Anti-Arrhythmics Flashcards
When & why do early afterdepolarizations occur? What about delayed afterdepolarizations? What are three common conduction block abnormalities? What is the major determinant of conduction velocity? What three requisite conditions exist for re-entrant arrhythmias? Favored by?
Abnormal Automaticity: EADs – during phase 3, decreased K+ current (or increase late sodium, late calcium current). DADs – during phase 4, decreased K1 current (or increased diastolic Na, Ca influx – decreased NCX – this is the mxn for cardiac glycoside induced arrhythmias). Common conduction block abnormalities: SAN, AVN (I, II, III), BBB. Major determinant of conduction velocity: cardiac sodium current – 1. rate of phase 0 depolarization, 2. threshold potential, 3. resting potential. For re-entry: Unidirectional block (asymmetric excitability), slow conduction (decremental conduction), conduction time > refractory period. Favored by: tissue heterogeneity (refractory period, gap junction coupling, fibrosis), extrasystoles.
What are the two mos common supraventricular tachycardias?
1 - AV node re-entry (dual AVN conduction pathways). 2 - Bypass tract re-entry (AVN & bypass tract re-entry).
Treat sinus tachycardia how? What about paroxysmal SVTs? What slows but not terminates junctional tachycardia? What is junctional tachycardia commonly caused by? What about re-entrant SVTs?
Vagal stimulation (carotid massage), ACh, BB, AVN blocking agents (verapamil, adenosine), catheter ablation + pacemaker. SVTs: vagal stimulation, BB, AVN blockers. Junctional tachycardia is slowed but not terminated by vagal stimulation – commonly caused by cardiac glycoside toxicity. SInus node re-entry: electrical stimulus. Atrial re-entry: electrical stimulus (not responsive to vagal tone). AV node re-entry (remember that this is most common of all SVTs): vagal tone, adenosine, BBs, CCBs.
What happens in Wolff-Parkinson-White Syndrome? How is it treated?
Fast AV accessory pathway (bundle of Kent) with a shortened PR interval, wide QRS, delta wave. Tx: Not responsive to vagal tone, AVN blockers contraindicated. Treat with amiodarone, procainamide, cardioversion, ablation – MUST BLOCK the accessory pathway.
How are catecholamine induced ventricular tachycardias treated? How are the three types of long QT syndrome treated?
Tx: BB, ICD, sympathectomy. For LQT1: BB. LQT2: BB less effective, K+ therapy. LQT3: BB less effective, need to block late sodium current.
Is atrial flutter treated? When is this life-threatening? How is atrial fibrillation treated? What about ventricular flutter and ventricular fibrillation?
Not life-threatening unless transmitted to ventricles at a rapid rate (WPW). Vagal stimulation, CCBs not effective. Tx for a fib: anticoagulatns, rate control, anti-arrhythmics for rest of life (a fib increases the risk of stroke, HF, SCD) Ventricular flutter is lethal if not terminated – cardioversion, ICD required, antiarrhythmics may be pro-arrhythmic. The same goes for ventricular fibrillation.
What is the classification for anti-arrhythmic drugs?
I (drugs with direct membrane action – Na channel blockade): Ia – depress phase 0 (slow conduction, prolong repolarization), Ib – little efect on phase 0 in normal tissue (depress phase 0 in abnormal fibers, shorten repolarization), Ic – markedly depress phase 0 in fast-response fibers – cardiac muscle, His-Purkinje (markedly slow conduction, slight effect on repolarization). II: Sympatholytic (BB): slow phase 4 in pacemaker fibers. III: Prolong Phase III repolarization. IV: CCBs – slow/block phase 0 in slow-responsive fibers (SA, AV nodes), slow phase 4 in pacemeaker fibers.
What class is quinidine? MOA? Uses? What limits use?
IA: fast (open) Na channel block, prolongs effective refractory period, prolongs action potential duration. Use: alternative for atrial flutter, fibrillation SVT (NEVER for ventricles). Also: alpha-adrenergic blockade, M2 blockate, vagal inhibition, may increase AVN transmission. Use is limited by toxicities: diarrhea, nausea, fever, hep, thrombocytopenia, cinchonism, TdP + numerous drug interactions: hyperkalemia enhances effects, digoxin (plasma binding), CYP2D6 inhibition, induced by phenobarbital, phenytoin
What class is procainamide? MOA? Use? Toxicities?
IA: fast (open) Na channel block, prolongs effective refractory period, prolongs action potential duration. Use: alternative for atrial flutter, fibrillation SVT, v fib. Also: local anesthetic properties, but no alpha-adrenergic properties or M2 blockade. Toxicities: drug-induced lupus, TdP, active metabolite causes hypotension.
What are the IA drugs? Again, what do they do at high concentrations? What about at normal concentrations?
Quinidine, procainamide, disopyramide. Block inward potassium rectifying channel (slow rate) at normal concentrations; blocks sodium channels (fast rate) at high
concentrations.
What are the IB drugs? Which one is no longer available? Why? MOA: What are these used for? How is the main one given? Why? What’s the oral form of this?
Lidocaine, mexiletine, tocainide (not in U.S. - fatal bone marrow aplasia, pulm fibrosis). MOA: Na channel block (open, inactivated), with preference for depolarized (ischemic) tissue and inactivated Na channels Lidocaine: for dig tox, emergency VT/VF, cardioversion, alternative for acute suppression of VF, NOT for atrial. Also: Local anesthetic. Lidocaine is given IV because of 1st pass metabolism. Mexiletine is an oral form.
What are the IC drugs? MOA? Uses? Still, why aren’t these drugs used much and what are they contraindicated in?
Flecainide, propafenone, moricizine. MOA: Sodium channel block (strongest of all Class I drugs), esp His-Purkinje – very slow unbinding, greatly prolonging sodium current recovery, prolonging PR, QRS, QT interval w/o EADs or TdP. Use: Alternative for acute management of a fib, SVT, primary for maintenance of sinus rhythm in chronic AF, SVT in patients w/o structural heart disease. Toxicities: Worsened heart failure, pro-arrhythmia in ischemic tissue, increased mortality – contraindicated in heart failure, VT.
What are the II drugs mostly used? MOA? As anti-arrhythmics, these drugs are used for what? And, of course, these drugs decrease mortality in…? Contraindicated in? Don’t do this with these drugs? When is esmolol used?
Propanolol, Carvedilol, Metoprolol, Acebutolol, Esmolol. MOA: BBs, decrease SA, AV node activity (decrease phase 4 depolarization). Primary use is control of ventricular rate in a flutter/fib, prevent/terminate SVTs. Decrease mortality in CHF! Contraindicated in WPW, never sudden withdrawal of BB in angina –> can cause MI. Esmolol: IV with short half-life, useful in acute emergenchy tx of SVTs.
What are the III drugs? MOA? General use? Amiodarone is conraindicated when? What are some side effects?
Sotalol, amiodarone (most commonly used anti-arrhythmic drug), dofetilide, ibutelide, dronedarone. MOA: K+ channel blockade, slowing phase 3 repolarization of the AP, prolonging AP duration refractoriness, esp. in Purkinje & ventricles. Use: Amiodarone (half life > 80 days!) can be used for almost all arrhythmias: atrial fibrillation/flutter, paroxsymal supraventricular tachycardia, ventricular tachycardia, NOT digitalis toxicity or during pregnancy (thyroid affects). Side effects: Torsades de Pointes; QT prolongation, pulmonary fibrosis, peripheral neuropathy, hepatic dysfunction photosensitivity (blue-gray skin), numerous drug interactions.
What are IV drugs? MOA? Use? Contraindicated in? An important side effect is?
Nifedipine, amlodipine, felopidine, isradipine, veapamil, diltiazam. MOA: L-type Ca block –> slow SA, AV node, decrease phase 0 and phase 4 of APs. Use: Prevent or terminate reentrant SVTs, A fib/flutter. Contraindicated in WPW. Sde effect: Increase serum digoxin levels, AV block effects additive with digoxin, BBs.
Adenosine MOA? Use? Side effects?
MOA: adenosine receptors in atrium, sinus node, AV node –> activates K current, shortening AP, hyperpolarizing tissue, and slowing down automaticity and AV conduction. Use: adminisered IV b/c half life < 10 seconds – terminate PSVT, AVN re-entrant, not a fib/flutter, WPW. Side effects: sedation, dyspnea, hypotension, antagonized by methylxanthines, reflexive symp activation.
Cardiac glycosides (digoxin) MOA? Use? Use is limited because?
MOA: Na/K pump inhibitor; slows AVN activity and
conduction. Use: Atrial fibrillation/flutter; chronic SVT. Use is limited due to low therapeutic index: Nausea, cognitive dysfunction, blurred or yellow vision, lethal DAD arrhythmias – interactions with quinidine, flecainide, propafenone, amiodarone, verapamil, diltiazem (requires dose adjustment).
Magnesium is useful for?
Preventing recurrent TdP and some digitalis-induced arrhthymias. Alternative to amiodarone for shock refractory cardiac arrest.
1 & 2 tx for acute, chronic a fib/flutter?
1º IV verapamil, diltiazem, b-blocker, or digoxin, DC cardioversion (ibutilide may help)
precardiac surgery: b-blockers, sotalol, amiodarone
2º IV procainamide, ibutilide, dofetilide
single large oral dose propafenone or flecainide
Chronic Atrial Fibrillation or Flutter
1º rate control with verapamil, diltiazem, b-blocker, or digoxin; maintain sinus rhythm with amiodarone, sotalol, flecainide, propafenone, or dofetilide, radiofrequency (RF) ablation
2º quinidine, procainamide, disopyramide
1 & 2 tx for acute, chronic SVTs?
Acute SVTs
1º IV adenosine, verapamil, diltiazem
2º IV esmolol, b-blockers, digoxin for termination
Chronic SVTs
1º b-blockers, verapamil, diltiazem, flecainide, propafenone,
amiodarone, sotalol, or digoxin
DC cardioversion, atrial pacing effective but rarely required
2º quinidine, procainamide, disopyramide
RF ablation may cure most patients
1 and 2 tx for PVCs or nonsustained VT?
1º asymptomatic, no structural heart disease = no treatment; symptomatic: b-blockers
2º none
post-MI: only b-blockers proven to decrease mortality
IC antiarrhythmics worsen mortality
1 and 2 tx for sustained VT?
1º amiodarone, ICD (intracardiac device)
2º procainamide, lidocaine
1 and 2 tx for v fib?
1º amiodarone, ICD
2º procainamide, lidocaine
1 and 2 tx for cardiac glycoside-induced VT?
1º digoxin-immune Fab fragments (Digibind, Digifab)
2º sustained VT/VF: DC cardioversion,
b-blocker, procainamide may worsen heart block
1 and 2 tx for drug-induced TdP?
1º discontinue offending drug, magnesium sulfate, KCl
2º cardiac pacing, isoproterenol
What is the primary mechanism for prolonged QT interval arrythmias? What is this enhanced by? What will increasing K+ currents do?
EADs are the primary mechanism for prolonged QT interval arrhythmias. Enhanced by: 1 - increases in INa or ICa,L, 2 - slow heart rates. Increasing K+ currents will suppress EAD formation.
