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Flashcards in Antiarrhythmic Deck (35):

1. Define cardiac arrhythmia and cardiac excitability.

Cardiac arrhythmia → loss of cardiac rhythm due to (1) disturbance in impulse formation, (2) disturbance in impulse conduction, (3) both
Cardiac excitability → ease with which cardiac cells undergo sequential depol and repol, communication with adjacent cells and propagation of electrical activity.


2. What is the fast and slow response cardiac action potentials?

Fast → atria, ventricles, purkinje fibers [tissues that depend on VG, rapid opening sodium channels to initiate depolarization]
Slow → SA and AV node


3. What are the different phases of “fast response” cardiac action potentials?

Phase 0 → rapid depolarization due to VG Na+ channels opening then inactivating. Calcium channels also open during depolarization but the influx of calcium is much slower.
Phase 1 → when inactivation of Na+ channels occur, there is opening of transient K+ channels causing a small, temporary repolarization
Phase 2 → L-type Ca2+ channels open when membrane is depolarized to -50mV allowing Ca2+ to flow in to the cell. The influx of calcium matches the efflux of potassium in this stage causing membrane potential to remain relatively constant
Phase 3 → outwardly rectifying K+ channels open during phase 3 whereas Na+ and Ca2+ channels become fully inactivated, this causes rapid repolarization
Phase 4 → resting membrane potential which is maintained by inward rectifying K+ channels which permit outflux of K+ at negative potentials and there is the reactivation of sodium channels


4. What is the refractory pd?

Absolute refractory pd → depolarization is not possible
Relative refractory pd → after partial but incomplete repolarization, depolarization can be possible, but occur slowly


5. What are the different phases of “Slow response” cardiac action potentials?

Phase 0 → depolarization by L-type Ca2+ channels
Phase 3 → repolarization
Phase 4 → spontaneous depolarization


6. What are the different categories of arrhythmias?

1. tachycardia
2. bradycardia
3. fibrillation (asynchronously)
4. supraventricular (atrial or AV junctional)
5. ventricular


7. What is an afterdepolarization?

Occurs when a normal action potential triggers abnormal depolarizations that reach threshold causing a secondary upstroke that can propagate and create abnormal rhythms. There are two types of afterdepolarizations: early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs).
EADs → occur during phase 2 (due to inward Ca2+ current) or phase 3 (partially recovered Na+ channels conducting an inward Na+ current) – these EADs cause a prolonged cardiac AP leading to torsades de pointes (arrhythmias)
DADs → interruption in phase 4 post repolarization [mechanism not well understood]


8. What are re-entry tachyarrhythmias?

Post MI, there is a dead zone in the myocardium that prevents conduction of electrical impulses of the myocytes, but allows conduction through them without the stimulation. Once the AP moves through, it is unable to move back through creating a unidirectional blockade. If APs can continue to be assed through this is called “re-entry” AP where the healthy myocardium is being reactivated.


9. What are the different types of arrhythmias beginning in the SA node through the ventricles?

1. SA node dysfunction → slow heart rhythm due to abnormal SA node [tx requires pacemaker]
2. Premature atrial contraction → early extra beats originating in the atria [do not require tx]
3. Atrial fibrillation → irregular heart rhythm resulting in atria contracting abnormally
4. Atrial flutter → arrhythmia caused by one or more rapid circuits in the atrium
5. Premature ventricular contractions (PVCs) → skipped beats due to stress, exercise, nicotine, etc [no treatment required]
6. Paroxysmal supraventricular tachycardia (PSVT) → rapid heart rate with regular rhythm originated from above the ventricles [two types: accessory path or AV nodal re-entry]
7. V-tach → rapid heart rhythm originating from ventricles [tx required immediately]
8. V-fib → erratic, disorganized firing of impulses from ventricles [medical emergency]


10. What are the different non-drug antiarrhythmic therapies?

1. Electrical cardioversion → electrical shock to re-synchronize the heart and reset normal rhythm
2. Pacemaker → small electrical impulses to heart muscle to maintain suitable heart rate
3. Implantable cardioverter-defibrillator (ICD) → tx V-tach and V-fib that delivers energy to reset heart
4. Catheter ablation → tx PSCTs, atrial flutter, a-fib and other tachycardias by disconnecting abnormal pathways


11. What are the goals of antiarrhythmic drugs?

1. termination of ongoing arrhythmia
2. prevention of arrhythmia


12. What is the goal to treatment of abnormal automaticity?

Decrease slow of phase 4 depolarization or raise the threshold of discharge to a less negative voltage thereby decreasing frequency of discharge


13. What is the goal to treatment of re-entrant circuits?

Slow conduction and/or increase refractory pd


14. What is the goal to treatment of afterdepolarizations?

Slowing conduction and/or increasing refractory pd making cells less excitable


15. What are the different classes of drugs used to treat Arrhythmias?

1. Class I → Na+ channel blockers
a. Class IA → quinidine, procainamide, disopyramide
b. Class IB → lidocaine, mexiletine
c. Class IC → flecainide, propafenone
2. Class II → B-blockers – propranolol, metoprolol, esmolol
3. Class III → K+ channel blockers – Amiodarone, Sotalol, dofetilide
4. Class IV → Ca2+ channel blockers – verapamil, diltiazem
5. Miscellaneous → digoxin, Magnesium, atropine, adenosine


16. What is the role of Class I antiarrhythmic drugs?

Modulate or block sodium channels thereby inhibiting phase 0 depolarization. By blocking Na+ channels it leaves fewer channels available to open in response to membrane depolarization thereby slowing the rate. During tachyarrhythmias, there is less time for the drug to dissociate thereby increasing amt of blocked channels.
Class IA drugs are intermediates in terms of speed of binding and dissociate from the receptor. Class IB drugs have the most rapid binding and dissociate from the receptor. Class IC drugs have the slowest binding and dissociate from the receptor.
Class I drugs do not have a direct effect on nodal tissue b/c it does not rely on fast Na+ channels for depolarization.


17. What does Use/state-dependence mean?

Drug binds more rapidly to open or inactivated Na+ channels thereby have greater effect in tissues more frequently depolarizing. Basically this means that cells discharging at abnormally high frequency are preferentially blocked.


18. What drugs fall under class IA anti-arrhythmic drugs and what is their mechanism?

Quinidine, Procainamide, Disopyramide
1. Slow rate of change in phase 0 → slowing conduction, prolonging AP and increasing ventricular effective refractory pd (Na+ channel block causing a slower depolarization therefore increased QRS (interval?))
2. Prolonged phase 3 → inhibition of K+ channels (increase QT causing prolonged repolarization)
3. Immediate speed of association with activated/inactivated Na+ channels and intermediate rate of dissociation
4. These are not commonly used anymore but rather are tested on their side effects


19. What the role of Quinidine in arrhythmias?

Quinidine is a Class IA anti-arrhythmic, used to suppress SVT and v-arrhythmias. It is NEVER THE DRUG OF CHOICE! It has concomitant class III activity by blocking K+ channels along with Na+ channels, is pro-arrhythmic and has since been replaced by calcium antagonists due to its toxicity. Quinidine has rapid ORAL absorption that forms active metabolites through CYP3A4 and inhibits CYP2D6, 3A4 and P-glycoprotein.


20. What are the adverse side effects of Quinidine as a tx for arrhythmias?

1. arrhythmias → torsades de pointes
2. SA and AV block
3. Nausea, vomiting, diarrhea
4. Thrombocytopenic purpura
5. Toxic doses cause V-tach that is exacerbated by hyperkalemia
6. Cinochonism (blurred vision, tinnitus, headache, psychosis)
7. Mixed a-adrenergic block and antimuscarinic properties
8. Can increase [digoxin] by decreasing renal clearance


21. What are the contraindications for Quinidine?

Do not use in pts with complete heart block. Use with extreme caution in pts with (1) prolonged QT interval, (2) hx of torsades de points, (3) incomplete heart block, (4) uncompensated HF, (5) myocarditis, (6) severe myocardial damage.


22. What is the mechanism of action of Procainamide in arrhythmias?

Procainamide is a class IA anti-arrhythmic use to suppress SVT and V-arrhythmias. It is a derivative of the local anesthetic procaine. It should only be used in life-threatening arrhythmias due to its proarrhythmic effects. It is similar to Quinidine in that it….
1. blocks Na+ channels in activated state
2. blocks K+ channels
3. has antimuscarinic properties
It is administered via IV, metabolized by CYP 2D6 and partly acetylated to NAPA (N-acetylprocainamide) which prolongs duration of AP (similar to class III).


23. What are the adverse effects of Procainamide?

There is a high incidence of adverse side effects with chronic use of Procainamide. Some of these effects are (1) reversible lupus-like syndrome, (2) asystole, induction of V-arrhythmias [when given at toxic doses], (3) CNS effects (depression, hallucination, psychosis), (4) weak anticholinergic effects, (5) hypotension.


24. What are the contraindications of Procainamide?

1. hypersensitivity
2. complete heart block
3. 2nd degree AV block
4. SLE
5. Torsades de pointes
6. Heart failure and HTN


25. What is the mechanism of action of Disopyramide in arrhythmias?

Disopyramide is a class IA antiarrhythmic used to suppress SVT and ventricular arrhythmias. It has strong inotropic effects, strong antimuscarinic properties, and causes peripheral vasoconstriction – all of these are considered negative effects. It also blocks the K+ channels prolonging the AP repolarization.


26. What are the adverse effects of Disopramide?

1. pronounced negative inotropic effects (decrease in Myocardial Ca2+)
2. severe antimuscarinic effects → dry mouth, urinary retention, blurred vision, constipation
3. may induce hypotension and cardiac failure without pre-existing myocardial dysfunction


27. What drugs fall under class IB anti-arrhythmic drugs and what is their mechanism?

Lidocaine, Mexiletine
These drugs cause a slow phase 0 by blocking Na+ channels (prolonged QRS), a decreased slope of phase 4, and a shortened phase 3 repolarization (shortened QT interval). Shortened phase 3 is opposite to the prolonged phase 3 produced by Class IA antiarrhythmics. There is little effects of these drugs on depolarization phase of AP in normal cells and there is rapid association and dissociation with Na+ channels.


28. What is the mechanism of action of Lidocaine as a anti-arrhythmias?

Lidocaine is a Class IB anti-arrhythmic drug that is used to treat ventricular arrhythmias from MI or cardiac manipulation (surgery). It is more effective on ischemic or diseased tissue and has little effect on K+ channels. There is little effect on atrial or AV junction arrhythmias. It is only given via IV b/c of the extensive 1st pass metabolism and is also used as a local anesthetic. The use of Lidocaine for VT has declined as IV amiodarone has been shown to be superior.


29. What are the adverse side effects of Lidocaine for arrhythmias?

1. wide toxic-therapeutic ratio
2. CNS effects (drowsiness, slurred speech, agitation)
3. Little impairment of LV function
4. NO negative inotropic effect
5. Cardiac arrhythmia
6. Toxic doses → convulsions, coma


30. What is the mechanism of action of Mexiletine as an anti-arrhythmias?

Mexiletine is a Class IB anti-arrhythmic drug that is an orally active derivative of lidocaine that can be used both orally and via IV. It is used to manage severe ventricular arrhythmias and has adverse effects on the CNS and GI system.


31. What drugs fall under class IC anti-arrhythmic drugs and what is their mechanism?

Flecainide, Propafenone
These drugs markedly depress phase 0 of AP by blocking sodium influx. There is marked slowing of conduction of AP but little effect on duration of ventricular effective refractory pd. These drugs associate and re-associate slowly with Na+ channels and show effects even at normal heart rates. No change in repolarization and very prolonged QRS interval. For people with structural heart disease, Flecainide and Propafenone are associated with fatal ventricular arrhythmias.


32. What is the mechanism of action of Flecainide as an anti-arrhythmias?

Flecainide is a Class IC anti-arrhythmic drug used to treat severe symptomatic ventricular and supraventricular arrhythmias, premature ventricular contraction, or ventricular tachycardia resistant to other therapy. It can also be used to prevent paroxysmal a-fib.


33. What are the adverse effects of Flecainide tx for arrhythmias?

1. negative inotropic effect (aggravates CHF)
2. CNS effects → dizziness, blurred vision, headache
3. GI effects → nausea, vomiting, diarrhea
4. Life threatening arrhythmias and V-tach


34. What is the mechanism of action of Propafenone as an anti-arrhythmias?

Propafenone is a Class IC anti-arrhythmic drug used in the treatment of life-threatening ventricular arrhythmias and for the maintenance of normal sinus rhythm in pts with symptomatic atrial fibrillation.


35. What are the adverse effects of Propafenone tx for arrhythmias?

1. negative inotropic effect (aggravates CHF)
2. CNS effects → dizziness, blurred vision, headache
3. GI effects → nausea, vomiting, diarrhea
4. Life threatening arrhythmias and V-tach
5. B-blocking activity leading to bronchospasm, aggravation of underlying HF, etc