Download (4)CCF DRUGS

Dr. Sanjib Das
VI. Cardiac Glycosides and Congestive Heart Failure
 A. Learning objectives
 What are the causes and major hemodynamic effects of
congestive heart failure?
 How does congestive heart failure alter activity of the
sympathetic nervous and renin-angiotensin systems?
 How are the 4 main factors affecting cardiac performance
altered during congestive heart failure?
 1. Digoxin
 Know for digoxin: (a) absorption, (b) distribution, (c)
metabolism, and (d) excretion?
 What is the basic mechanism of action (or sequence
of events) responsible for their positive inotropic
effects?
 What are their major effects on the heart (i.e., on
contractility, conduction, membrane potentials, tissue
electrolytes, vagal tone, and ECG)?
 Digoxin----contd
 Why does its effect on (a) stroke volume, (b) heart rate, (c) cardiac




output, and (d) vascular tone differ in normal versus failing hearts?
What are their vascular, renal, gastrointestinal, and CNS effects?
Mechanisms by which quinidine may affect responsiveness to
digitalis.
Mechanism of beneficial effects of digoxin in treatment of atrial
fibrillation.
Toxic effects and treatment of digoxin overdose.
2. Other positive inotropic drugs
 How does Inamrinone or milrinone increase myocardial contractility?
 What advantages do the bipyridines have over digoxin in the
treatment of congestive heart failure?
 What advantages do the selective ß1-adrenergic agonists have over
digoxin in the treatment of congestive heart failure?
 Rationale for using angiotensin converting enzyme inhibitors in the
treatment of congestive heart failure.
Incidence of Congestive Heart Failure (CHF)
 CHF results when the heart can no longer supply
oxygenated blood adequately to peripheral tissues
during stress or even at rest
 The heart is unable to pump blood at a rate sufficient
to satisfy the needs of the metabolizing tissues
Incidence of Congestive Heart Failure (CHF)
 CHF is primarily a disease of aging: 75% of existing and
new cases occur in individuals over 65 years.
 CHF prevalence increases with age:
• From < 1% at 50-59 years
• Doubling with every decade
• To reach almost 10% by age 80-89
 Among survivors, quality of life is adversely affected by:
• Progressive fatigue,
• Shortness of breath
• Functional disability
 Poor long-term prognosis even with appropriate treatment
• 5-year survival of 38% in men and 57% in women
• 30-50% of CHF patients with severe symptoms die within
one year
 Mortality can be reduced by drug treatment
Two main types of CHF
Type of CHF
“High-output"
“Low-output"
Main causes
Hyperthyroidism
anemia
arteriovenous shunts
thiamine deficiency
(beriberi)
Coronary artery disease
hypertension
myocardial infarction
persistent arrhythmias
rheumatic heart disease
general cardiomyopathy
Heart work
conditions
Healthy heart exhausted
by working too hard
Heart unable to pump
enough blood to meet
tissue needs
Cardiac output
High as the heart works
hard to keep up with
greatly increased body
demands
Low because the heart is
unable to keep up with the
tissue metabolic demands
Inotropic drug
response
Poor or none
Good, usually improves
NBME
Pathogenesis
of
Low output CHF
A typical case
 The Problem 70 years old man
 2 months Hx of :
 Progressive dyspnea on exertion
 Past 2 weeks he observed:
 PND + 3 pillow orthopnea
 Swollen feet > a week
 Swelling of his abdomen
 known case of hypertension for 10 years> not compliant
 O/E:









Breathlessness at rest
JVP raised 12 cm
Pulse=110/min
BP= 190/110 mmHg
Apex beat at 6th left intercostal space 2 cm outside the mid-clavicular
line.
Heart sounds= 1st, 2nd, 3rd
Crepitations in both lung bases
Tender Palpable liver 4 cm below costal margin
Peripheral oedema & minimal ascites
 CXR: large heart, opacities in both lung bases
Hemodynamic Characteristics of CHF
[A] Subnormal cardiac
output causing decreased
exercise tolerance with rapid
muscular fatigue, tachycardia,
pulmonary edema, and
cardiomegaly
[B] Myocardial hypertrophy
to maintain cardiac
performance increased
myocardial muscle mass and
muscle wall thickness
[C] Neurohumoral reflex
compensation arises from
increased activity of
sympathetic nerves, and
renin-angiotensin-aldosterone
system
Chronic Congestive Heart Failure
EVOLUTION OF
CLINICAL STAGES
NORMAL
Asymptomatic
LV Dysfunction
No symptoms
Compensated
Normal exercise
CHF
Abnormal LV fxn
No symptoms
Decompensated
Exercise
CHF
Abnormal LV fxn
Symptoms
Refractory
Exercise
CHF
Abnormal LV fxn
No symptoms
Normal exercise
Normal LV fxn
Symptoms not controlled
with treatment
Vicious Spiral of Progression of Heart
Failure
Decreased cardiac output (CO) activates production of neurohormones (NE,
norepinephrine; AII, angiotensin II; ET, endothelin), which cause vasoconstriction and
increased afterload. This further reduces ejection fraction (EF) and CO, and the cycle
repeats. The downward spiral is continued until a new steady state is reached in which
CO is lower and afterload is higher than is optimal for normal activity.
Circled points 1, 2, and B represent points on the ventricular function curves depicted
On next slide.
Relation of Left Ventricular (LV)
Performance to Filling Pressure
PATHOPHYSIOLOGY OF CARDIAC PERFORMANCE
DETERMINANTS OF
VENTRICULAR FUNCTION
CONTRACTILITY
PRELOAD
AFTERLOAD
STROKE
VOLUME
- Synergistic LV contraction
- LV wall integrity
- Valvular competence
CARDIAC OUTPUT
HEART
RATE
Main determinants of cardiac workload
I. Preload: forces acting on venous side to affect
myocardial contractility
-As venous return increases  More blood enters the
heart  Intraventricular pressure rises 
Ventricular muscle stretched  Force of
contraction increases
-In CHF preload is elevated by: increases in blood
volume and venous tone



Treatment with venodilator drugs
reduces preload by dilating peripheral
veins to retain more blood and keep
blood away from the heart
Treatment with diuretics reduces
preload by decreasing blood volume
Salt restriction
II. Afterload: arterial resistance against which the
heart pumps blood is determined by aortic
impedance and vascular resistance
-In CHF afterload rises because of increases in
sympathetic and renin-angiotensin activity which
elevate peripheral resistance via arterial
constriction
-Treatment with arteriodilator drugs reduces
afterload by decreasing peripheral resistance
Main determinants of cardiac workload
III. Myocardial contractility: inherent ability of cardiac muscles to shorten
and develop force for pumping; contractility is reduced when
myocardial muscle fibers do not function properly or become fewer as
in myocardial infarction
 In CHF contractility is reduced because myocardial muscle fibers
are stretched beyond their elastic limits as ventricles become
dilated
 Contractility is increased by inotropic drugs but reduced by badrenergic blockers
IV. Heart rate: determines cardiac output (i.e., CO = HR X SV)
 In CHF reflex tachycardia results from sympathetic overactivity due
to baroreflex activation brought about by the reduction in cardiac
output
 b-adrenergic blocking
drugs reduce cardiac work by
slowing the heart rate
Goals of drug treatment during CHF
CHF Effects
GOAL OF
THERAPY
Increased preload due to:
increased blood volume
increased venous tone
Reduce preload
(unloading)
Increased afterload due to:
increased aortic impedance
increased arterial constriction
Reduce afterload
(unloading)
Arteriodilator
Decreased contractility due
Increase
Inotropic drug
to ventricular dilation
contractility
Reflex tachycardia
Reduce energy
expenditure
NBME
Drugs Used
Diuretic
Venodilator
ß-adrenergic
antagonist
A
C
E/
A
R
B
B. Drugs to be considered
 Inotropes – digoxin (1), inamrinone (2), dobutamine (3)
,dopamine (4)
 Diuretics – hydrochlorothiazide , furosemide (5) , amiloride,
spironolactone
 ACE inhibitors –
captopril (6) & other drugs with common ending with ‘pril’
 AII receptor blockers –
losartan (7) & other with common ending with ‘sartan’.
 Sympatholytics – propranolol, carvedilol (8),metoprolol (9)
 Vasodilators – glyceryl trinitrate (10), hydralazine (11), sodium
nitroprusside (12)
“Cornerstones” of CHF Drug Therapy
ACE inhibitors and other vasodilators to
reduce cardiac workload
I.
II. Diuretics to reduce preload by correcting salt and
water retention

Loop diuretics preferred because of their potency
III. Digoxin to improve cardiac pumping and output

Because of potential digoxin toxicity, a reasonable
therapeutic approach is to start treatment using an
ACE inhibitor alone and if the response is inadequate
then add a loop diuretic and finally digoxin if needed.
ACE Inhibitors in CHF
 ACE inhibitors will counteract the increased renin-angiotensin system (RAS)
activity that occurs during CHF
 Factors that increase RAS activity in CHF include:
(A) Reduced renal perfusion activating renal baroreceptors
NBME
(B) Increased sympathetic activity stimulating ß1-adrenergic receptors on the
JG apparatus
(C) Antihypertensive drugs that stimulate renin secretion:


Diuretics by decreasing delivery of Na+ to the macula densa
Vasodilators by reducing renal perfusion pressure
 Drugs that specifically counteract the increased RAS activity are ACE inhibitors
and angiotensin II antagonists which diminish cardiac workload by:
• Decreasing afterload - reduce angiotensin-vasoconstriction
• Decreasing preload - reduce aldosterone release and fluid volume
 Effective ACE inhibitors include: captopril, enalapril, lisinopril, ramipril, and
quinapril
 Chronic ACE inhibitor therapy can reduce CHF mortality by 28-40%
 Angiotensin (AT1) antagonists act through the same mechanisms and may also
prove as effective for CHF treatment
Angiotensin Receptor Antagonists
 Candesartan, eprosartan, irvesartan, losartan, olmisartan, telmisartan, or
valsartan
 Two types of angiotensin II receptors are: AT1 and AT2
• AT1 receptors predominate in vascular smooth muscle and cause most of
the known actions of angiotensin II
• All currently available AT II antagonists act by selectively blocking AT1
without affecting AT2 receptors
NBME
 Two important differences from ACE inhibitors:
[1] More specific than ACE inhibitors because AT II antagonists do not
affect bradykinin metabolism they do not cause coughing or angioneurotic
edema), and
[2] More complete inhibition of angiotensin action because enzymes
other than ACE than can generate angiotensin II (i.e., ACE inhibitors will
only reduce angiotensin II formation by ACE while AT II antagonists will
block all angiotensin effects regardless of how angiotensin is formed, not
only through ACE but also through other enzymes)
 Except for the absence of coughing or angioneurotic edema, adverse effects
are like those produced by ACE inhibition including: hyperkalemia and
reduced renal function
NBME
Other Vasodilators for CHF

Sodium nitroprusside is infused intravenously in acute decompensated
CHF as long as cerebral and renal perfusion can be maintained despite
the reduction in systemic BP




It is a balanced vasodilator that dilates both veins and arteries to reduce
both preload and afterload
The most common adverse effect is excessive hypotension
Organic nitrates like nitroglycerin or isosorbide dinitrate given orally
dilate veins more than arteries thus lowering preload more than afterload;
however, tolerance precludes their long-term use
Calcium-channel antagonists (CCA) like nifedipine block
slow calcium channels to reduce intracellular calcium, relax
arteriolar smooth muscles, and produce vasodilation
•
•
•
By contrast, verapamil and diltiazem inhibit cardiac contraction, SA
node impulse generation, and AV node conduction
Verapamil and diltiazem should not be used for treatment of CHF
because their cardiac effects may worsen CHF symptoms and increase
mortality
Dihydropyridines markedly enhance periperal edema which worsens
CHF

Amlodipine not as bad as others, but still should be stopped as CHF
progresses
ß-adrenergic antagonists for CHF
 b-adrenergic blockers produce a negative inotropic effect which could
worsen ventricular function and be potentially harmful in CHF
NBME
• Despite this, many clinical studies show that long-term treatment with
b-adrenergic blockers improves symptoms of CHF by slowing heart
rate and contraction velocity to improve:
 Cardiac output
 Exercise tolerance
 Ventricular function
• Exact mechanisms to explain the beneficial effects of b-adrenergic
blockade remain uncertain but may include:
 Decreased heart rate and cardiac work
 Attenuation of responses to high catecholamine concentrations
 Up-regulation of b-adrenergic receptors
 Reduced myocardial remodeling
• Those shown to be effective include:
 Bisoprolol
 Metoprolol
 Carvedilol
DIURETICS in CHF
 Diuretics act to reduce extracellular fluid volume and
thereby reduce preload
 Chronic diuretic treatment is used only for CHF patients with
advanced disease and symptoms
 First-choice drugs are loop diuretics furosemide,
NBME
bumetanide, and torsemide; reserve ethacrynic acid only
for patients allergic to sulfonamides
 Thiazides are weaker diuretics used only for mild CHF
 Concurrent treatment with any vasodilator may reduce renal
blood flow and thus inhibit diuretic efficacy
INOTROPIC DRUGS: Digoxin
 Originally obtained from digitalis (foxglove) plants or toad
skin (protective venom)
 Previous uses included:
• Diuretic and rat poison by ancient Romans
• Arrow poison by some African tribes
• Draft evaders during WW II to simulate heart disease
 Are therefore potentially toxic so beware of digitalis toxicity!
 Until the late 90’s digitalis was among most commonly
prescribed drugs in the US and given to 17-27% of all
hospital admissions
 Digoxin, the only glycoside now used in th US, is used
mainly for treatment of CHF and of atrial fibrillation
INOTROPIC DRUGS: Digoxin
 Chemical structure of digoxin has two parts:
• Aglycone or genin is responsible for all biological activity
• 3 molecules of sugar (digitoxose) influence pharmacokinetics including
absorption, half-life, and metabolism
 Two other digitalis glycosides that are still referred to are:
• Digitoxin - no longer available in the US
• Ouabain - used experimentally
DIGOXIN: Cardiac Effects
 Most important cardiac effects are mechanical and
electrophysiological
 Mechanical effects are on:
• Myocardial contractility (stroke volume) is always increased in both
normal and failing hearts; also known as positive inotropy which is
most important for treatment of CHF
• Mechanism of inotropic action begins with:






Inhibition of Na+/K+ATPase (aka: digitalis receptor) 
Intracellular increase in Na+ and decrease in K+ 
Decreased expulsion of intracellular Ca2+ 
Increased intracellular Ca2+ 
Increased actin-myosin interaction by intracellular Ca2+ 
Increased force of myocardial contraction
DIGOXIN Inotropic Effect
1) Digoxin inhibits
Na+/K+ATPase to
decrease extrusion of
Na+ and increase it
intracellularly
2) Increased
intracellular Na+
inhibits the Na+/Ca2+
exchanger to decrease
extrusion of Ca2+ and
increase it
intracellularly
3) Trigger Ca2+ taken
SR followed by large
Ca2+ release
4) More Ca2+ is released
via the ryanodine
receptor (RyR) and
available to increase
contraction
DIGOXIN: Cardiac Effects
 Because potassium and digoxin inhibit each others binding to Na+/K+ATPase
receptor, potassium counteracts digoxin toxicity and reduces abnormal
cardiac automaticity
 By contrast, calcium increases digoxin toxicity
 Digoxin toxicity should therefore be treated with potassium but never, never with
calcium
 Heart rate is decreased
• In failing hearts bradycardia is due to decreased sympathetic tone
• In untreated CHF sympathetic activity is already high but upon treatment with
digoxin, contractility and cardiac output will be increased thus removing the
stimulus for the increased sympathetic tone
 Cardiac output increased by digoxin in CHF because of the increased
contractility
• Increased cardiac output will remove the stimulus for sympathetic overactivity so
that the ensuing reduction in sympathetic tone will cause:


Venodilation = reduced preload
Arteriodilation = reduced afterload
 Hence, cardiac output improves not only because of direct cardiac
stimulation but also because of venous and arterial dilation due to decreased
sympathetic tone
DIGOXIN: Cardiac Effects
NBME
 Electrical effects result from two actions that are dose-dependent:
• Direct action on myocardial cells (↓ of Na+/K+ATPase → Na+/Ca+
entrapment inside cell→ Tachyarrhythmogenic activity
• Indirect action by parasympathetic stimulation (due to ↓ of Na+/K+ATPase
of Neuronal cells→nodal tissue depolarization→ ↓ SA & AV nodal activity→
Bradyarrhythmic activity)
• Indirect action of sympathetic stimulation (due to ↓ of Na+/K+ATPase of
Neuronal cells→only ventricular tissue depolarization→ Tachyarrhythmogenic
activity)
 Therapeutic doses decrease automaticity, prolong refractory period, and
slow AV node conduction
 In failing hearts digoxin produces bradycardia by decreasing sympathetic tone
• By increasing contractility, digoxin will increase cardiac output and thereby
remove the stimulus for the elevated sympathetic tone in CHF
 Toxic doses can cause arrhythmias by increasing sympathetic activity and
automaticity to form ectopic foci
• Slowed conduction may cause sinus bradycardia or heart block
• May produce almost every variety of arrhythmia
 Based on the reduction in conduction velocity in the AV node digoxin is used for
pretreatment in atrial fibrillation before antiarrhythmic drugs are used
• Antiarrhythmic drugs when given alone may cause paradoxical ventricular
tachycardia which can be prevented by pretreatment digoxin which will slow the
ventricular rate
DIGOXIN: electrophysiological & ECG effects
Site of action
Electrophysiologic
effect
NBME
ECG change
A-V node
Prolonged Refractory
Period 
slowed conduction
Prolonged P-R interval
Ventricle
Accelerated
repolarization
Shortened Q-T interval
Ventricle
Changes in phase 2 or 3, Depressed S-T segment
or in direction of
or inverted T wave
repolarization
DIGOXIN: other effects
 Two opposing vascular effects depending on myocardial
status:
 Normal hearts - contract smooth muscle  vasoconstriction
 Failing hearts - increase cardiac output  remove the stimulus for
sympathetic hyperactivity  reduced sympathetic activity 
vasodilation
 Kidneys are affected only slightly, if at all; diuresis results from
hemodynamic improvement caused by increased cardiac
contractility  increased cardiac output  improved renal
perfusion
• Increased GFR is due to cardiac, rather than renal, actions
• Digoxin causes diuresis only in edematous patients with CHF
• No diuresis in normal subjects or other types of edema
 Gastrointestinal effects include:
• Anorexia and diarrhea due to direct gastrointestinal irritation
• Vomiting due to stimulation of the chemoreceptor trigger zone
• Abdominal pain due to mesenteric arteriolar constriction
DIGOXIN: common adverse effects
NBME
 Narrow margin of safety and toxicity is common because the therapeutic dose is 5060% of the toxic dose and adverse effects often occur even with therapeutic doses;
toxicity leads to discontinuing digoxin in 5-25% of patients
 Earliest signs of intoxication are gastrointestinal (↓ of Na+/K+ATPase )
•
•
•
•
Anorexia, nausea, vomiting, diarrhea, abdominal discomfort
Copious salivation often accompanies the nausea
Vomiting can be harmful as it requires great physical effort
GI symptoms disappear a few days after discontinuing digoxin
 Most dangerous adverse effects are cardiac; can simulate almost all arrhythmias
including sinus bradycardia, ectopic ventricular beats, AV block, and bigeminy
• Cardiac toxicity may be lethal and necessitate stopping therapy
• Most common cause of death is ventricular fibrillation
• Always monitor adverse cardiac effects by routine measurements of ECG, and
serum digoxin and potassium
 CNS adverse effects (↓ of Na+/K+ATPase) include headache, fatigue, malaise,
drowsiness, trigeminal neuralgia, and mental symptoms
• Disorientation and hallucinations often in the elderly
• Color and visual disturbances occur occasionally
 Skin rashes, eosinophilia, and gynecomastia rarely
 Treatment of intoxication should include: discontinue digoxin administration; oral or
intravenous potassium; lidocaine or phenytoin; and digoxin antibodies (digoxin
immune fab)
DIGOXIN: drug interactions
 Many drugs can influence digoxin toxicity and this
is important because treatment of CHF often
requires concurrent administration of digoxin with
diuretics, quinidine, and other antiarrhythmic or
cardiovascular drugs
Pharmacokinetic interactions either:
 Digoxin toxicity enhance by:
 Decreasing digoxin renal clearance or volume of distribution as
with quinidine, amiodarone, captopril, verapamil, diltiazem,
cyclosporine
 Increasing digoxin GI absorption by erythromycin, omeprazole, etc
 Digoxin toxicity reduced by:
 Increasing digoxin renal clearance by thyroxine
 Decreasing digoxin GI absorption by cholestyramine, bran, etc
DIGOXIN: drug interactions
 Many drugs can influence digoxin toxicity and this is important because
treatment of CHF often requires concurrent administration of digoxin
with diuretics, quinidine, and other antiarrhythmic or cardiovascular
drugs
 Pharmacodynamic interactions that enhance toxicity include:
• Kaliuretic diuretics which produce hypokalemia as when digoxin is used
together with thiazide or loop diuretics for treatment of CHF
• b-adrenergic antagonists which inhibit SA or AV node activity
• Calcium-channel antagonists which inhibit contractility
• Catecholamines may sensitize the myocardium to digoxin
NBME
 Hypothyroidism also predisposes to intoxication by reducing renal
clearance to elevate serum digoxin levels
 Elderly patients are more susceptible to digoxin intoxication as their
serum digoxin levels are elevated by hypochlorhydria or reduced renal
clearance; infants usually require larger doses
OTHER INOTROPES: PDE Inhibitors
 Phosphodiesterases (PDE) inactivate cAMP and cGMP, and unspecific PDE
inhibitors like theophylline and aminophylline were once used as heart stimulants
 In the 80’s, specific PDE inhibitors which had inotropic and smooth muscle relaxing
properties were discovered and widely tested but results have been equivocal
 Inamrinone (aka amrinone) and milrinone are given by injection but vesnarinone,
is orally active
 All 3 inhibit type III phosphodiesterase which is present in cardiac and smooth
muscles; they do not affect Na+/K+ATPase or adrenergic receptors
 They increase myocardial contractility by increasing cAMP and inward calcium flux
in the heart
• Also relax vascular smooth muscles to cause vasodilation
 Inamrinone and milrinone in long-term trials often produced intolerable adverse
effects (arrhythmias, liver and bone marrow toxicity), had minimal long-term efficacy,
and increased mortality in CHF patients
 Used only for short-term treatment in advanced heart failure
OTHER INOTROPES: ß-Adrenergic &
Dopaminergic Agonists
 Dopamine and ß1-adrenergic agonists like
dobutamine (Dobutrex) are infused IV to increase
myocardial contractility in acute CHF
 ß2-adrenergic agonists like albuterol or
pirbuterol relax vascular smooth muscles and
have been tested as vasodilators in CHF
 Most of these drugs are ineffective orally and are
currently used only for acute failure or failure
refractory to oral drugs
Extra Credit Quiz
Section
A typical case
 The Problem 70 years old man
 2 months Hx of :
 Progressive dyspnea on exertion
 Past 2 weeks he observed:
 PND + 3 pillow orthopnea
 Swollen feet > a week
 Swelling of his abdomen
 known case of hypertension for 10 years> not compliant
 O/E:









Breathlessness at rest
JVP raised 12 cm
Pulse=110/min
BP= 190/110 mmHg
Apex beat at 6th left intercostal space 2 cm outside the mid-clavicular
line.
Heart sounds= 1st, 2nd, 3rd
Crepitations in both lung bases
Tender Palpable liver 4 cm below costal margin
Peripheral oedema & minimal ascites
 CXR: large heart, opacities in both lung bases
Treatment Objectives
 To relieve symptoms and improve quality of life
 To improve cardiac output
 To treat the precipitating cause
 To treat complications
Non Pharmacological T/t
•
•
•
•
•
•
Reduce salt intake
Reduce weight in overweight and obese individuals
Avoid alcohol
Avoid smoking
Encourage moderate exercise
Bed rest in hospitalised patients
Pharmacological T/t
Initial therapy of mild heart failure (NYHA CLASS I-II)
• Furosemide (frusemide), oral,
Adults
40-80 mg daily
Children
1-2 mg/kg daily
• Lisinopril, oral, (only when blood pressure > 100/60 mmHg)
Adults
2.5-20 mg daily
• Or
• Carvedilol, oral,
Adults
3.125-12.5 mg 12 hourly (maximum 25 mg 12 hourly)
• Or
Pharmacological T/t
• Bisoprolol, oral,
Adults
1.25-10 mg daily
• Initial therapy of moderate heart failure (NYHA CLASS III)
• Furosemide (frusemide), oral,
Adults
80-120 mg daily
Children
2-4 mg/kg daily
• · Lisinopril, oral,
Adults
2.5-20 mg daily
• Or
Pharmacological T/t
• Losartan, oral,
Adults
25-50 mg daily
• Spironolactone, oral,
Adults
25-50 mg daily
• In patients with fast atrial fibrillation
• Digoxin, oral,
Adults
250 micrograms 12 hourly for 24-48 hours,
Then
250 micrograms once daily
Elderly
125 micrograms 12 hourly for 24-48 hours,
Then
Pharmacological T/t
Then
125 micrograms once daily
Children
5 micrograms/kg 12 hourly
Initial therapy of severe heart failure (NYHA CLASS IV)
• Admit patient
• Prop patient up in bed
• Oxygen, by nasal cannula or face mask
• Insert an intravenous cannula
• Furosemide (Frusemide), IV,
40-80 mg, repeat after 30 minutes if necessary;
Thereafter
Pharmacological T/t
• Furosemide (Frusemide), IV,
40-80 mg 12 hourly;
• If patient improves, change to
• Frusemide, oral,
40-80 mg, 12 hourly after 24- 48 hours of IV treatment
• If patient does not improve, continue
• Furosemide (Frusemide), IV, 40-80 mg, 12 hourly and give in
addition
• Morphine, IV,
5-10 mg slowly
And
• Metoclopramide, IV,
• 10 mg to prevent vomiting
Pharmacological T/t
•
•
•
•
•
•
•
•
•
•
•
If there is fast atrial fibrillation,
Digoxin, oral,
250 micrograms 12 hourly for 24-48 hours,
Then
250 micrograms once daily
If there is cardiogenic shock,
Dobutamine, IV,
2.5-10 micrograms/kg/minute
Monitor urine output
Encourage early ambulation
Consider anticoagulation prophylaxis against venous thrombosis,
Enoxaparin, subcutaneously,
40 mg daily
Identify and treat (if possible) precipitating causes such as hypertension,
myocardial infarction, anaemia or thyrotoxicosis
Medicament
Dr._______
Correspondence details
Licence details
Date
Name of the patient
Age,Sex,Occupation
Correspondence details
Rx
------------------------------------------------------------------------------------------------------------------Nonpharmacotherapeutical Intervention
1.
2.
3.
Pharmacotherapeutical Intervention
(S.No) (Dosage form).(Trade/Generic drug name)(dose) (Frequency) (Duration) (special instruction if any)
1.
2.
3.
---------------------------------------------------------------------------------------------------------Instruction to Pharmacist
---------------------------------------------------------------------------------------------------------Signature
Now answer the following Qs.before you start
practicing MCQs
 1. Digoxin
 What is the basic mechanism of action (or sequence of events)






responsible for their positive inotropic effects?
What are their major effects on the heart (i.e., on contractility, conduction,
membrane potentials, tissue electrolytes, vagal tone, and ECG)?
Why does its effect on (a) stroke volume, (b) heart rate, (c) cardiac
output, and (d) vascular tone differ in normal versus failing hearts?
What are their vascular, renal, gastrointestinal, and CNS effects?
Mechanisms by which quinidine may affect responsiveness to digitalis.
Mechanism of beneficial effects of digoxin in treatment of atrial fibrillation.
Toxic effects and treatment of digoxin overdose.
2. Other positive inotropic drugs
 How does Inamrinone or milrinone increase myocardial contractility?
 What advantages do the bipyridines have over digoxin in the treatment of
congestive heart failure?
 What advantages do the selective ß1-adrenergic agonists have over
digoxin in the treatment of congestive heart failure?
 Rationale for using angiotensin converting enzyme inhibitors in the
treatment of congestive heart failure.
In a 65-year-old man who has severe congestive heart
failure with pulmonary edema, treatment with
diuretics or venodilators would be beneficial because
of which of following mechanisms?
A) Decreased myocardial contractility
B) Increased myocardial contractility
C) Reflex tachycardia
D) Reduced afterload
ANS = E
Diuretics and
E) Reduced preload
venodilators
decrease preload
In a 55-year-old man receiving digoxin for treatment
of congestive heart failure, which of the following
would be the earliest sign of digoxin intoxication?
A) Visual disturbances
B) Bigeminy
C) Sinus bradycardia
D) Trigeminal neuralgia
E) Anorexia
ANS = E
GI toxicity occurs the
earliest; Cardiac toxicity
is most life-threatening
Paradoxical benefit of beta blockers
Drugs to be considered for heart failure
Digitalis
Bipyridines
Diuretics
β-adrenergic
agonists
Digoxin
Inamrinone
Milrinone
Thiazide,
Loop, and
Potassiumsparing
Dobutamine
Dopamine (D1)
Na/K ATPase I
PDEI
Digoxin
Force
CO
HR
PR
Normal




CHF




Vasodilators
and ACE
inhibitors
Adverse effects
GI
CNS
Visual
Cardiac
A 65-year-old man with hypertension, managed for several
years with medications, has recently gained about 25
pounds and complains of swollen feet and shortness of
breath. Clinical findings include blood pressure of 170/100
mm Hg, pulse 100 bpm, ankle edema, dyspnea and
cyanosis. Current medications, including
hydrochlorothiazide, atenolol, and naproxen were
discontinued. Which of the following combination of
medications would be most appropriate for treating the
current status of this patient?
A.
B.
C.
D.
E.
Digoxin + quinidine
Digoxin + butoxamine
Enalapril + furosemide
Minoxidil + reserpine
Prazosin + diltiazem
Answer: C
Never give calcium
channel blockers
in CHF
Which of the following drugs may prolong life
in a 65-year-old man with congestive heart
failure in spite of its negative inotropic effect
on cardiac contractility?
A.
B.
C.
D.
E.
Bumetanide
Digoxin
Dobutamine
Enalapril
Metoprolol
Answer: E
Beta blockers pose
some risk in CHF
because of negative
inotropic effect >>>
but overall have positive
outcomes.