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Anti-Arrhythmic Agents PRCL 628: Medical Pharmacology Robert J. DiDomenico, PharmD , FCCP Clinical Associate Professor PowerPoint Presentation
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Anti-Arrhythmic Agents PRCL 628: Medical Pharmacology Robert J. DiDomenico, PharmD , FCCP Clinical Associate Professor

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Anti-Arrhythmic Agents PRCL 628: Medical Pharmacology Robert J. DiDomenico, PharmD , FCCP Clinical Associate Professor - PowerPoint PPT Presentation

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Anti-Arrhythmic Agents PRCL 628: Medical Pharmacology Robert J. DiDomenico, PharmD , FCCP Clinical Associate Professor
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  1. OBJECTIVES For each of the anti-arrhythmic drugs, students should be able to: Describe the mechanism of action. Compare and contrast the pharmacokinetic and drug interaction profiles within each class. Compare and contrast the clinical effects. List the common and/or serious adverse effects. Anti-Arrhythmic AgentsPRCL 628: Medical PharmacologyRobert J. DiDomenico, PharmD, FCCP Clinical Associate ProfessorCardiovascular Clinical Pharmacist

  2. Required Reading: Hume JR, Grant AO. Chapter 14. Agents Used in Cardiac Arrhythmias. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12th ed. New York: McGraw-Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=55822293. Suggested Reading: Sampson KJ, Kass RS. Chapter 29. Anti-Arrhythmic Drugs. In: Knollmann BC, ed. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011. http://www.accessmedicine.com/content.aspx?aID=16668361. Anti-Arrhythmic AgentsPRCL 628: Medical Pharmacology

  3. “Antiarrhythmic drugs are toxins with occasional therapeutic side effects” • Peter Buttrick, MD

  4. Sampson KJ, Kass RS. Chapter 29. Anti-Arrhythmic Drugs. In: Knollmann BC, ed. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011. http://www.accessmedicine.com/content.aspx?aID=16668361.

  5. Mechanisms of Arrhythmias

  6. Mechanisms of ArrhythmiasEnhanced Automaticity • Susceptible tissues include SA & AV nodes, His-Purkinje system, & cells that lack spontaneous pacemaker activity (e.g., ischemic ventricular cells) • Stimuli • Beta-adrenergic stimulation • Hypokalemia • Mechanical stretch

  7. Mechanisms of ArrhythmiasTriggered Activity Sampson KJ, Kass RS. Chapter 29. Anti-Arrhythmic Drugs. In: Knollmann BC, ed. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011. http://www.accessmedicine.com/content.aspx?aID=16668361.

  8. Mechanisms of ArrhythmiasRe-Entry Sanoski CA, Bauman JL. Chapter 25. The Arrhythmias. In: Wells BG, ed. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7972803.

  9. Pharmacologic Approaches to Terminating Tachyarrhythmias • Decrease automaticity of ectopic foci • Facilitate conduction (shorten refractory period) in an area of unidirectional block • Depress conduction (prolong refractory period) in either part of the re-entry circuit

  10. http://www.cvpharmacology.com/antiarrhy/sodium-blockers.htm

  11. Pharmacology of Antiarrhythmic Drugs

  12. Pharmacology of Antiarrhythmic Drugs

  13. Pharmacology of Antiarrhythmic Drugs

  14. http://www.cvpharmacology.com/antiarrhy/potassium-blockers.htmhttp://www.cvpharmacology.com/antiarrhy/potassium-blockers.htm

  15. Pharmacology of Antiarrhythmic Drugs

  16. Sanoski CA, Bauman JL. Chapter 25. The Arrhythmias. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7972803. Accessed August 7, 2013.

  17. ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation. J Am CollCardiol2001;38:1266.

  18. CAST Investigators. N Engl J Med 1989;321:406-12.

  19. Risk Factors for Ventricular Proarrhythmia with Antiarrhythmic Drugs

  20. Examples of QTc Prolonging Drugs • Psychotropics • Haloperidol • Risperidone • Ziprasidone • Olanzapine • Quetiapine • Antidepressants • SSRIs • Tricyclic antidepressants • Anti-infectives • Macrolide antibiotics • Quinolone antibiotics • Bactrim • Azoleantifungals • Methadone • Quinine • Promethazine • Tacrolimus http://www.crediblemeds.org/everyone/composite-list-all-qtdrugs/

  21. Bauman JL. Eur Heart J2001;3:K93-K100.

  22. Common Antiarrhythmic Drug Interactions • Avoid/Contraindicated • QTc prolonging drugs • Amiodarone, Dronedarone • Strong CYP3A4 inhibitors • Dofetilide • Verapamil • Cimetidine • Hydrochlorothiazide • Trimethoprim • Propafenone, Flecainide • HIV protease inhibitors • Use caution • Amiodarone, Dronedarone • Warfarin • Statins • Digoxin • Propafenone • Strong CYP2D6 inhibitors • Moderate CYP3A4 inhibitors • Flecainide • Moderate/strong CYP2D6 inhibitors • Itraconazole • Ketoconazole • Prochlorperazine • Megestrol

  23. Antiarrhythmic Drug Selection for Maintaining Normal Sinus Rhythm No/Minimal Structural Heart Disease Hypertension Coronary Artery Disease Heart Failure Substantial LVH ≠ LVH Dronedarone Flecainide Propafenone Sotalol Amiodarone Amiodarone Dofetilide Dofetilide Sotalol Amiodarone Dofetilide Catheter Ablation Amiodarone Dofetilide Catheter Ablation Wann LS, et al. Circulation 2011;123:104-23.