Heart Failure and Antidysrhythmics

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Heart Failure and Antidysrhythmics

• Pharmacology
• NUR 3703
• By Linda Self

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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

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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

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Cardiac Action Potential

• Fast responseseen 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

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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

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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
• ResultCAD, hypertension leading to heart failure

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Other Causes of Heart Failure

• Hyperthyroidism
• Fluid overload
• Certain anti-dysrhythmic drugs
• Drugs that cause excessive retention of sodium
  and water

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Compensatory Mechanisms of the Heart

• COSV x HR
• Increased sympathetic activity and neurohormones
• Blunted baroreceptors
• Abundance of endothelin (vasoconstriction)
• RAASgtgtgtgtincreases preload and afterload
• Stretching, hypertrophy, ventricular remodeling
  and progressive deterioration

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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

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Classification of Heart Failure

• Class Iordinary activity does not cause S/S
• Class IIslight 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 IVany physical activity results in
  discomfort, s/s at rest.

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Drugs Used to Treat Heart Failure

• Inotropesstrengthen myocardial contraction and
  increase cardiac output. Digoxin, Dobutrex,
  Natrecor, Primacor
• ACE inhibitorsdrugs 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

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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 Blockersdecrease 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), Inderal
  propranolol)

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Drugs Used in Heart Failure

• Diureticsused 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)

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Drugs Used in Heart Failure

• Aldosterone Antagonistsused 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.

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Drug Therapy for Heart Failure

• VasodilatorsACEs 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.

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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.

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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
• Digitalize6-8 doses q6-8h
• Elimination is one week
• Digibind

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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.

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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

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Endothelin Receptor AntagonistsTracleer
(bosentan)

• Causes smooth muscle relaxation by targeting
  endothelin
• May reverse hypertrophy
• FDA approved for treatment of pulmonary
  hypertension

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Catecholamines

• Dobutrexsynthetic 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.
• Epinephrinenaturally occurring catecholamine.
  Low doses stiumulates beta receptors increasing
  CO by increasing rate and force of contraction.
  Can cause excessive stimulation, decreased renal
  blood flow.

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Principles of Therapy

• Acute heart failureIV loop diuretic, inotrope
  (digoxin, dobutamine, Primacor) vasodilators
  (nitroprusside, nitroglycerine or hydralazine)
• If decompensatingNatrecor. Monitor potassium
  levels closely.
• Chronic heart failureACEI or ARB, diuretic,
  digoxin, BB and/or Spironolactone, possibly
  potassium supplement

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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

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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

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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

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Automaticity

• Hearts 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

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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 nodescells 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)

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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

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Conductivity

• Ability of cardiac tissue to transmit electrical
  impulses
• SAgtgtinternodal tracts gtgt Atrial
  contractiongtgtAV nodegtgtBundle of Hisgtgtgtright and
  left bundle branchesgtgtgtgtPurkinje
  fibersgtgtgtventricular contraction

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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

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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 conditionsmay be 2ndary to hypoxia,
  ischemia, lyte imbalance, acid-base disturbances

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Cardiac Dysrhythmias cont.

• Re-entrythe 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.

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Dysrhythmias

• Mild or severe
• Acute or chronic
• Continuous or episodic
• Significant if interfere with hearts function
• Categorized by rate, location or patterns of
  conduction

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Types of Dysrhythmias

• Sinus dysrhythmiassinus tach, sinus brady
• Atrial dysrhythmiasatrial tach, atrial
  fibrillation (most common dysrhythmia), atrial
  flutter
• Junctional dysrhythmiasjunctional rhythm,
  junctional tach
• Ventricular dysrhythmias (Vtach, Vfib, Torsades)
• Heart blocks1st degree, 2nd degree (Mobitz Types
  1 and 2), 3rd degree heart block

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Antidysrhythmics

• Mechanism of action
• Reduce automaticity
• Slow conduction
• Prolong refractory period

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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

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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

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Class 1Atreatment 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.

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Class IB

• Xylocaine (lidocaine)drug of choice in treating
  serious ventricular dysrhythmias w/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 tx
  dysrhythmias caused by dig toxicity.Decreases
  automaticity and improves conduction through AV
  nodes. Helps with dysrhythmias and enhanced
  conduction can improve cardiac function.

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Class IC

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

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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 supraventricular tachydysrhythmias.
• Reduce mortality
• Sectral (acebutolol) cardioselective, Brevibloc
  (esmolol) B1 selective, Inderal (propranolol),
  Betapace (sotalol) also with Class III properties

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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

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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

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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.

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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 supraventricular tachycardias.
• Cardizem (diltiazem) and Calan (verapamil).
  Contraindicated in dig toxicity.
• Do not use IV verapamil with IV propranolol. Can
  cause fatal bradycardia and hypotension.

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Unclassified

• Adenosinedepresses 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 sulfateprevention 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.

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Principles of TherapyTreatment of
Supraventricular tachydysrhythmias

• 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
  dysrhythmiamay try to convert or manage rate
• For pharmacologic conversion of Afibadenosine,
  Corvert, verapamil or diltiazem

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Principles of Therapy-cont.

• Low dose amiodarone is drug of choice for
  preventing recurrent AF after cardioversion
• Drugs to slow heart rateamiodarone, beta
  blockers, digoxin, verapamil, diltiazem
• Adenosine, Corvert, verapamil or diltiazem may be
  used to convert PSVT to NSR.

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Principles of TreatmentVentricular Dysrhythmias

• Beta blocker may be first line
• Amiodarone (IV/PO), Tambocor (PO), Rythmol (PO)
  and Betapace (PO)are indicated in
  life-threatening ventricular dysrhythmias
• Lidocaine may be used in clients with
  structurally normal hearts. Also in digoxin
  induced ventricular dysrhythmias.

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