Heart Failure and Antidysrhythmics

1. Heart Failure and Antidysrhythmics Pharmacology NUR 3703 By Linda Self

2. Review of Heart • Unique properties of heart: • Contractility • Conductivity • Excitability

3. Layers of Heart • Pericardium • Myocardium • epicardium

4. Conduction of the Heart • SA node • Internodal tracts • AV node/junction • Bundle of His • Right and left bundles • Purkinje fibers

5. Cardiac action potential • Fast sodium channels account for spike-like rapid onset of action potential • Slower calcium-sodium channels responsible for plateau • Potassium channels which are responsible for repolarization phase and return of membrane to the resting potential

6. Cardiac Action Potential • Fast response—seen in atrial and ventricular muscle cells and Purkinje conduction system, uses fast sodium channels • Low response of SA and AV nodes, use slow calcium channels

7. Drug Therapy for Heart Failure • Occurs when heart cannot pump enough blood to meet tissue needs for oxygen and nutrients • May be impaired contraction (systolic dysfunction) • May be impaired relaxation and filling of ventricles (diastolic dysfunction) • May be both

8. Causes of Heart Failure • Dysfunction of contractile myocardial cells and endothelial cells • Endothelium dysfunction results in build-up of atherosclerotic plaque, growth of cells, inflammation and activation of platelets • Result—CAD, hypertension leading to heart failure

9. Other Causes of Heart Failure • Hyperthyroidism • Fluid overload • Certain anti-dysrhythmic drugs • Drugs that cause excessive retention of sodium and water

10. Compensatory Mechanisms of the Heart CO=SV x HR • Increased sympathetic activity and neurohormones • Blunted baroreceptors • Abundance of endothelin (vasoconstriction) • RAAS>>>>increases preload and afterload • Stretching, hypertrophy, ventricular remodeling and progressive deterioration

11. Signs and Symptoms of Heart Failure (Varies with degree of failure & if right or left) • Shortness of breath with activity • Crackles in lungs • Ankle edema • JVD • Pink frothy sputum • Anxiety • Restlessness • Cough • Moist skin • Extremities may be cool and pale

12. Classification of Heart Failure • Class I—ordinary activity does not cause S/S • Class II—slight limitations, asymptomatic at rest. Activity does result in fatigue, palpitations, dyspnea or anginal pain • Class III-marked limitation of physical activity. Less than ordinary activity causes fatigue, palpitations, dyspnea or angina • Class IV—any physical activity results in discomfort, s/s at rest.

13. Drugs Used to Treat Heart Failure • Inotropes—strengthen myocardial contraction and increase cardiac output. Digoxin, Dobutrex, Natrecor, Primacor • ACE inhibitors—drugs of first choice in treating patients with chronic heart failure. Improve cardiac function, increase exercise tolerance and decrease ventricular remodeling. Decrease RAAS.Dilate veins and arteries, decrease workload and increase perfusion of body organs. Prinivil, Altace, Aceon,Capoten

14. Drug Used in Heart Failure • Angiotensin Receptor Blockers (ARBS)—block receptor site rather than inhibiting the conversion of angiotensin I to II. Diovan (valsartan) has received FDA approval for use in heart failure. Diovan (valsartan) • Beta Blockers—decrease morbidity and mortality in chronic HF. Suppress activation of sympathetic nervous system so ventricular remodeling. Usually used in conjunction with ACEs and diuretics. Toprol (metoprolol), Inderalpropranolol)

15. Drugs Used in Heart Failure • Diuretics—used in acute and chronic heart failure. Loop diuretics when degree of renal insufficiency present. Decrease plasma volume and increase excretion of sodium and water. Decreases preload. Lasix also has a vasodilatory effect thus decreasing afterload. Will also need meds to enhance cardiac contractility and vasodilation. Cautious administration and monitoring of potassium necessary. Others: Bumex , Demadex (torsemide)

16. Drugs Used in Heart Failure • Aldosterone Antagonists—used in moderate to severe heart failure. Increased aldosterone results in interstitial fibrosis, decreased systolic function and increased ventricular dysrhythmias. Spironolactone used along with an ACE inhibitor, loop diuretic and sometimes digoxin.

17. Drug Therapy for Heart Failure • Vasodilators—ACEs and ARBs have this effect. Also venous dilators such as nitrates Isordil, Imdur, decrease preload. Arterial dilators such as Apresoline(hydralazine), decrease afterload. Start low, discontinue slowly to avoid rebound vasoconstriction.

18. Inotropes Digoxin (Lanoxin)—cardiac glycoside. Therapeutic levels are 0.5-2.0 ng/mL (in renal failure and the elderly, therapeutic level is .5-1.3). Works by inhibition of Na, K-ATPase, enzyme affects sodium and calcium exchange after contraction, results in greater availability of calcium to activate actin and myosin w/ resultant increased cardiac contractility.

19. Digoxin • Has direct depressant effect on cardiac conduction tissues • Stimulates vagus nerve • Increased efficiency decreases compensatory tachycardia • Use in heart failure, Atrial fibrillation • Contraindicated in ventricular tachycardia, ventricular fibrillation, acute MI, Stokes-Adams, WPW, renal impairment and lyte imbalances • Digitalize—6-8 doses q6-8h • Elimination is one week • Digibind

20. Phosphodiesterase Inhibitors • Short term use in acute, severe heart failure that is not controlled by digoxin, diuretics and vasodilators • Increase cAMP by inhibiting phosphodiesterase (metabolizes cAMP) • Relax vascular smooth muscle so decrease preload and afterload • Inocor (amrinone) and Primacor (milranone) • Primacor long half-life, more potent than Inocor and has fewer side effects. • Side effects include: tachycardia, dysrhythmias, hypotension.

21. Human B Type Natriuretic PeptideNatrecor (nesiritide) • Identical to endogenous BNP which is secreted in ventricles in response to fluid and pressure overload • Reduces preload and afterload, increases diuresis and secretion of sodium, suppresses RAAS, and decreases secretion of norepinephrine and endothelin. • Administer in a separate line. • Hemodynamic monitoring is recommended • No adjustment in dosing r/t age, gender, race/ethnicity or renal function impairment

22. Endothelin Receptor AntagonistsTracleer (bosentan) • Causes smooth muscle relaxation by targeting endothelin • May reverse hypertrophy • FDA approved for treatment of pulmonary hypertension

23. Catecholamines • Dobutrex—synthetic catecholamine developed to act mainly on beta1 receptors in heart. Increases force of contraction w/o increasing heart rate. Given IV, rapid onset of action. • Epinephrine—naturally occurring catecholamine. Low doses stiumulates beta receptors increasing CO by increasing rate and force of contraction. Can cause excessive stimulation, decreased renal blood flow.

24. Principles of Therapy • Acute heart failure—IVloop diuretic, inotrope (digoxin, dobutamine, Primacor); vasodilators (nitroprusside, nitroglycerine or hydralazine); • If decompensating—Natrecor. Monitor potassium levels closely. • Chronic heart failure—ACEI or ARB, diuretic, digoxin, BB and/or Spironolactone, possibly potassium supplement

25. Effects of Herbal Supplements • Natural licorice blocks the effects of spironolactone and causes sodium retention and potassium loss • Hawthorn can increase effects of ACEIs and digoxin • Ginseng can result in digoxin toxicity

26. Antidysrhythmics • Used to prevent and manage cardiac dysrhythmias • Dysrhythmias (aka arrhythmias) are abnormalities in heart rate or rhythm • Can interfere with perfusion of body tissues

27. Cardiac Electrophysiology • Heart has specialized cells with intercalated discs • Electrical activity resides in specialized tissues that can generate and conduct an electrical impulse • Conductivity is much faster in heart tissue • Sequence: stimulation from impulse, transmission, contraction of atria and ventricles and relaxation of atria and ventricles

28. Automaticity • Heart’s ability to generate an electrical impulse • Can occur in any part of conduction system • SA node has highest degree of automaticity so highest rate of electrical discharge, thus, is primary pacemaker • Impulse dependent on sodium and calcium into a myocardial cell and potassium ions moving out of cardiac cells

29. Automaticity • Cardiac cell membranes more permeable to sodium, rapid influx, calcium follows • As Na+ and Ca++ move into cells, K+ moves out • Movement of ions changes membrane from resting state of neutrality to state of electrical buildup • When electrical energy is discharged (depolarized), muscle contraction occurs • SA and AV nodes—cells in SA and AV nodes depolarize in response to the entry of calcium ions rather than entry of sodium ions. Slower channels (slow depolarization). • Atrial and ventricular cells rely on sodium channels which are faster channels (rapid depolarization)

30. Automaticity cont. • Ability of a cardiac muscle cell to respond to electrical stimul is called excitability or irritability • After contraction, sodium and calcium ions return to extracellular space, potassium to intracellular, muscle relaxation occurs, cell prepares for next electrical stimulus • Following contraction, period of decreased excitability called absolute refractory period • As ions begin to return to original locations, before resting membrane potential is reached, stimulus greater than normal can cause early depolarization, this period is called the relative refractory period

31. Conductivity • Ability of cardiac tissue to transmit electrical impulses • SA>>internodal tracts >> Atrial contraction>>AV node>>Bundle of His>>>right and left bundle branches>>>>Purkinje fibers>>>ventricular contraction

32. Action Potential • +20 Phase 1 • 0 Phase 2 • -20 • -40 Phase 3 • -60 • -80 • -90 return to RMP • Na+ RMP Ca++ Ca++ K+ Na+ K+

33. Cardiac Dysrhythmias • Can originate in any part of conduction system • Result from disturbances in impulse formation or conduction defects • Abnormal impulse formation--Automaticity allows for other than the SA node to depolarize given certain conditions—may be 2ndary to hypoxia, ischemia, lyte imbalance, acid-base disturbances

34. Cardiac Dysrhythmias cont. Re-entry—the diversion of a repolarization wave from a direction in which it is blocked to another in which it is not. The wave then goes back up the original pathway to produce a contraction. This leads to a continuing series of premature beats.

35. Dysrhythmias • Mild or severe • Acute or chronic • Continuous or episodic • Significant if interfere with heart’s function • Categorized by rate, location or patterns of conduction

36. Types of Dysrhythmias • Sinus dysrhythmias—sinus tach, sinus brady • Atrialdysrhythmias—atrialtach, atrial fibrillation (most common dysrhythmia), atrial flutter • Junctionaldysrhythmias—junctional rhythm, junctionaltach • Ventricular dysrhythmias (Vtach, Vfib, Torsades) • Heart blocks—1st degree, 2nd degree (Mobitz Types 1 and 2), 3rd degree heart block

37. Antidysrhythmics • Mechanism of action: • Reduce automaticity • Slow conduction • Prolong refractory period

38. Indications • To convert Atrial fib or flutter to normal sinus rhythm • To maintain NSR after conversion from AF or flutter • When the ventricular rate is so fast or irregular that CO is impaired • When dangerous dysrhythmias occur and may be fatal if not terminated

39. Class I Sodium Channel Blockers • Block sodium into cells in conduction system • Is membrane stabilizing • Use is declining due to proarrhythmic effects • Used for supraventricular and ventricular dysrhythmias

40. Class 1A—treatment of PVCs, SVT and Vtach, prevention of V.fib. • Quinidine —prototype. Reduces automaticity, slows conduction and prolongs refractory period. Form of sulfate or gluconate. Latter has fewer GI SE. • Norpace (disopyramide). • Pronestyl (procainamide)—more SE than quinidine. Can cause lupus like syndrome.

41. Class IB • Xylocaine (lidocaine)—drug of choice in treating serious ventricular dysrhythmiasw/MI. Decreases automaticity in ventricles. Liver side effects, neuro side effects. • Mexitil (mexilitene)—oral analog of lidocaine with similar actions. Used to suppress ventricular fibrillation or v. tach. • Dilantin (phenytoin)—may be used to txdysrhythmias caused by dig toxicity.Decreasesautomaticity and improves conduction through AV nodes. Helps with dysrhythmias and enhanced conduction can improve cardiac function.

42. Class IC • Tambocor (flecainide) and Rythmol (propafenone)—decrease conduction in ventricles. Very proarrhythmic. Reserved for use only in those with life-threatening ventricular dysrhythmias.

43. Class II Beta-Adrenergic blockers • Antidysrhythmic by blocking sympathetic nervous system stimulation of beta receptors in heart and decreasing risks of ventricular fibrillation. • Useful in slowing ventricular rate of contraction in supraventriculartachydysrhythmias. • Reduce mortality • Sectral (acebutolol) cardioselective, Brevibloc (esmolol) B1 selective, Inderal (propranolol), Betapace (sotalol) also with Class III properties

44. Class III Potassium Channel blockers • Treatment of ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to sinus rhythm; maintenance of sinus rhythm • Prolong duration of action potential, slow repolarization and prolong refractory period in atria and ventricles • Associated with less ventricular fibrillation and decreased mortality

45. Class III Potassium Channel Blockers • Cordarone (amiodarone)—sodium channel blocker, beta blocker, calcium channel blocker and potassium channel blocker • IV slows conduction through AV node and prolonging refractory period • Used in ACLS for recurrent Vtach or fib and to maintain NSR after AF and flutter • Extensive liver metabolism, iodine rich so can affect thyroid, pulmonary fibrosis, corneal microdeposits, blue skin, photosensitivity • Very long acting, lasting up to weeks when taken orally

46. Class III Potassium Channel Blockers • Corvert (ibutilide)—drug enhances efficacy in cardioversion of Afib/flutter. Can result in Torsades. Administer in controlled settings only. • Betapace (sotalol)-beta adrenergic blocking and potassium channel blocking activity. Beta blocking effects at lower doses and class III predomination at higher doses. Prevention of Vtach and fib.

47. Class IV Calcium Channel Blockers • Block movement of calcium into conductile and contractile myocardial cells. • As antidysrhythmics, reduce automaticity of the SA and AV nodes, slow conduction and prolong the refractory period. • Effective only in supraventriculartachycardias. • Cardizem (diltiazem) and Calan (verapamil). Contraindicated in dig toxicity. • Do not use IV verapamil with IV propranolol. Can cause fatal bradycardia and hypotension.

49. Unclassified • Adenosine—depresses conduction at AV node and is used to restore NSR in PSVT. Ineffective in other dysrhythmias. Short half-life of 10 seconds. Give by rapid IV bolus. • Magnesium sulfate—prevention of recurrent torsades de pointes and management of digitalis induced dysrhythmias. Low Mg++ levels increases myocardial irritability and is risk factor for atrial and ventricular dysrhythmias.

50. Principles of Therapy—Treatment of Supraventriculartachydysrhythmias • Class I agents do not decrease mortality and use is declining. • Increased use of Class II and III because of decreased s/s and decreasing mortality • Beta blockers management of choice if rapid heart rate is causing angina • Atrial fibrillation is most common dysrhythmia—may try to convert or manage rate • For pharmacologic conversion of Afib—adenosine, Corvert, verapamil or diltiazem