Pharmacy Quiz: Anti-Arrhythmic Drugs

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Questions and Answers

What is the definition of arrhythmia?

Loss or abnormality of rhythm; denoting especially an irregularity of the heartbeat

What are the phases that the cardiac action potential is divided into?

4 phases

6 phases

5 phases (correct)

3 phases

Reentry is a concept that involves indefinite propagation of the impulse and continued activation of previously refractory tissue.

True

In the depolarization phase, rapid sodium channels in the cell membrane are stimulated to open, allowing positively charged ___________ ions to rush into the cell.

sodium Signup and view all the answers

Match the following phases of the action potential with their descriptions:

Phase 0 = Rapid influx of sodium ions into the cell Phase 1 = Initial rapid repolarization Phase 2 = Plateau phase sustained by calcium ion movement Phase 3 = Repolarization due to potassium channels Signup and view all the answers

What are the two major actions of Class II - β–adrenergic blockers?

Blockade of myocardial β–adrenergic receptors and direct membrane-stabilizing effects related to Na+ channel blockade Signup and view all the answers

Which type of arrhythmias are β-blockers most useful in treating?

Tachycardia Signup and view all the answers

All Class III antiarrhythmic drugs have the potential to induce arrhythmias. Is this statement true or false?

True Signup and view all the answers

What is the prototype medication for Class III K+ channel blockers that is now discontinued? It is __________.

bretylium Signup and view all the answers

Match the following antiarrhythmic drugs with their descriptions:

Amiodarone = Blocks multiple ion channels including sodium, calcium, and potassium; related structurally to thyroxine Dronedarone = An analog of amiodarone that is non-iodinated; has class I, II, III, and IV actions Sotalol = Has both β-adrenergic receptor-blocking and action potential-prolonging actions; formulated as a racemic mixture Dofetilide = Pure potassium channel blocker; used in atrial fibrillation and heart failure Ibutilide = Potassium channel blocker that also activates the inward sodium current; undergoes extensive first-pass metabolism Signup and view all the answers

What electrophysiologic property causes the pathway with the shorter refractory period to conduct electrical impulses more slowly?

slow conduction Signup and view all the answers

Which major pharmacologic mechanism does not belong to the group of antiarrhythmic drugs?

Miscellaneous group Signup and view all the answers

Class 1 antiarrhythmics primarily act by prolonging the action potential duration.

True Signup and view all the answers

Sodium channel blockers, such as lidocaine, shorten phase 3 repolarization and decrease the duration of the action potential by blocking activated and inactivated __________ channels.

sodium Signup and view all the answers

Match the Class I antiarrhythmics with their respective subclasses:

Procainamide = Class 1A Lidocaine = Class 1B Propafenone = Class 1C Signup and view all the answers

Study Notes

Normal Cardiac Function

Normal sinus rhythm (NSR) depends on:
- Generation of an impulse in the sinoatrial (SA) node pacemaker
- Conduction of impulse through:
  - Atrial muscle
  - Atrioventricular (AV) node
  - Purkinje conduction system
  - Ventricular muscle
Normal pacemaking and conduction require normal action potentials, dependent on sodium, calcium, and potassium channel activity, under appropriate autonomic control

Cardiac Action Potential

Describes electrical activity of an individual cardiac cell
The electrical impulse of the heart is the summation of thousands of tiny electrical currents generated by thousands of individual cardiac cells
Divided into five phases: 0-4

Depolarization (Phase 0)

Occurs when rapid sodium channels in the cell membrane are stimulated to open
Allows positively charged sodium ions to rush into the cell, causing a voltage spike

Repolarization (Phases 1-3)

Process of getting ions back to where they started
Corresponds to phases 1-3
Accounts for almost the entire duration of the action potential
The cell is refractory to depolarization until after it is repolarized

Resting Phase (Phase 4)

Period of time between two action potentials
Quiescent: no net movement of ions across the cell membrane

Abnormal Conduction

Mechanisms of tachyarrhythmias divided into two categories:
- Abnormality in impulse generation (automatic tachyarrhythmia)
- Abnormality in impulse conduction (reentrant tachyarrhythmia)

Disorders of Impulse Formation

Abnormal automaticity can occur in:
- Atria: automatic atrial tachycardia
- AV junction: automatic junctional tachycardia
- Ventricles: ventricular tachycardia

Reentry

Mechanism of abnormal impulse conduction
Requires:
1. Two roughly parallel conducting pathways connected proximally and distally by conducting tissue
2. One pathway has a longer refractory period than the other
3. The pathway with the shorter refractory period conducts electrical impulses more slowly than the opposite pathway

Antiarrhythmic Drugs

Classified into four main categories:
1. Sodium channel blockade (Class I)
2. Beta-adrenergic receptor blockade (Class II)
3. Prolongation of the action potential duration (Class III)
4. Calcium channel blockade (Class IV)

Sodium Channel Blockers (Class I)

Slow the upstroke of sodium-dependent action potentials and prolong QRS duration
Subclasses:
- Class Ia: procainamide, disopyramide, and quinidine
- Class Ib: lidocaine and Mexiletine
- Class Ic: propafenone and flecainide### Antiarrhythmic Agents
Idiosyncratic or immunologic reactions, including thrombocytopenia, hepatitis, and fever, are observed rarely.

Disopyramide

Effects are similar to procainamide and quinidine.
Cardiac antimuscarinic effects are more pronounced than quinidine, which may precipitate heart failure.
Should be administered with a drug that slows AV conduction when treating atrial flutter or fibrillation.

Disopyramide Side Effects

Toxic concentrations can precipitate electrophysiologic disturbances.
Negative inotropic effect may precipitate heart failure.
Atropine-like activity causes urinary retention, dry mouth, blurred vision, constipation, and worsening of glaucoma.

Lidocaine

Low incidence of toxicity and high degree of effectiveness in arrhythmias associated with acute myocardial infarction.
Class IB agents rapidly associate and dissociate from sodium channels.
Actions are manifested when the cardiac cell is depolarized or firing rapidly.
Blocks activated and inactivated sodium channels with rapid kinetics.
Shortens phase 3 repolarization and decreases the duration of the action potential.

Lidocaine Side Effects

Proarrhythmic effects, including SA node arrest, worsening of impaired conduction, and ventricular arrhythmias.
No negative inotropic effect.
Large doses, especially in patients with preexisting heart failure, may cause hypotension.
Paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions.

Mexiletine

Congener of lidocaine, orally active.
Electrophysiologic and antiarrhythmic actions are similar to those of lidocaine.
Side effects include tremor, blurred vision, and lethargy, as well as nausea.

Flecainide

Potent blocker of sodium and potassium channels with slow unblocking kinetics.
Slowly dissociates from resting sodium channels and shows prominent effects even at normal heart rates.
Very effective in suppressing premature ventricular contractions.
May cause severe exacerbation of arrhythmia even when normal doses are administered.
Side effects include blurred vision, dizziness, and nausea.

Propafenone

Has some structural similarities to propranolol and possesses weak β-blocking activity.
Sodium channel-blocking kinetics are similar to those of flecainide.
Similar side effect profile to flecainide.
May cause bronchospasm due to β-blocking effects.

β-Adrenergic Blockers (Class II)

Diminish phase 4 depolarization, depressing automaticity.
Prolong AV conduction.
Decrease heart rate and contractility.
Useful in treating tachyarrhythmias caused by increased sympathetic activity.

Class II β-Adrenergic Blockers

Based on two major actions:
- Blockade of myocardial β-adrenergic receptors.
- Direct membrane-stabilizing effects related to Na+ channel blockade.
The AV node is more sensitive than the SA node to the effects of β1-antagonists.

K+ Channel Blockers (Class III)

Class III agents block potassium channels, diminishing the outward potassium current during repolarization of cardiac cells.
Prolong the duration of the action potential without altering phase 0 of depolarization or the resting membrane potential.
Prolong the effective refractory period, increasing refractoriness.
All class III drugs have the potential to induce arrhythmias.

Amiodarone

Contains iodine and is related structurally to thyroxine.
Blocks sodium, calcium, and potassium channels and β adrenoceptors.
Has a broad spectrum of actions, which may account for its relatively high efficacy and low incidence of torsade’s de pointes.
Has a prolonged half-life of several weeks and is extensively distributed in adipose tissue.
May cause peripheral vasodilation.
Side effects include pulmonary fibrosis, neuropathy, and hepatotoxicity, as well as microcrystalline deposits in the cornea and skin.

Dronedarone

Benzofuran amiodarone derivative, which is less lipophilic and has lower tissue accumulation and a shorter serum half-life.
Does not have the iodine moieties responsible for thyroid dysfunction associated with amiodarone.
Like amiodarone, it has class I, II, III, and IV actions.
Liver toxicity has been reported.
A substrate and inhibitor of CYP3A4 and should not be co-administered with potent inhibitors of this enzyme.

Sotalol

Has both β-adrenergic receptor-blocking (class 2) and action potential-prolonging (class 3) actions.
Formulated as a racemic mixture of D- and L-sotalol.
All β-adrenergic-blocking activity resides in the L-isomer; the D- and L-isomers share action potential-prolonging effects.

Dofetilide

Pure potassium channel blocker.
Can be used as a first-line antiarrhythmic agent in patients with persistent atrial fibrillation and heart failure or in those with coronary artery disease.
Can cause torsades de pointes.

Ibutilide

Potassium channel blocker that also activates the inward sodium current (mixed class III and IA action).
Undergoes extensive first-pass metabolism and is not used orally.
Most important adverse effect is excessive QT-interval prolongation and torsade’s de pointes.

Calcium Channel Blockers (Class IV)

Class IV drugs are the nondihydropyridine calcium channel blockers verapamil and diltiazem.

Verapamil

Blocks both activated and inactivated L-type calcium channels.
Its effect is more marked in tissues that fire frequently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current.
AV nodal conduction time and effective refractory period are consistently prolonged by therapeutic concentrations.

Digoxin and Other Antiarrhythmic Drugs

Digoxin.
Adenosine.
Ivabradine.
Ranolazine.
Magnesium.
Potassium.

Adenosine

Naturally occurring nucleoside: a normal component of the body.
At high doses, decreases conduction velocity, prolongs the refractory period, and decreases automaticity in the AV node.
Cardiac mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current.

Ivabradine

Selective blocker of If (funny channel: pacemaker current).
Ivabradine slows pacemaker activity by decreasing diastolic depolarization of sinus node cells.
It is an open channel blocker that shows use-dependent block.

Ranolazine

Was originally developed as an antianginal agent.
Has antiarrhythmic properties that are dependent on the blockade of multiple ion channels.
Blocks the inward sodium current in the heart.
Also blocks the rapid component of the delayed rectifier K+ current IKr.

Magnesium

Originally used for patients with digitalis-induced arrhythmias who were hypomagnesemic.
Magnesium infusion has been found to have antiarrhythmic effects in some patients with normal serum magnesium levels.
The mechanisms of these effects are not known, but magnesium is recognized to influence Na+/K+-ATPase, sodium channels, certain potassium channels, and calcium channels.

Potassium

Hypokalemia results in an increased risk of early and delayed afterdepolarizations, and ectopic pacemaker activity, especially in the presence of digitalis.
Hyperkalemia depresses ectopic pacemakers (severe hyperkalemia is required to suppress the SA node) and slows conduction.

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Description

This quiz covers anti-arrhythmic drugs and normal electrical cardiac function, including the sinoatrial node pacemaker and conduction pathways.