing excitability) and IKr * prolongs QT interval * used for treatment of chronic angina

Describe the effects of ivabradine

* inhibits the pacemaker funny current If * prolongs diastolic depolarization and slows SA node firing -\> **reduces HR**

Summarize when you would use different antiarrhythmic drugs

* IA for all arrhythmias (SVT, premature ventricular contraction, V tach, some effect on A fib) * quinidine, procainamide, disopyramide * IB for premature ventricular contractions and V tach * lidocaine and mexiletine * IC for premature ventricular contractions and V tach (some effect on SVT) * flecainide, propagenone * II and III for all arrhythmias * propranolol, amiodarone, sotalol * IV for SVT (some effect on A fib) \*\*nodal effects, don't help ventricular arrhythmias * Digitalis for SVT and A fib * Adenosine for SVT