AntiArrhythmic Drugs

Question 1

Vaughan Williams Classification

Answer 1

Slow Automaticity (beta and calcium channel blockers esp AV node)

Change refractoriness and conduction velocity (potassium and sodium blockers)

Class I: Sodium Channel Blockers

Inhibit depolarization slowing conduction velocity

Class II: Beta-Blockers

Slow sinus and AV node

Class III: Potassium Channel Blockers

Prolong replorization and increased refractory period

Class IV: Calcium Channel Blockers (non-dihydropyridines)

Slow Sinus node (some) and AV node (more)

Others: Digoxin, adenosine, atropine

Question 2

Class I

Sodium Channel Blockers

Answer 2

IA (Prolong repolarization)

Agents: quinidine, procainamide, disopyramide

Uses: SVT, AF, VT but not used to much in lieu of better drugs

Side Effects: increase action potential watch QT, caution in renal dysfunctioj

IB (shortens repolarizaton)

Agents: lidocaine (IV), mexiletine (oral), phenytoin (rarely used)

Uses: ventricular tachcardias (esp with ischemia). Affinity for open Na Channels [thus better effect at faster heart rate (Na channels more likely to be open); little affect on atrial tissue because shorter action potential duration but large effect on diseased/ischemic and ventricular tissue]. Reduces action potential duraction so can be used for torsades de pointes or digoxin induced VT. lidocaine also used as local anesthetic

Side Effects: CNS symtoms, caution in hepatic dysfunction

IC (Prolong replorization)

Agents: Propafenone, Flecainide

Uses: (superventricular) _AF and refractory SVT _in structuarally normal hearts, slower kinetics, affinity to activated sodium channel. Most potent, watch for widening QRS

Side Effects: paresthesias, diplopia, chest pain, pro-arrhythmic!!! esp. in those with structural heart disease (e.g. post MI)

Question 3

Class II

Beta Blockers

Answer 3

Agensts:

First Generation Nonselective Beta agonist

** Propranolol,** timolol (short acting), pindolol (partial agonist)

Second Generation (Beta-1 selective agonist)

**Metoprolol, **atenolol (long acting), acebutalol (partial agonist)

Third Generation (produce vasodilation in addtion to cardiac ef)

Esmolol, carvediol (a1 block), celiprolol (partial B2 agonist), Nebivolo (release of NO by endothelial cells)

Uses: SVTs, VT, PVCs (atria and ventricules and those caused by excessive cathcholamine stress

Side Effects: bradycardia,fatigue, dizziness,hypotension, bronchospasm (propanolol), vasospams, rebound angina/tachycardia, CHF (acutely), fatigue, dizziness

Question 4

Class III

Potassium Channel Blockers

Answer 4

Agents: amiodarone,dronedarone, sotalol (also beta antagonist), dofetilide, ibutilide (IV)

Mechanism: blocks cardiac potassium channels which prolong refractoriness, (amiodarone also decreases conduction velocity phase 0 and automaticity phase 4)

Uses: AF (atrial fibrillation), Atrial flutter, (amiodarone and sotalol also treat VT)

Side Effects: long QT with risk of Torsades, sotalol reverse use dependence (greater drug effect at slower heart rate so may be better at preventing arrhythias than stopping them). Sotalol, dofetilide renally excreted contraindicated with renal dysfunction. Amiodarone has adverse effects in almost every organ system (thyroid, lung, liver function )

Question 5

Class IV

Calcium Channel Blockers (non-dihyrdopyridines)

Answer 5

Agents: verapamil, diltiaem

Mechanism: (most potent in tissues that depend where action potential depends on Ca AV and SA nodes) block L-type channels thus prolong AV node conduction & refractoriness, sinus node slowing (mild), reduce automaticity (mild), use-dependent properties

Uses: rate control for Atrial fib/atral flutter, SVT

Side Effects: bradycardia, CHF, fatigue, dizziness, constipation (verapamil), edema (diltiazem), hypotension, gingival hyeperplasia

Question 6

Digoxin

“from the Foxglove plant Digitalis Purpurea”

Answer 6

Class: Cardiac Glycoside (also called digitalis after plant name)

Mechanism: (1) increases contractility of failing heart (2) prolong refractory period of AV node in patients with SVT decreasing rate of transmission of atrial impulses to ventricles in SVT. Inhibits the Na/K ATPase which increases intracellular Na and this decreasese the outward flux of Ca via Na/Ca exchanger. Thus more Ca is pumped into sarcoplasmic reticulum so when cell receives action potential a greater than normal amount of Ca is released to myofilaments. In addition ionotrpic effect (CHF treatment), increases vagal tone and affect AV node

Uses: CHF (ionotropic effects), AF (atrial fibrillation) esp with CHF

Side Effects:narrow therapeutic range, bradycardia, AV block, or SVTand VT (delayed after depolarizations by increasing automaticity and decreasing refractoriness period) nausea, vomitting, visual disturbances/color changes,

Question 7

Adenosine

Answer 7

Class: endogenous nucleoside administered IV

Mechanism: (esp specialized conducting tissue) binds to adenosine A1 receptors activates potassium channels and decreases intracellular calcium, hyperpolarizes cell suppressing spontaneous depolarization of SA and AV node.

Uses: reentrant SVT

Side Effects: AV block, flushing, headache, chest pain, bronchospasnm (contradicted in ashmatics), AF via shortening of atrial refractoriness

Question 8

Atropine

Answer 8

Class: anticholinergic (muscarinic antagonist)

Uses: sinus bradycardia or AV block