Heart Failure and
Antidysrhythmics
Pharmacology
NUR 3703
By Linda Self
Review of Heart
• Unique properties of heart:
1. Contractility
2. Conductivity
3. Excitability
Layers of Heart
• Pericardium
• Myocardium
• epicardium
Conduction of the Heart
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SA node
Internodal tracts
AV node/junction
Bundle of His
Right and left bundles
Purkinje fibers
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
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
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
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
Other Causes of Heart Failure
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Hyperthyroidism
Fluid overload
Certain anti-dysrhythmic drugs
Drugs that cause excessive retention of sodium
and water
Compensatory Mechanisms of the
Heart
CO=SV x HR
1. Increased sympathetic activity and
neurohormones
2. Blunted baroreceptors
3. Abundance of endothelin (vasoconstriction)
4. RAAS>>>>increases preload and afterload
5. Stretching, hypertrophy, ventricular
remodeling and progressive deterioration
Signs and Symptoms of Heart Failure
(Varies with degree of failure & if right
or left)
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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
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.
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
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), Inderal propranolol)
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)
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.
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.
Inotropes
Digoxin (Lanoxin)—cardiac glycoside.
Therapeutic levels are 0.5-2.0 ng/mL (in renal
failure and the elderly, therapeutic level is .51.3).
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.
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
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.
Human B Type Natriuretic Peptide
Natrecor (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
Endothelin Receptor Antagonists
Tracleer (bosentan)
• Causes smooth muscle relaxation by targeting
endothelin
• May reverse hypertrophy
• FDA approved for treatment of pulmonary
hypertension
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.
Principles of Therapy
• Acute heart failure—IV loop 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
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
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
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
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
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)
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
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
Action Potential
• +20 Phase 1
•0
• -20
• -40
• -60
• -80
• -90
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Na+
RMP Ca++
Phase 2
Phase 3
return to RMP
Ca++
K+ Na+
K+
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
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.
Dysrhythmias
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Mild or severe
Acute or chronic
Continuous or episodic
Significant if interfere with heart’s function
Categorized by rate, location or patterns of
conduction
Types of Dysrhythmias
• Sinus dysrhythmias—sinus tach, sinus brady
• Atrial dysrhythmias—atrial tach, atrial
fibrillation (most common dysrhythmia), atrial
flutter
• Junctional dysrhythmias—junctional rhythm,
junctional tach
• Ventricular dysrhythmias (Vtach, Vfib,
Torsades)
• Heart blocks—1st degree, 2nd degree (Mobitz
Types 1 and 2), 3rd degree heart block
Antidysrhythmics
• Mechanism of action:
1. Reduce automaticity
2. Slow conduction
3. Prolong refractory period
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
Class I Sodium Channel Blockers
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Block sodium into cells in conduction system
Is membrane stabilizing
Use is declining due to proarrhythmic effects
Used for supraventricular and ventricular
dysrhythmias
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.
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.
Class IC
• Tambocor (flecainide) and Rythmol
(propafenone)—decrease conduction in
ventricles. Very proarrhythmic. Reserved for
use only in those with life-threatening
ventricular dysrhythmias.
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
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
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
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.
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.
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.
Principles of Therapy—Treatment 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
dysrhythmia—may try to convert or manage rate
• For pharmacologic conversion of Afib—
adenosine, Corvert, verapamil or diltiazem
Principles of Therapy-cont.
• Low dose amiodarone is drug of choice for
preventing recurrent AF after cardioversion
• Drugs to slow heart rate—amiodarone, beta
blockers, digoxin, verapamil, diltiazem
• Adenosine, Corvert, verapamil or diltiazem may
be used to convert PSVT to NSR.
Principles of Treatment—Ventricular
Dysrhythmias
• Beta blocker may be first line
• Amiodarone (IV/PO), Tambocor (PO), Rythmol
(PO) and Betapace (PO)are indicated in lifethreatening ventricular dysrhythmias
• Lidocaine may be used in clients with
structurally normal hearts. Also in digoxin
induced ventricular dysrhythmias.