EPIDEMIOLOGY:
o Most common cause of hospitalization over 65 years of age.
o Afflicts more than 2 million Americans annually.
o 900,000 hospitalization per year.
o PROGNOSIS: Poor
Untreated, 82% of men die within
...
EPIDEMIOLOGY:
o Most common cause of hospitalization over 65 years of age.
o Afflicts more than 2 million Americans annually.
o 900,000 hospitalization per year.
o PROGNOSIS: Poor
Untreated, 82% of men die within 6 years of onset.
Untreated, 67% of women die within 6 years of onset.
Treated, mortality was reduced to 40%
Causes: Myocardial Infarction, hypertension, coronary artery disease, Hyperthyroidism,
Beriberi, anemia, arteriovenous shunts.
HEMODYNAMIC PROPERTIES: Consequences of CHF
o Subnormal Cardiac Output ------> decreased exercise tolerance, tachycardia,
pulmonary edema, cardiomegaly
o Neurohumoral Reflexes: Reflex tachycardia, increased sympathetics, increased
Renin.
o Myocardial Hypertrophy occurs, to maintain cardiac performance.
Ventricular dilation helps to maintain cardiac output to an extent (due to
Starling's Law), but past a certain point it can no longer help.
o Factors affecting cardiac performance:
Higher preload: due to increased blood volume and venous tone.
Higher afterload: due to hypertension, increased arterial tone.
Lower contractility ------> lower inotropic state
Higher heart rate, due to reflex tachycardia
o Edema: Especially pulmonary edema, but also peripheral. Results from decreased
Cardiac Output, by two mechanisms:
Decreased CO ------> impaired venous return ------> higher capillary
hydrostatic pressure
Decreased CO ------> decreased renal perfusion ------> activate renin
angiotensin system RAS ------> aldosterone causes higher Na+
and fluid
retention.
TREATMENT:
o CARDIAC GLYCOSIDES: See CHF PowerPoint Slides :
o MECHANISM: Inhibit Na+
/K+
-ATPase Pump ------> increased intracellular Na+
in myocardium ------> decreased expulsion of Ca+2 in myocardium ------>
tonically higher levels of intracellular Ca+2 ------> increased myocardial
contractility
o MECHANICAL ACTION on HEART:
Increased myocardial contractility
Bradycardia, due to reduced sympathetics.
Increased Cardiac Output, due to reduced TPR (from reduced
sympathetics) and increased inotropic state.
o ELECTRICAL ACTION on HEART:
Direct Effect on AV Node: Increase risk of heart block
Decrease the rate of rise of Phase-0 depolarization at AV node.
Prolong refractory period at AV-Node
Decrease conduction velocity at AV-Node.
Direct Effect on Purkinje Fibers:
Increase automaticity ------> increased risk of arrhythmias. This
occurs by two mechanisms:
Increase the slope of Phase-4 depolarization.
Elevate the resting membrane potential of the SA-Node, as
a consequence of inhibiting the Na+
/K+
-ATPase
Decrease conduction velocity
Parasympathomimetic Effects: Digitalis increases vagal stimulation, by
three mechanisms:
Baroreceptor Sensitization
Central Vagal Stimulation
Facilitate muscarinic transmission at myocardial cells
Hypokalemia potentiates the cardiotoxic effects of Digitalis, since
digitalis deprives cardiac cells of K+
. This effect of K+
is opposite to the
effect seen with quinidine.
o KIDNEY DIURESIS: Digitalis effect on kidney is indirect -- resulting from
improved cardiac output. If cardiac output does not improve, then there will be no
diuresis.
o ACE INHIBITORS: They have significantly decreased mortality due to CHF.
ACTION: They inhibit the activation of the renin-angiotensin system,
which is hyperactive in CHF, due to increased sympathetics.
They reduce afterload: Reduce circulating levels of AngiotensinII
They reduce preload: Reduce Aldosterone ------> reduce blood
volume.
INDICATIONS: ACE Inhibitors are recommended in the following
patients:
All patients with symptomatic CHF due to LV systolic
dysfunction.
Asymptomatic patients with severe LV systolic dysfunction,
HTN, or valvular regurgitation (aortic incompetence, mitral
regurgitation).
Post-MI patients at risk for complications.
o VASODILATORS:
Sodium Nitroprusside: IV, used to treat acutely decompensated CHF,
where brain and kidney perfusion is compromised.
Hydralazine: It maintains renal blood flow. Used to treat CHF in the
presence of kidney dysfunction.
o LOOP DIURETICS: Goal in this case is to reduce blood volume, not reduce
blood pressure.
o XANTHINES: Theophylline can produce coronary vasodilation and
bronchodilation, both of which can be therapeutic in CHF.
LOOP DIURETICS:
MECHANISM: They inhibit the Na+
/K+
/2Cl-
transporter, essentially shutting down the
counter-current multiplier ------> profuse natriuresis.
INDICATIONS:
o Edema, caused by CHF, cirrhosis, or nephrosis.
o Management of hyponatremia or hypercalcemia. Given in combination with
saline infusion.
o Increase K-
and H+
excretion in patients with distal renal tubular acidosis.
PHARMACOKINETICS:
o Furosemide is secreted by a probenecid-sensitive transport mechanism into
proximal tubule. Thus indomethacin or NSAID's decrease its effectiveness.
o Bioavailability 50-70%. Extensively binds to plasma albumin.
ADVERSE EFFECTS:
o Metabolic effects:
Hyponatremia, hypomagnesemia, metabolic acidosis.
Hypokalemia: can be counteracted with K+
-sparing diuretic, or with
supplemental K+
.
Hypochloremic Alkalosis: Increased delivery of Na+
to distal tubules
------> increased RAS and aldosterone ------> increased secretion of K+
and H+
------> hypokalemic alkalosis.
o Hyperuricemia, hypercholesterolemia
o Ototoxicity, especially in patients with impaired renal function.
THIAZIDE DIURETICS:
MECHANISM: They inhibit Na+
/Cl-
antiport ------> natriuresis.
ADVERSE EFFECTS: Also see thiazides under Anti-HTN
o Metabolic Effects:
Marked hyponatremia.
Hypokalemia and Hypomagnesemia: can be particularly bad in folks
with CHF (taking glycosides), cirrhosis, MI, arrhythmias.
Slight hypercalcemia
Hyperuricemia
INDICATIONS:
o Hypertension
o Kidney stones
o Hypercalcuria
o Diabetes Insipidus
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