Antiarrhythmics 2 Flashcards Preview

Pharm > Antiarrhythmics 2 > Flashcards

Flashcards in Antiarrhythmics 2 Deck (31):

1. What drugs fall under class II anti-arrhythmic drugs and what is their mechanism?

B-blockers [propranolol, metoprolol]
In the treatment of arrhythmias, these drugs reduce both HR and contractility via blocking B1 receptors. By reducing HR it slow the conduction of impulses (phase 4 prolonged) through the myocardial conducting system reducing the rate of spontaneous depolarization in cells with pacemaker activity (block adrenergic release). By prolonging the repolarization at the AV node, there is an increase in the PR interval. Most of the effect is on the nodal tissue and there is little effect on the AP in myocardial cells.


2. What the role of Propranolol and Metoprolol in arrhythmias?

Propranolol and Metoprolol are class II anti-arrhythmic drugs used to reduce the incidence of sudden arrhythmic death post MI. It also controls (does not stop!) SVT (atrial fib and flutter, AV nodal re-entrance tachy) as well as ventricular tachycardia (catecholamine-induced arrhythmias, digoxin toxicity).


3. What the role of Esmolol in arrhythmia tx?

Esmolol is a short acting B1 selective antagonist that falls in class II of the anti-arrhythmic drugs. It has a short half life of about 9 minutes therefore needs to be given via IV during tx of acute arrhythmias during surgery or emergencies.


4. What are the adverse effects of Class II anti-arrythmic drugs?

1. bradycardia, hypotension, CNS effects
2. contraindicated in acute CHF (b/c it decreases CO), severe bradycardia/heart block and severe hyperactive airway disease


5. What drugs fall under class III anti-arrhythmic drugs and what is their mechanism?

Amiodarone, Sotalol, Dofetilide
Class III anti-arrhythmic drugs are K+ channel blockers that block the repolarization of K+ channels thereby prolonging the AP (and QT interval) and effective refractory pd. There is no change in phase 0 or the resting membrane potential. Because there is a prolonging of the QT interval, there is a potential for these drugs to induce arrhythmias.


6. What the MOA of Amiodarone in arrhythmias?

Amiodarone is an anti-arrhythmic drug that falls primarly into class III, but has class I, II and IV effects as well. It is structurally related to thyroxine containing iodine and has a half life of several weeks. It can be administered orally or via IV and full clinical effects or adverse effect may take 6 weeks to achieve. Amiodarone…
1. decreases AV conduction and sinus node function
2. blocks mostly inactivated Na+ channels
3. acts as a weak Ca2+ channel blocker
4. inhibits adrenergic stimulation (a and B-blocking)
5. contains antianginal and antiarrhythmic activity
*unlike the other K+ blockers, there is a low incidence of Torsades de Pointes with Amiodarone.


7. What is the clinical application of Amiodarone in arrhythmia tx?

1. one of most commonly used antiarrhythmics
2. manages ventricular and supraventricular arrhythmias
3. drug of choice for acute VT refractory to cardioversion shock (??)
4. low doses can maintain normal sinus rhythm in pts with a-fib


8. What are the adverse effects of Amiodarone in the tx of arhythmias?

1. for over 50% of pts, long term use leads to adverse effects severe enough for the pts to discontinue the rug
2. interstitial pulmonary fibrosis
3. hyper- or hypo-thyroidism
4. photosensitivity
5. liver toxicity
6. tremor, ataxia, dizziness,
7. GI intolerance
8. Hypotension, bradycardia, neuropathy, AV block, arrhythmia
9. Blue skin discoloration due to iodine accumulation


9. What pts should NOT take Amiodarone?

Pts taking: digoxin, theophylline, warfarin, quinidine.
Pts with: bradycardia, SA or AV block, severe hypotension, severe respiratory failure.


10. What the MOA of Sotalol in arrhythmias?

Sotalol is a class III anti-arrhythmic drug that acts as a potent non-selective B-blocker and inhibits rapid outward K+ current. By blocking the K+ current there is prolongation of repolarization and the duration of the AP that leads to a lengthening of the refractory pd. Sotalol is used to treat life-threatening ventricular arrhythmias, maintain sinus rhythm in symptomatic pts.


11. What are the adverse effects of Sotalol in the tx of arrhythmias?

1. normal B-blocker effects
2. lowest rate of acute or long-term adverse effects compared to other antiarrhythmics
3. prolonged QT leads to Torsades de points
4. caution in pts with renal impairment


12. What the MOA of Dofetilide in arrhythmias?

Dofetilide is a Class III anti-arrhythmic drug that acts as a potent and pure K+ channel blocker. It can be used in conversion of a-fib/flutter to normal sinus rhythm or maintenance of normal sinus rhythm in pts with chronic a-fib/flutter. About 80% of Dofetilide is excreted in the non-metabolized parent form into the urine therefore the pt needs to have functional kidneys to avoid toxicity.


13. What are the adverse effects of Dofetilide in tx of arrhythmias?

1. headache
2. chest pain
3. dizziness
4. Ventrcular tachycardia
5. Prolonged AT interval developing to Torsades de Pointes


14. What drugs fall under class IV anti-arrhythmic drugs and what is their mechanism?

Verapamil, Diltiazem
Class IV anti-arrhythmic drugs are Ca2+ channel blockers that decrease the inward Ca2+ current thereby decreasing the rate of phase 0 depolarization. Ca2+ current determines conduction in SA and AV node, thereby when it is blocked the conduction in slowed. There is a prolonged PR interval as there is slowed conduction making it across the AV node. There are major effects on both vascular and cardiac SM.


15. What the MOA of Verapamil and Diltiazem in arrhythmias?

Verapamil and Diltiazem are class IV anti-arrhythmic drugs used to treat SVT and reduce ventricular rate in a-fib and flutter, and HTN and angina. These drugs block Ca2+ channels in the open and depolarized state [use/state-dependent] preventing repolarization. By prolonging repolarization there is a slowed conduction and prolonged effective refractory pd. By inhibiting the voltage-sensitive Ca2+ channels there is a decrease in slow inward current that triggers cardiac contraction.
These drugs cause decreased contractility (inotropy), decreased HR (chronotropy), and decreased conduction velocity (dromotorpy).
Verapamil → relatively selective for myocardium and less selective as systemic vasodilator
Diltiazem → intermediate selectivity for myocardium b/c Verapamil and Dihydropyridine


16. What are the adverse effects of Verapamil and Diltiazem in the tx of arrhythmias?

1. negative inotropics
2. transient decrease in BP
3. CNS effects (headache, fatigue, dizziness)
4. GI effects (constipation, nausea)
*These drugs are contraindicated with use of other CV drugs such as digoxin, dofetilide, simvastatin and lovastatin as they increase their concentration.


17. What is the effect of Digoxin on the tx of arrhythmias?

Digoxin shortens the refractory pd in atrial and ventricular myocardial cells BUT prolonges the effective refractory pd and diminished conduction velocity in the AV node. It therefore indirectly causes prolonged hyperpolarization. (??) It controls the ventricular response rate in a-fib/flutter with impaired LV function or HF.


18. What is the different in MOA of Digoxin in tx of HF versus arrhythmias?

HF → positive inotrope that increases intracellular [Ca2+]
Arrhythmias → direct AV node blocking effect and vagomimetic properties by inhibiting Ca2+ current in AV node and activation Ach-mediated K+ currents in the atrium


19. What is the result of toxic doses of Digoxin?

Ectopic ventricular beats → ventricular tachycardia → ventricular fibrillation


20. What is the effect of Adenosine in the tx of arrhythmias?

Adenosine is a naturally occurring nucleoside (half life of 15 seconds) that acts as a P1 receptor agonist. At high doses it decreases conduction velocity and prolongs refractory pd as well as decreases automaticity in AV node.
*This is the drug of choice for abolishing acute SVT
1. enhances K+ conductance
2. inhibits cAMP-mediated Ca2+ influx
3. cause hyperpolarization especially in the AV node


21. What are the adverse effects of Adenoside?

Flushing, burning, chest pain, hypotension, bronchoconstriction (in asthmatics)


22. What is the role of Magnesium in arrhythmia tx?

Magnesium is a functional Ca2+ antagonist thereby decreasing contractility (??). It is used in the treatment of Torsades de pointes, digitalis-induces arrhythmia, and prophylaxis of arrhythmia in acute MI.


23. What is the role of Atropine in arrhythmia tx?

Atropine is used in bradyarrythmias to decrease vagal tone.


24. Which anti-arrhythmics act on the SA and AV node?

B-Blockers (II), calcium-channel blockers (IV), digoxin


25. Which anti-arrhythmics act on the atrial myocytes?

Class IA, IC, and K+ channel blockers (III)


26. Which anti-arrhythmics act on the ventricular myocytes?

Na+ channel blocker (I) and K+ channel blocker (III)


27. Which anti-arrhythmics act on the accessory pathway in the heart?

Class IA and K+ channel blocker (III)


28. What are the treatment approaches to Atrial fibrillation?

1. Rhythm control → restore and maintain sinus rhythm [anticoagulation followed by synchronized direct current or drugs]
2. Rate control → control of ventricular rate while allowing atrial fibrillation to continue [use drugs that act on AV node to slow conduction]


29. What drugs/MOA of drugs are used to control RATE in a-fib?

1. Ca2+ channel blockers
2. B-blockers
3. Digoxin (in pts with reduced EF or CHF)
4. Amiodarone (when other agents can’t be used)


30. What drugs/MOA of drugs are used to control RHYTHM in a-fib?

Class IC anti-arrhythmics → Flecainide, propafenone
Class III anti-arrhythmics → amiodarone, dofetilide


31. What drugs are used to prevent thromboembolic events?

1. Heparin (IV)
2. Warfarin (oral)
**continue oral-anticoagulants for at least 4 weeks after procedure