Pharmacology of Antidysrhythmic and Vasoactive Medications

1. Pharmacology of Antidysrhythmic and Vasoactive Medications dr shabeel pn

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 O2 consumption/ improves O2 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: • 2nd and 3rd 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+Ca2+ exchange channel • Increased intracellular Ca2+ 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