2. COMPREHENSIVE QUESTION
• A 69-year-old male with a past medical history of congestive heart failure,
type II diabetes mellitus, hypertension, and coronary artery disease presents
for follow-up. Patient has had several MIs, a depressed ejection fraction (EF),
and worsening heart failure—symptoms of dyspnea, orthopnea, paroxysmal
nocturnal dyspnea, and edema despite maximal ACE inhibitor, beta blocker,
and diuretic use. Patient’s diabetes is well controlled and he has a normal
renal function. You decide to add digoxin for symptomatic relief.
• What is the effect of digoxin on the normal heart?
• What is the effect of digoxin on the failing heart?
• What neural effects does digoxin have?
• What are the side effects and toxicities of digoxin?
4. DEFINING CONGESTIVE HEART FAILURE
• The onset and progression of clinically evident CHF from left ventricular
(LV) SYSTOLIC DYSFUNCTION follows a pathophysiologic sequence in
response to an initial insult to myocardial infraction.
• Reduction in output leads to CARDIAC REMODELLING
1. ACTIVATION OF RAAS
2. ACTIVATION OF SYMPATHETIC SYSTEM
• perfusion of vital organs by
1. LV Preload
2. Stimulating myocardial contactability
3. arterial tone
5. Contd.
• Acutely these mechanisms sustain
cardiac output by allowing heart to
operate at
Elevated end diastolic volume
Peripheral vasoconstriction
6. FATE OF MECHANISMS
• Compensatory mech over time propagate disease progression .
• Intravascular volume expansion increases diastolic and systolic wall stress
causes pathological LV hypertrophy.
• By increasing LV afterload ,peripheral arterial vasoconstriction also
adversely affects diastolic ventricular wall stress, thereby increasing O2
demand.
• Neurohumoral effects such as NE and angiotensin II are associated with
Myocardial apoptosis
Abnormal myocyte gene expression
Pathological change in extracellular matrix that causes LV
stiffness
7. ACTUAL DEFINITION
Congestive heart failure is the
pathophysiologic state in which the heart is
unable to pump blood at a rate commensurate
with the requirements of metabolizing
tissues, or can do so only from an elevated
filling pressure
12. MECHANISM OF ACTION
• DIURETICS PROMOTE SALT AND WATER EXCRETION
CIRCULATING VOLUME
PRELOAD
• IMPROVE CARDIAC FUNCTION
• DECRESE DYSPNOEA AND ODEMA
• RELIEF OF SYMPTOMS OF CONGESTION
16. CAUSES OF DIURETIC RESISTANCE
• NON COMPLIANCE WITH MEDICAL REGIMEN
• EXCESS Na +
INTAKE
• DECREASED PERFUSION
• NSAID
• 10 𝑅𝐸𝑁𝐴𝐿 𝑃𝐴𝑇𝐻𝑂𝐿𝑂𝐺𝑌
17. COMPREHENSIVE QUESTION
• A 55 Year old man consults a physician because of episodic weakness and
paresthesia. On one occasion he experienced transient paralysis. He
experiences polyuria,polydipsia, vital are 140/100 mmhg with no edema.
• Serum 𝑘+
= 2.1 Meq/L , SCAN SHOWS SMALL ADRENAL MASS.
• What is the pharmacotherapy?
ANS: SPIRONOLACTONE
18. COMPREHENSIVE QUESTION
• A 79 YR old woman with hypertension, D.M.,CAD, rheumatoid arthritis came to
OPD. Her medications were
𝑅𝑥 SPIRONOLACTONE,AMILORIDE,NPHINSULIN,ASPIRIN,PREDNISONE,
KETOROLAC.
• TEMP 𝟑𝟕𝟎
𝑪 . 𝑩𝑷 =
𝟗𝟗
𝟓𝟔
𝒎𝒎𝒉𝒈; Pulse:58/min ;
Respiration = 19/MIN ; ECG shows sinus rhythm & non specific
ST RHYTHM & T ABNORMALITY. 𝑵𝒂+
= 136 MEq/L; 𝑲+
= 5.8 MEq/L ;
HER 𝑲+
was increasing for 6 months . WHAT IS THE APPROPRIATE
MANAGEMENT?
ANS: TO DISCONTINUE AMILORIDE/SPIRONOLACTONE
26. Pharmacology of the Cardiac Glycosides
DEFINITIONS
• Cardiac glycosides:
The cardenolides include digitalis, digoxin, digitoxin, and ouabain. Digoxin is the only
preparation approved in the United States.
• Inotropic: Affecting myocardial contractility.
• Chronotropic: Affecting heart rate.
• Congestive heart failure: A syndrome with multiple causes that may affect either
systole or diastole. Left heart failure leads to pulmonary congestion and reduced
cardiac output and appears in patients with MI, aortic and mitral valve disease, and
hypertension. Right heart failure leads to peripheral edema and ascites and appears in
patients with tricuspid valve disease, cor pulmonale, and prolonged left heart failure.
• The New York Heart Association classification of congestive heart failure includes
class I (mild disease) to class IV (severe disease).
34. A 69-year-old male with a past medical history of congestive heart failure, type
II diabetes mellitus, hypertension, and coronary artery disease presents for
follow-up. Patient has had several MIs, a depressed ejection fraction (EF), and
worsening heart failure—symptoms of dyspnea, orthopnea, paroxysmal
nocturnal dyspnea, and edema despite maximal ACE inhibitor, beta blocker,
and diuretic use. Patient’s diabetes is well controlled and he has a normal renal
function. You decide to add digoxin for symptomatic relief.
• What is the effect of digoxin on the normal heart?
• What is the effect of digoxin on the failing heart?
• What neural effects does digoxin have?
• What are the side effects and toxicities of digoxin?
35. Summary: A 69-year-old man with congestive heart failure, hypertension, and
diabetes mellitus has a markedly low EF and is prescribed digoxin.
• Effect on a normal heart: Increased systemic vascular resistance and
constriction of smooth muscle in veins, which may decrease cardiac output.
• Effect on a failing heart: Increased stroke volume and increased cardiac
output.
• Neural effects: Decreased sympathetic tone and increased vagal activity,
resulting in inhibition of sinoatrial (SA) node and delayed conduction through
atrioventricular (AV) node.
• Side effects and toxicities: Induction of arrhythmias, loss of appetite, nausea,
vomiting, diarrhea, disorientation, generalized fatigue, and visual
disturbances.
40. SYMPATHOMIMETICS
Dopamine. Dopamine is an endogenous catecholamine with only limited utility
in the treatment of most patients with cardiogenic circulatory failure.
The pharmacologic and hemodynamic effects of dopamine are concentration
dependent. Low doses (≤2 μg/kg lean body mass/min) induces cyclic AMP–dependent
vascular smooth muscle vasodilation.
In addition, activation of D2 receptors on sympathetic nerves in the peripheral
circulation at these concentrations also inhibits NE release and reduces α
adrenergic stimulation of vascular smooth muscle, particularly in splanchnic and
renal arterial beds.
Therefore, low- dose dopamine infusion often is used to increase renal blood flow
and thereby maintain an adequate glomerular filtration rate in hospitalized CHF
patients with impaired renal function refractory to diuretics.
Dopamine also exhibits a pro- diuretic effect directly on renal tubular epithelial
cells that contributes to volume reduction
41. DOBUTAMINE : Dobutamine is the β agonist of choice for the
management of CHF patients with systolic dysfunction.
• In the formulation available for clinical use, dobutamine is a
racemic mixture that stimulates both β1 and β2 receptor subtypes.
• In addition, the (–) enantiomer is an agonist for α adrenergic
receptors, whereas the (+) enantiomer is a weak, partial agonist. At
infusion rates that result in a positive inotropic effect in humans,
the β1 adrenergic effect in the myocardium predominates.
• In the vasculature, the α adrenergic agonist effect of the (–)
enantiomer appears to be offset by the (+) enantiomer and
vasodilating effects of β2 receptor stimulation.
• Thus, the principal hemodynamic effect of dobutamine is an
increase in stroke volume from positive inotropy, although β2
receptor activation may cause a decrease in systemic vascular
resistance and, therefore, mean arterial pressure.
42. • Despite increases in cardiac output, there is relatively little chronotropic
effect.
• Continuous dobutamine infusions are typically initiated at 2-3 μg/kg/min
without a loading dose and uptitrated until the desired hemodynamic
response is achieved.
• Pharmacologic tolerance may limit infusion efficacy beyond 4 days, and,
therefore, addition or sub- stitution with a class III PDE inhibitor may be
necessary to maintain adequate circulatory support.
• The major side effects of dobutamine are tachycardia and
supraventricular or ventricular arrhythmias, which may require a
reduction in dosage. Recent β receptor antagonist use is a common cause
of blunted clinical responsiveness to dobutamine.
