1. Pharmacology of Antidysrhythmic and Vasoactive Medications Tintinalli: Chapter 29 Lecture prepared by Jack Hay, DO

2. Class I Antidysrhythmics Lidocaine (Xylocaine) Procainamide (Pronestyl) Propafenone (Rythmol) Flecainide (Tambocor)

3. Lidocaine (Class Ib) Binds fast sodium channels, inhibiting recovery after repolarization Suppresses spontaneous depolarization of the ventricles during diastole Acts on ischemic myocardium

4. Lidocaine Onset of action: 45-90 seconds Indications : Ventricular dysrhythmias and ectopy Sinus maintenance after pulseless VT/VF Second-line for hemodynamically stable VT

5. Lidocaine Dosing: Load 1-1.5 mg/kg, max of 3 mg/kg Infuse at 1-4 mg/min (maintenance usually 2 mg/min) Adverse effects: Above 9 mg/min, may cause CNS depression, seizures, respiratory depression

6. Procainamide (Class Ia) Prevents ectopic or reentrant dysrhythmias Anticholinergic properties in large doses Potentially pro-dysrhythmic Prolonged QRS and QT intervals, PVCs, VT, VF, complete AV block Beware hypotension secondary to peripheral vasodilation

7. Procainamide Onset: 5-10 min Indications: Recurrent ventricular dysrhythmias stable VT & wide complex tachycardia Pulseless VT/VF Converting PSVT, a fib, a flutter

8. Procainamide Contraindications: Torsades & all blocks except first degree Myasthenia gravis (will increase weakness) Dosing: Load 20 mg/min up to 17 mg/kg then infuse at 1-4 mg/min to maintain suppression

9. Class II Antidysrhythmics BETA BLOCKERS Treatment of hypertension Decrease morbidity and mortality: Acute MI (metoprolol and atenolol) CHF (metoprolol and carvedilol)

10. Beta Blockers Cardioselective (specific for β1 receptors): atenolol, esmolol, metoprolol Useful with asthma, COPD, or diabetes Cardioselectivity lost at high doses

11. Labetalol (Normodyne) Non-cardioselective β-blocker and selective α1-adrenergic blocker The β-blocker effects exceed the α1- blocking effects at a 7:1 ratio if given IV Decreases heart rate, contractility, cardiac output, cardiac work, and peripheral resistance

12. Labetalol Onset: 2-5 min; duration 2-4 hrs Indications: HTN in patients with myocardial ischemia Minimally changes heart rate and cardiac output Acute neurological emergencies little effect on cerebral perfusion pressure or ICP

13. Labetalol Dosing: IV bolus 20 mg, repeat 40-80 mg q10 min prn up to 300 mg Infuse 0.5-2 mg/min to desired effect Adverse effects: orthostatic hypotension, heart failure, lethargy, increased liver enzymes

14. Class III Antidysrhythmics Amiodarone (Cordarone) Dofetilide (Tidosyn) Ibutilide (Corvert)

15. Amiodarone Inhibits sodium channels and β-adrenergics Prolongs action potential duration & effective refractory period  delays repolarization Impairs SA and AV nodal function and prolongs refractory period in accessory pathways

16. Amiodarone Indications: Ventricular and supraventricular dysrhythmias Recurrent VF and VT, atrial fib/flutter, and junctional & wide-complex tachycardias Pulseless VT/VF and atrial dysrhythmias with LVEF<40%

17. Amiodarone Dosing : Pulseless VT/VF: Load 300 mg IV, repeat 150 mg IV Other dysrhythmias: Load 150 mg IV, then infuse 1 mg/min X 6 hours, then 0.5 mg/min thereafter Adverse effects : Hypotension, bradycardia, asystole, cardiac arrest, shock Contains iodine – avoid if allergic to iodine or shellfish

18. Class IV Antidysrhythmics: Calcium Channel Antagonists Diltiazem (Cardizem) Verapamil (Verelan, Calan, Isoptin)

19. Diltiazem 1) Interferes slow channel extracellular calcium influx in cardiac smooth muscle 2) Inhibits sodium influx through fast channels Slows AV nodal conduction/prolongs refraction Dilates coronary vasculature  decreases O 2 consumption/ improves O 2 delivery

20. Diltiazem Onset: 2-3 min IV; 15-60 min PO Indications : Rapid conversion of PSVT to NSR Ventricular slowing in atrial fib/flutter Do NOT use for wide-complex tachydysrhythmias suggesting an accessory bypass tract (i.e. WPW syndrome)

21. Diltiazem Dosing: Load 0.25 mg/kg (max 20 mg) IV push over 2 min, repeat in 15 minutes with 0.35 mg/kg (max 25 mg) IV push over 2 minutes if patient not responsive Infuse at 5 mg/hr (max 15 mg/hr) Adverse effects: Angina, bradycardia, asystole, CHF, AV block, bundle branch block, hypotension, peripheral edema

22. Verapamil Action & Adverse Effects similar to Diltiazem Indications : As in Diltiazem Essential HTN Avoid in WPW patients (may accelerate bypass tract conduction) Dosing : For PSVT: 5-10 mg IV push over 2 min

23. Other Dysrhythmics/Vasoactives Adenosine Digoxin Atropine Dobutamine Vasopressin

24. Adenosine (Adenocard) Transient AV nodal block  breaks re-entrant circuit of AV nodal atrial tachydysrhythmia  No effect on non-AV nodal re-entrant SVTs or anterograde conduction over accessory pathways in WPW As rapid IV bolus - slows cardiac conduction and restores sinus rhythm Infused - acts as a potent vasodilator.

25. Adenosine Onset: 20-30 seconds; Half-life <10 seconds Indications: Emergency treatment of SVT Distinguish Afib/AFlutter from other tachydysrhythmias Contraindications: 2 nd and 3 rd degree AV block or sick sinus syndrome

26. Adenosine Dosing: 6 mg rapid IV bolus, most proximal port then 12 mg rapid IV bolus every 1-2 min prn x2 doses Follow bolus immediately with 10-20 cc flush Adverse effects (usu. minor and well-tolerated) Dyspnea, syncope, vertigo, metallic taste, flushing, chest pain, bradycardia, and sense of impending doom. Bronchospasm in asthmatics.

27. Digoxin 3 basic actions : Positive inotrope = Increases force, strength, and velocity of contractions Negative chronotrope = Slows heart rate, improving coronary blood flow and myocardial perfusion Negative dromotrope = Slows conduction velocity through AV node

28. Digoxin Inhibits Na + K + ATPase pump  gain of intracellular Na + Extra Na + removed via Na + Ca 2+ exchange channel Increased intracellular Ca 2+ improves myocyte contractility Onset: 5-30 min IV; 30-120 min PO

29. Digoxin Indications: Improve cardiac output in CHF Control ventricular response in atrial fib/flutter and PSVT

30. Digoxin Dosing : 10-15 μg/kg or 0.75-1.5 mg IV 0.125-0.5 mg/day PO Adverse effects : GI: abdominal pain, N/V, diarrhea Cardiac: sinus bradycardia, AV or SA nodal block, ventricular dysrhythmias

31. Digoxin Toxicity : Can be fatal if not properly treated Symptoms are varied and can be vague Altered mentation, visual disturbances, seizures PVCs, VT, junctional tachycardia, high-degree AV block, SVT, and sinus arrest Hyperkalemia

32. Digoxin Toxicity Treatment : Lidocaine, phenytoin and/or atropine Digibind (antibody fragments) IF: Tachydysrhythmias Sinus bradycardia Severe AV blocks K + >5mEq/L secondary to digoxin use

33. Atropine Antagonizes acetylcholine & muscarinic agents Increases sinus node automaticity and AV conduction by blocking vagal activity (parasympatholytic) Onset: 2-4 minutes Indications: Symptomatic sinus bradycardia PEA and asystole

34. Atropine Dosing : For bradycardia = 0.5mg IVP q 3-5min For PEA/asystole = 1mg IVP q 3-5min Maximum total dose of 0.04 mg/kg produces complete vagal blockade

35. Atropine Adverse effects : Dry mouth, CNS stimulation, hallucinations, blurred vision, and tachycardia Potential ischemia and ventricular tachydysrhythmia in hemodynamically stable bradycardic patients

36. Dobutamine (Dobutrex) Sympathomimetic - inotropic and chronotropic effects β1/ β2-adrenergic and α-adrenergic offset by α-adrenergic antagonist activity  increase in myocardial contractility and systemic vasodilation

37. Dobutamine Onset: 1-2 min Indications: Positive inotropic support for cardiovascular decompensation secondary to ventricular dysfunction or low-output heart failure. Preferred agent to manage cardiogenic shock.  increases CO and renal/mesenteric blood flow w/o direct stimulation of the heart rate.

38. Dobutamine Dosing : 2-20 μg/kg/min Monitor patient with CVP or pulmonary artery catheter. Adverse effects : Increases in heart rate, blood pressure, and ectopic dysrhythmias

39. Nitroglycerin Enters vascular smooth muscle Converts to nitric oxide direct vasodilator produces systemic venodilatation Venodilation at <100 μg/min Arteriolar vasodilation >200 μg/min

40. Nitroglycerin Indications : Angina pectoris Acute decompensated CHF Hypertensive crisis Perioperative hypertension in CV procedures Dosing : SL, lingually, intrabuccaly, topically or IV Multiple formulations with specific dosing regimens

41. Nitroglycerin Adverse effects: Headache, dizziness, hypotension, syncope Remove transdermal patches and ointments before defibrillation or cardioversion Concurrent use of sildenafil (Viagra) has been reported to cause excessive refractory hypotension

42. Vasopressin (Pitressin) Directly stimulates smooth muscle V1 receptors vasoconstriction Decreased splanchnic, coronary, GI, skin, and muscular system blood flow May be beneficial during resuscitation attempts

43. Vasopressin Onset = immediate Indications : Alternative to epinephrine as nonadrenergic peripheral vasoconstrictor during CPR Pulseless VT/VF

44. Vasopressin Dosing : Cardiac arrest: 40 units IV push single dose Epinephrine 1 mg IV should be given after 10 minutes if adequate response is not seen. Adverse effects: HTN, bradycardia, dysrhythmias, PACs, heart block, peripheral vascular constriction, and decreased cardiac output

45. Questions 1. Which of the following is indicated for symptomatic sinus bradycardia? A. Labetalol B. Atropine C. Neseritide D. Vasopressin E. Digoxin 2. Nitroglycerin may not be given: A. Sublingually B. Topically with cardioversion C. Via IV infusion D. With concomitant Viagra use E. B & D

46. 3. True or False? Amiodarone is a good treatment choice for wide-complex tachydysrhythmias in patients with unknown underlying EF. 4. Which of the following is false regarding adenosine? A. Is indicated for emergency treatment of SVT. B. Has a half-life of about 10 seconds. C. Blocks anterograde conduction over accessory pathways. D. Produces transient AV nodal block. E. A sense of impending doom is a common side effect. 5. What is the appropriate dose of vasopressin for pulseless VT/VF? A. 40 units IV push B. 1 mg IV C. 1mg/kg/min D. 6 mg rapid IV push E. 300 mg IV

47. Answers 1. B 2. E 3. T 4. C 5. A