Anti-Arrhythmic Drugs Flashcards
Quinidine
Class Ia
Mechanism: block rapid inward Na+-->Decrease Vmax of phase 0-->slow conduction block K+-->increase APD block alpha receptors-->decrease BP Block M receptors--> increase HR
Use: Refractory pts= convert symptomatic AF or flutter, prevent recurrence of AF, treat life-threatening ventricular arrhythmias
Adverse effects: nausea, vomiting, diarrhea, cinchonism, hypotension, proarrhythmic (torsades de pointes-increase QT interval)
Procainamide
Class Ia
Mechanism:
block rapid inward Na+ channel–>slows conduction, automaticity, excitability
block K+ channel–>prolong APD & refractoriness
Use: life threatening ventricular arrhythmias; supraventricular (acute)=reentrant SVT, A fib, atrial flutter associated with Wolff-Parkinson-White syndrome (WPW)
Adverse effects: arrhythmia aggravation, torsades de pointes (long QT), heart block , sinus node dysfunction, SLE-like syndrome, GI nausea/vomiting, decreased kidney function
Disopyramide
Class Ia
Mechanism:
block Na+–>moderate effect on phase 0 depolarization
block K+–>delayed phase 3 repolarization–>prolonged QRS and QT
Moderate block of M receptors–>increase HR
Lidocaine
Class Ib
Mechanism:
blocks open and inactivated Na+–>reduces Vmax–>shortens cardiac AP (in ischemic tissue)
Lowers slow of phase 4–>alters threshold
Use: ventricular arrhythmias post MI, second choice for life-threatening arrhythmias
Pharmacokinetics: first-pass hepatic metabolism–>IV use (need multiple loading doses)
Adverse Effects: bolus= tinnitus, seizure; high doses= drowsiness, confusion, hallucinations, coma; cardiac function decrease–>decrease clearance, increase concentration
Phenytoin
Mexiletime
Tocainide
Class Ib
Mechanism:
weak bind Na+–>weak effect on phase 0 depolarization
accelerates phase 3 repolarization–>shortened APD and QT
Use: digitalis and MI-induced arrhythmias
Propafenone
Class Ic
Mechanism:
strong inhibitor of Na+–>effect phase 0 depolarization
inhibit beta receptors–>decrease HR
Use: atrial arrhythmias, PSVT, ventricular arrhythmias (pts MUST have preserved ventricular function)
Flecainide
Class Ic
Mechanism:
potent Na+ block–>prolongs phase 0 and widens QRS–>slows intraventricular conduction
Use: refractory life-threatening ectopic ventricular arrhythmia
Adverse effects: propensity for fatal proarrhythmic effects
Moricizine
Class Ic
Mechanism:
strong Na+ block–>effect phase 0 depolarization–>lengthened QRS, ADP, and PR
Little effect on repolarization (QT unchanged)
Metoprolol Propranolol Esmolol Atenolol Timolol Carvdilol
Class II
Mechanism:
beta blockers–>decrease SA nodal automaticity (phase 4 lower slope), AV nodal conduction, ventricular contractility
Use: supraventricular arrhythmias due to excessive sympathetics, ONLY drugs clearly effective in preventing sudden cardiac death in pts with prior MI
Amiodarone
Class III
Mechanism:
block K+–>prolongs refractoriness and APD
blocks Na+ in inactivated state
block Ca2+–>slows SA node phase 4
slows conduction through AV node
Noncompetitive blockade of alpha, beta, and M receptors
Use: AF, AV nodal reentrant tachycardia, WPW tachycardia, life-threatening VT or VF, IV for acute termination of VT or VF for cardiac arrest
Pharmacokinetics: highly lipid-soluble (diffuses to other tissues), long half life
Adverse effects: high IV dose= decrease cardiac contractility–>hypotension; interstitial pneumonitis; hyper or hypothyroidism; corneal microdeposits; photosensitivity; elevated serum hepatic enzyme levels
Dronedarone
Sotalol
Ibutilide
dofetilide
Class III Mechanism: strong K+ block-->prolong phase 3 repolarization-->increase QT block Na+ block Ca2+ block Beta receptors
Use: ventricular re-entry/fibrillatory arrhythmia
Verapamil
Diltiazem
Class IV
Mechanism:
block slow inward Ca2+ channels in nodal tissue
decrease SA automaticity–>decrease HR
decrease AV conduction–>increase PR interval
decrease ventricular contractility and HR
ineffective on ventricular arrhythmia
Ratio of vasodilation to negative inotropy is 1:1
Use: supraventricular tachycardia, rate control in Afib, angina pectoris, hypertension
Adverse effects: headache, flushing, dizziness, ankle edema, constipation, exacerbate CHF, hypotension, AV block in combo with beta blocker
Contraindications: sick sinus syndrome, AV nodal disease, WPW syndrome with Afib, ventricular tachycardia
Adenosine
Mechanism:
activate A1 receptor in SA and AV nodes–>activate cAMP-indepedent, Ach/Ado-sensitive K+ channels=
SA node hyperpolarization and decrease firing rate
Shortening of AP duration of atrial cells
Depression of A-V conduction velocity
Activates A2 receptor in vasculature–> K+ channels
Increase endothelial Ca2+–>increase NO
Smooth muscle hyperpolarization–>vasodilation
Use: acute conversion of supraventricular tachycardia cause by reentry involving accessory bypass pathway
Pharmacokinetics: must use as IV bolus (half life= 10-15 sec)
Adverse effects: hypotension, flushing, complete heart block, CNS effects, dyspnea
Nitroglycerin (GTN)
Organic nitrate for MI
Mechanism:
prodrug undergos denitrification by mitochondrial aldehyde reductase
NO activate soluble GC–>increase cGMP–>cGK-1 activation–>increase mitochondrial Ca2+ uptake–> decrease Ca2+ influx–>phosphorylate MLCK–>vasorelaxation
potent vasodilation in veins–>decrease preload
Tolerance develops if constant dose
No effect on coronary resistance vessels
Pharmacokinetics: hepatic intravascular metabolism, sublingual or transdermal
Use: acute attacks of angina, prophylactic therapy before activity leading to angina, CHF, MI
Adverse effects: headache, hypotension, erythema, local edema, methemoglobinemia
Isosorbide dintrate (ISDN)
Organic nitrate for MI
Mechanism:
prodrug undergos denitrification by mitochondrial aldehyde reductase
NO activate soluble GC–>increase cGMP–>cGK-1 activation–>increase mitochondrial Ca2+ uptake–> decrease Ca2+ influx–>phosphorylate MLCK–>vasorelaxation
potent vasodilation in veins–>decrease preload
Tolerance develops if constant dose
No effect on coronary resistance vessels
Pharmacokinetics: rapidly metabolized; sublingual, phasic, sustained release form–>QD dosing (avoid tolerance)
Use: acute attacks of angina, prophylactic therapy before activity leading to angina, CHF (in combo w/ hydralazine good for African Americans), MI
Adverse effects: headache, hypotension, erythema, local edema, methemoglobinemia
