Download Key issues in Chronic Heart Failure Chronic Heart Failure (CHF)

CONTEMPORARY STANDARDS IN
TREATMENT OF CHRONIC HEART FAILURE
JERZY JANKOWSKI MD
DEPARTMENT OF CLINICAL PHARMACOLOGY
http://www.zfk.ump.edu.pl/
Key issues in Chronic Heart Failure
Chronic Heart Failure (CHF) is
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Common- 2% of the population
Dangerous- high mortality
Disabling- high morbidity
Costly- 2% of health care budget
Treatable- very successful pharmocological
therapy developed
Definition of CHF
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Heart failure (HF) is the inability of the heart to maintain an
output adequate to meet the metabolic demands of the body.
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Definition of HF
I. Symptoms and signs of heart failure (at rest or during exercise)
and
II. Objective evidence (preferably by echocardiography) of
Cardiac dysfunction (systolicand/ordiastolic) (at rest) and (in cases where
the diagnosis is in doubt)
and
III. Response to treatment directed towards heart failure
*Criteria I and II should be fulfiled in all cases.
Pathophysiology of Heart Failure
Autonomic and hormonal control of cardiovascular function
Pathophysiology of Heart Failure
Pathophysiology of Cardiac Performance
Cardiac performance is a function of 4 factors
PRELOAD
AFTERLOAD
CONTRACTILITY
HEART RATE
Preload
Diuretics in Heart Failure
Loop diuretics: furosemide, torsemide
Thiazide and thiazide-like diuretics:
hydrochlorothiazide
chlorthalidone
K+ sparing diuretics:
Na+ channel inhibitors: amiloride, triamterene
Aldosteron antagonists: spironolactone,eplerenone
Diuretics in Heart Failure
Loop Diuretics
Furosemide, torsemide, ethacrinic acide, torsemide
Secreted into the tubular fluid by proximal tubule cells
Loop Diuretics: Side Effects and Drug
Interaction
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Volume depletion, hyponatremia, hypokalemia
Hypocalcemia, hypomagnesemia, hypochloremia
Ototoxicity – especially with ethacrynic acid
Hypotension
Metabolic effects – hyperuricemia, hyperglycemia,
hypercholesterolemia (↑LDL, ↓HDL, ↑TGL)
Cardiac glycosides (risk of ventricular arrhythmias)
Aminoglycoside antibiotics, cisplatin (risk of ototoxicity)
Loop Diuretics: Drug Interaction
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NSAIDs – reduced effects
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Probenecid – blocks secretion into the distal
tubule and decreases the response to the LD
Thiazide Diuretics
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Hydrochlorothiazide – the prototype for this
class of drugs
Thiazide-like – chlorthalidone, indapamide and
metolazone (long acting diuretics)
The same mechanism of action
Thiazide Diuretics – Side Effects
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Electrolyte abnormalities – hypokaliemia,
hyponatremia, hypercalcemia, hypomagnesemia,
hypochloremia, hypovolemia
Hyperuricemia, hyperglycemia (reduced effecacy
of hypoglycemic drugs
Increased plasma levels of LDL and TGL
Sexual dysfunction
Cardiac arrhythmias
Drug interactions – as loop diuretics
Aldosterone Antagonists
Aldosterone Antagonists
Aldosterone Antagonists
Aldosterone Antagonists
RALES TRIAL
RALES TRIAL
Aldosterone Antagonists
EPHESUS TRIAL
EPHESUS TRIAL
EPHESUS TRIAL
EPHESUS TRIAL
EPHESUS TRIAL
EPHESUS TRIAL
Cardiac glycosides
Cardiac glycosides – mechanism of action
Pharmacokinetics (Digoxin, Digitoxin)
Highly variable kinetics + VERY narrow
therapeutic index = need to individualize dose
regiments
Relatively long half-lives of elimination
accumulation to stedy state
loading doses employed
delays following changes in therapy
Pharmacokinetics
Plasma concentration determinations
Effective range = 1.0 – 2.5 ng/ml
Toxic range
= 1.5 – and up
Rarely essential to a diagnosis of toxicity
Estimate of degree of overdose
Can be used to calculate dose adjustments
Comparative Pharmacokinetics
Toxicity
Gastrointestinal (relate to vagal effects)
anorexia
abdominal discomfort
vomiting
diarrhea
Toxicity
Cardiac disturbances
premature ventricular depolarization
nodal rhytms
A – V dissociation
Treatment of Toxicity
• Stop giving the drug (for a time)
• Potassium (if hypokalemic)
• Cholstyramine, activated charcoal
(to bind
digoxin in GI tract and shorten half-life )
• Digoxin Antibodies (Fab fragments)
• Antiarrhythmics (very cautiously)
• Electrotherapy (defibrillation only in the
case of VF
Drug Interactions
• Increased plasma concentration – verapamil,
diltiazem, quinidine, amiodaron, spironolacton
• Changes in plasma electrolyte – diuretics, salts
(K+, Ca++), adrenocorticoids
• Changes in digoxin absorption – antacids,
cholestyramine, laxatives, antidiarrheal
absorbents
• Changes in cardiac cell activity sympathomimetics