Antiarrhythmics Flashcards
Describe the SA/AV node action potential
-phase 0= depolarization, Ca2+ influx/entry
-phase 3= repolarization, K+ efflux
-phase 4= pacemaker potential/spontaneous gradual depolarization, opening of special Na+ channels, inward Na+ entry (If-funny, slow Na+ channel)
What characteristics of phase 4 of AV/SA node indicates automaticity?
positive slope
What are the proposed mechanisms of tachyarrhythmias?
-enhanced/abnormal automaticity of SA node (further increase in phase 4 slope)
-conduction re-entry at AV, “dog chasing it’s tail”
-enhanced automaticity due to diastolic “leaky” channel of myocytes/purkinje cells (increased phase 4 slope)
Describe Phase 0 of Myocyte and Purkinje action potential
depolarization, use fast voltage gated Na+ channels
Explain propagation of action potential along cardiac cells through gap junctions
gap junctions are important for intercellular communication (Na+ movement) and spread of depolarization from one cell to another by fast voltage gated Na+ channels allowing rapid depolarization
What are the 3 stages of voltage gated Na+ channels?
-resting
-activated
-inactivated
What is the difference between myocyte and purkinje ion movement?
only purkinje have phase 1, transient K+ channels open and K+ efflux returns
What are the results of increase phase 4 slope?
- mechanical stretch of cardiac muscle cells
- hypokalemia/hypocalcemia
- beta stimulation
- hypoxia/ischemia
What is the mechanism for hypokalemia/hypocalcemia when there is increased phase 4 slope?
decreased outward leak of K+
What are the causes of Delayed after-depolarizations (DAD) aka intracellular Ca2+ overload?
myocardial ischemia, adrenergic stress, and Digoxin (digitalis toxicity)
What are the causes of Early after-depolarization (EAD) aka inward movement of Na+ or Ca2+ during phase 3?
phase 3 prolongation due to slowed repolarization, long QT interval, slow rate
What are the therapeutic treatment options for Delayed after-depolarization (DAD)?
-Ca2+ channel blockers
-Na+ channel blockers
-beta blockers
What are the therapeutic treatment options for Early after-depolarization (EAD)?
-Ca2+ channel blockers
-beta blockers
What drugs can treat conduction re-entry arrhythmias?
-Na+ blockers
-K+ channel blockers
-amiodarone
Describe Class 1 Na+ channel blockers
use/state/frequency- dependent fast Na+ channel blockers, channels that are used more frequently (activated) or are more inactivated state are more susceptible to block
What is the goal physiology of using Type 1 Na+ channel blockers?
stabilize membrane, depress 0 phase
What is the MOA of Class 1A Na+ channel blockers?
block fast Na+ channels (OPEN, ACTIVE Na+ CHANNELS) with moderate potency to decrease phase 0 upstroke velocity (decrease conduction velocity) and prolongs effective refractory period (ERP)
What is the MOA of the adverse effect of QT prolongation and Torsades de pointes in Class 1A Na+ channel blockers?
may also block K+ channels= reducing the K+ current which is responsible for repolarization of the membrane which can increases the effective refractory period
-> increased action potential duration= QT prolongation
-> QT prolongation= torsades de pointes
What effects do Type 1A Na+ channel blockers have on automaticity?
-little effect on SA node
-suppress automaticity of purkinje fibers by reducing the slope of phase 4 depolarization
What are the uses of Type 1A Na+ channel blockers?
NOT FIRST LINE, but due to MOA could treat DAD and conduction re-entry arrhythmias
What is the use of Quinidine?
Class 1A Na+ channel blocker, 2nd or 3rd line agent!
used for re-entry arrhythmias, paroxysmal supraventricular tachycardia (PSVT) and ventricular tachycardia (VTs)- slows conduction and prolongs the effective refractory period, and Afib
What is a unique MOA of Quinidine in class 1A antiarrhythmics?
anticholinergic (vagolytic) effects
What are the adverse effects of Quinidine?
-slows cardiac conduction= prolonged QRS duration, or SA/AV node disturbances
-Proarrhythmic effects= torsades de pointes due to prolonged QT interval
-CNS toxicity= cinchonism (tinnitus, hearing loss), confusion, vision disturbances, delirium, psychosis
What drug class does Procainamide belong to?
Class 1A Na+ channel blockers
What are the effects of Procainamides metabolites?
procainamide -> N actyl procainamide (NAPA)
has different effects than parent compound, K+ channel blocker (class 3 activity) and prolongs action potential duration (APD) of ventricular and purkinje fibers which is responsible for the SE of QT prolongation and torsade de pointes
What are the adverse effects of Procainamide?
-chronic therapy= systemic lupus like syndrome
-NAPA (metabolite) may cause QT prolongation and torsades de pointes
What is the MOA of Class 1B Na+ channel blockers?
block Na+ channels in OPEN and INACTIVATED conformation (rapid binding/unbinding) preferable targeting abnormal tissue (depolarized, arrhythmogenic tissue= no effect on healthy tissue) making ischemic cardiac myocytes the preferred target due to more open and inactive Na+ channels
slightly decreases APD
Class 1B Na+ channel blockers have no effect on QT interval- WHY?
no K+ channel block
What drug class is Lidocaine?
Class 1B Na+ channel blocker
What is the use of Lidocaine?
ventricular arrhythmias (VT or VF) in emergent situations, high degree of effectiveness seen with acute MI
not suitable for supraventricular arrhythmias
What are the adverse effects of Lidocaine?
-negative inotropic effect
-bradycardia, SA node depression, and His-purkinje block
What drug class is Mexiletine?
Class 1B Na+ channel blocker
What are the uses of Mexiletine?
-oral treatment for symptomatic ventricular tachyarrhythmias (VT)
-prophylaxis of ventricular arrhythmias
-long QT syndrome
-children with congenital heart disease and ventricular arrhythmias
What are the adverse effects of Mexiletine?
severe bradycardia and abnormal SAQ node recovery in patients with sinus node disease
- N/V, tremor, dizziness, and confusion (dose related)
What is the MOA of Class 1C Na+ channel blockers?
potent Na+ channel blockers (OPEN CHANNELS, slow binding/unbinding) and decreases rate of phase 0 upstroke on ventricular, atrial, and purkinje cells with little to no effect on APD
What drug class is Flecainide?
Class 1C Na+ channel blocker
What are the side effects of Flecainide?
-proarrhythmic (convert AFib -> atrial flutter)
-negative inotropic effects (worsen HF episodes)
-increased mortality or non fatal cardiac arrest
What drug class is Propafenone?
Class 1C Na+ channel blocker
What are the adverse effects of Propafenone?
weak beta antagonist= prolongs QRS
-proarrhythmic (less common than Flecainide)
-cardiovascular effects= AV block, sinus depression, worsening HF
-metallic taste
What is the MOA of Class 2 beta blockers?
affects primarily SA and AV node through beta receptor blockade which decreases rate of spontaneous phase 4 depolarization= decrease automaticity, prolongs repolarization= increases effective refractory period= decreases incidence of re-entry, decrease automaticity of SA and AV conduction, and blocks sympathetic effects on the heart
What are the uses of Class 2 beta blockers?
ventricular and supraventricular tachyarrhythmias precipitated by sympathetic stimulation
What are the adverse effects of Class 2 beta blockers?
-cardiovascular events= excessive neg inotropic effects, heart block, bradycardia, AV block, hypotension
-impotence
-CNS= insomnia and depression
-smooth muscle spasms= bronchospasms (caution in asthma or COPD)
What drug class is Propranolol?
class 2 beta blocker
What is the 1/2 life of Propranolol?
2-6h
What are the uses of Propranolol?
-prophylaxis of paroxysmal supraventricular tachycardia (PSVT)
- ventricular tachycardia (VT)
-management of pheochromocytoma (catecholamine producing tumor)
-short term treatment of tachycardia and arrhythmias due to thyrotoxicosis (hyperthyroidism)
Which generation of beta blocker is most cardioselective?
2nd gen
What drug is a 2nd gen beta blocker?
metoprolol
What is the use of Esmolol?
emergency situations due to short 1/2 life (biphasic= 3-4 minutes, 15 minutes)
What is the MOA of Class 3 antiarrhythmics?
-inhibit repolarization by inhibiting K+ channels involved in repolarization= increase absolute refractory period
-significantly prolong action potential duration (APD)
-little effect on phase 0 depolarization
What is the MOA of Sotalol?
has beta adrenergic blocking activity as well as K+ block which prolongs action potential duration (APD), increased refractory period of atria and ventricles, and inhibits conduction in accessory pathways
What are the indicated uses of Sotalol?
-treatment of life threatening ventricular arrhythmias
-maintenance of sinus rhythm in pt with AFib
What are the adverse effects of Sotalol?
-QT PROLONGATION -> torsades de pointes
-beta blocker SE
What are the monitoring parameters for Sotalol?
ECG for 72h
What is the MOA off Amiodarone?
-blocks K+ channels= prolongs APD
-blocks inactive Na+ channels
-blocks beta adrenergic receptors(weakly)
-blocks Ca2+ channels(weakly)
What are the uses of Amiodarone?
-wide range of uses in atrial and ventricular arrhythmias (drug with MOST EFFICACY)
-ventricular tachyarrhythmias
-supraventricular arrhythmias
-AFib
What is the 1/2 life of Amiodarone?
50-60 days
What are the adverse effects of Amiodarone?
-cardiovascular: decreased AV or SA node function (bradycardia, heart block), decreased cardiac contractility, hypotension
-highest incidence of torsades de pointes
-pneumonitis leading to pulmonary fibrosis
-hyper OR hypo-thyroidism
-elevated liver enzymes
-peripheral neuropathy, headache, ataxia, tremors
-corneal microdeposits (100% of pt will experience this after 6 months therapy)
-testicular dysfunction
-skin discoloration
Describe how Amiodarone can cause hypothyroidism
inhibits T4 to T3 conversion (2-4% of population)
Describe how Amiodarone can cause hyperthyroidism
excess iodine induces thyroid hormone synthesis
What is the MOA of Dronedarone?
primarily K+ channel blocker but also very similar to Amiodarone
How does Dronedarone compare to Amiodarone?
-less potent
-shorter t1/2 life (24h)
-less SE, but cardiovascular, elevated liver enzymes, and neurological SE still remain (to lesser extent)
What is the MOA of Dofetilide?
K+ channel block= prolonged action potential (APD)
What is the indication of Dofetilide?
AFib
What are the adverse effects of Dofetilide?
QT interval prolongation= torsades de pointes
monitor ECG for 72h
What are the indications of Ibutilide furamate?
AFib
What are the adverse effects of Ibutilide furamate?
Qt prolongation= torsade de pointes
monitor ECG for 8h, short 1/2 life (IV prep)
What classes of antiarrhythmic drugs prolong the QT interval?
class 1A and 3
What are the class 4 antiarrhythmics?
calcium channel blockers (non-DHPs)
What is the MOA of Class 4 Calcium Channel Blockers (Non-DHP)?
-blocks both active and inactive L-type Ca2+ channels
-slows action potential of SA and AV node= slows diastolic depolarization
-depresses automaticity of SA and conduction of AV
-prolongs refractory period at AV node
What are the uses of Class 4 calcium channel blockers?
-rate control in AFib
-paroxysmal supraventricular tachycardia (PSVT)
-EAD and DAD
What are the adverse effects of Class 4 calcium channel blockers?
-arrhythmias
-AV block
-bradyarrhythmia
-HF exacerbation
-gingival hyperplasia
-hypotension
-peripheral edema
-syncope
