Anti-Arrythmics Flashcards
Unlike other regions of the heart, where phase 0 is driven by Na+ channels, the SA node and AV node have slower action potentials driven by
Ca2+ channels
Antiarrhythmic drug actions generally fall into 4 classes. Class 1 action is
Na+ channel blocker
Pronlong the PD and dissociate from the channel w/ intermediate kinetics and exhibit moderate blockade
Class 1A
The prototype class 1A drug is
Procainamide
Shorten the APD in some tissues of the heart and dissociate from the channel w/ rapid kinetics
Class 1B
The prototype class 1B drug is
Lidocaine
Have minimal effects on the APD and dissociate from the channel w/ slow kinetics
Class 1C
The prototype class 1C drug is
Flecainide
Class 2 action is sympatholytic and the prototypes are
Propranolol and esmolol
Prolongs the APD by blocking phase 2 K+ current
Class 3
What are the prototype class 3 drugs?
Sotalol, ibutilide, and amiodarone
Class 4 action is blockade of the cardiac
Ca2+ current
The prototype class 4 drugs are?
Verapamil and diltiazem
The prototype is procainamide but others are quinidine and disopyramide
Class 1A
Causes a slow upstroke of AP and prolongs the action potential duration
Class 1A drugs
Class 1A drugs can be used for
Atrial fibrillation or stable V-tach
Reduces peripheral vascular resistance
Procainamide
Slowing of conduction and AP prolongation increases the risk of
Torsade de pointes, syncope, and arrhythmias
Can cause a syndrome resembling lupus in 1/3 of patients receiving long-term therapy
Procainamide
Can cause atropine-like adverse effects such as urinary retention and dry mouth, as well as worsening of preexisting glaucoma
Class 1A drugs
Eliminated by hepatic metabolism to a metabolite which has class 3 activity
-accumulation of this metabolite can cause torsade de pointes
Procainamide
Class 1A prolongs the
Refractory period
Blocks activated and inactivated Na+ channels w/ rapid kinetics
Lidocaine
SHORTEN AP duration and the refractory period
Class IB drugs
Increased inactivation and slow unwinding kinetics results in the selective depression of conduction in depolarized cells. This is called
State Dependent Block
Toxicity causes parethesia, tremor, nausea, lightheaded ness, and hearing disturbances
Class 1B toxicity
Has extensive first pass metabolism
-Only 3% of orally administered lidocaine appears in the plasma
Class 1B
Used for arrhythmias associated w/ MI and used for termination of V-tach/prevention of V-fib
Class 1B
Ineffective for supraventricular tachycardias, atrial fibrillation, and atrial flutter
Class 1B drugs
An orally active congener of lidocaine used in the treatment of ventricular arrhythmias
-Also used for chronic pain from diabetic neuropathy and nerve injury
Mexiletine
Bind readily to activated channels (phase 0) or inactivated channels (phase 2) but bind poorly to rested channels
Use-dependent or State-dependent Drugs
Block electrical activity when there is fast tachycardia or when there is a significant loss of the resting potential
Use-dependent or State-dependent drugs
Selectively targets channels in depolarized tissue
Lidocaine
Have slow unblocking kinetics
Class 1C drugs
Have little effect on the action potential duration except for in the AV node and bypass tracts
Class 1C drugs
Toxicity cause provocation or exacerbation of potentially lethal arrhythmias including the acceleration of ventricular rate in patients w/ atrial flutter
Class 1C
Used for supraventricular arrhythmias and pharmacologic conversion of AF
Class 1C drugs
Shown in a study to increase mortality in patients convalescing from MI
Flecainide and propafenone (Class 1C drugs)
Can cause heart failure in patients with heart abnormalities
Class 1C Drugs
Decrease pacemaker activity and slow conduction through the AV node to increase the effective refractory period
Beta-blockers
A non selective beta-blocking drug that prolongs the action potential and is usually categorized as a class 3 drug
Sotalol
Lowers cAMP which results in reduction of both Na+ and Ca2+ currents and the suppression of abnormal pacemakers
Beta-blockers like propranolol
Particularly sensitive to beta-blockers
AV node
Decreases phase 4 slope and decreases myocardial oxygen demand
Beta-blockers
A non-selective beta antagonist that also exhibits Na+ channel blocking in vitro
Propranolol
An IV cardioselective beta-blocker that is effective in controlling the ventricular response in atrial flutter or fibrillation
Esmolol
Control the ventricular rate in atrial fibrillation or flutter, suppress PVCs, and terminate and prevent recurrences of paroxysmal supraventricular tachycardias
Beta-blockers
Beta-blockers are contraindicated in patients with
WPW syndrome
A use-dependent drug that blocks the “funny” current in the SA node and reduces heart rate w/out affecting myocardial contractility
Ivabradine
Made up of the pneumonic ISBAD which comprises ibutilide, sotalol, bretylium, amiodarone, and dofetilide
Class III antiarrhythmics
Usually classified as a class III because it markedly prolongs AP duration as well as blocks sodium channels
Amiodarone
Prolongs the AP duration by blockade of IK+ channels or by enhancing inward current
Class III drugs
AP prolongation increases the effective refractory period and reduces the ability of the heart to respond to rapid
Tachycardias
AP prolongation by many class III drugs are reverse-dependent, such that the AP prolongation is least marked at fast rates and most marked at slow rates where it can contribute to the risk of torsade de pointes. One exception to this is
Amiodarone
Prolonging AP can sometimes precipitate
Arrhythmias
Are more likely to develop in conditions that prolong AP duration
Early After Depolarizations (EADs)
A non selective beta-blcoking drug that is more effective for many arrhythmias than other beta-blockers because of its IK+ blocking activities
Sotalol
Can cause dose-related incidence of excessive QT-interval prolongation w/
Sotalol
Used to treat life-threatening ventricular arrhythmias and maintenance of sinus rhythm in patients w/ A-fib
Sotalol
Used therapeutically for the conversion of atrial flutter and fibrillation to normal sinus rhythm
Ibutilide and Dofetilide
Effective in most types of arrhythmias and is considered the most efficacious of all antiarrhythmic drugs likely due to its ability to block Na+, Ca2+, and Beta activity
Amiodarone
Is not reverse-use dependent and prolongs the AP duration over a wide range of HRs and prolongs the QT interval on the ECG by blockade of IKr
Amiodarone
Causes pulmonary fibrosis, microcrystalline deposits in the cornea and skin, and thyroid dysfunction
Amiodarone
Structural analogue of amiodarone, lacking iodine
-lacks major side effects of amiodarone
Dronedarone
Blocks IKur, IAch, and Ito in atria and is a less potent blocker of IKr
Vernakalant
Anti-ischemic drug for chronic angina
-Lessens incidences of supraventricular arrhythmias including AF
Ranolazine
Ca2+ channel blockers that are not useful as antiarrhythmics
Nifedipine and other dihydropyridines
Block both activated and inactivated Ca2+ channels which decreases conduction velocity and increases refractory period
Ca2+ channel blockers verapamil and diltiazem
Both verapamil and diltiazem also cause
Peripheral vasodilation
Major use is to prevent reentrant atrioventricular nodal re-entrant tachycardia (AVNRT) PSVT
-Contraindicated in WPW Syndrome
Diltiazem and Verapamil
Ca2+ channel blockers reduce automaticity by decreasing the
Phase 4 slope
Activated inward rectifier K+ current, inhibits Ca2+ and If current, and causes hyperpolarization and suppression of Ca2+-dependent APs
Adenosine
Drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%)
Adenosine
Cofactor for Na+/K+ ATPase and antagonist of Ca2+ channels
-Deficit is known to contribute to several arrhythmias
Magnesium
Used as an adjunctive agent and can help control ventricular response in A-fib and flutter and may terminate some paroxysmal (reentrant) supraventricular arrhythmias
Digoxin
