Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
OVERVIEW
HEART FAILURE:
Complex, progressive disorder in which the
heart is unable to pump sufficient blood to
meet the needs of the body
manifestations:
Dyspnea
Fatigue
Fluid retention
Impaired ability of the heart to adequately
fill with and/or eject blood
Causes:
Arteriosclerotic heart disease
Myocardial infarction
Hypertensive heart disease
Valvular heart disease
Dilated cardiomyopathy
Congenital heart disease
Left systolic dysfunction secondary to CAD
Most common cause of HF
70% of cases
6 classes of drugs
Renin-angiotensin inhibitors
B-adrenoceptor blockers
Diuretics
Direct vasodilators
Inotropic agents
Aldosterone antagonists
Can use 1 or more of these drugs depending
on the severity of HF
Inc
Inc venous Sympathetic Inc RA
pressure activity II
Inc
Aldosterone
Inc
capillary
filtration
Inc Na+ and
EDEMA H20 retention
1. Increase sympathetic activity
baroreceptors ( sense a decrease in BP)
Attempt to sustain tissue perfusion
- adrenergic receptors
Increase HR
Increase force of contraction
1 stimulation
Vasoconstriction
Enhance venous return
Increase cardiac preload
Peripheral edema
Pulmonary edema
3. Myocardial hypertrophy
Increase in size and chambers dilate and become
more globular
Initially stretches the muscle stronger
contraction
Excessive elongation weak contraction
diminishes the ability to eject blood systolic HF
NSAIDS
alcohol
CCB
High dose -blockers
Antiarrhythmic drugs
DRUGS USED IN HEART
FAILURE
ANGIOTENSIN-
RECEPTOR
ACE INHIBITORS BLOCKERS
Candesartan
Captopril
Losartan
Enalapril
Fosinopril Telmisartan
Lisinopril Valsartan
Quinapril
Ramipril
DRUGS USED IN HEART
FAILURE
BETA
ADRENOCEPTOR DIURETICS
BLOCKERS
Bumetanide
Furosemide
Atenolol Hydrochlorothiazide
Carvedilol Metolazone
Metoprolol
DRUGS USED IN HEART
FAILURE
DIRECT
VASODILATORS INOTROPICS
Digoxin
Hydralazine Dobutamine
Isosorbide dinitrate
Inamrinone (amrinon)
Isosorbide mononitrate
Sodium nitroprusside Milrinone
DRUGS USED IN HEART
FAILURE
ALDOSTERONE ANTAGONISTS
Eplerenone
Spironolactone
INHIBITORS OF RENIN-ANGIOTENSIN
SYSTEM
HEART FAILURE activate RAS via 2
mechanisms
Increase renin release by JG cells in afferent
arterioles in response to diminished renal
perfusion pressure
Renin release is promoted by sympathetic
stimulation and activation of receptors
Increase
Decrease vasodilation of
Angiotensin angiotensin
I vascular smooth
II
muscle
Decrease
retention of
ACE
sodium and water
inhibitor
s
Time
Indications:
Maybe considered as single agent with mild
dyspnea on exertion and do not show S/S of
volume overload (edema)
Used in all stages of Left ventricular failure
Greatest benefits in those with lowest EF
Beneficial to post MI (long term use)
Recommended to be initiated immediately in
patients with MI
Maybe used in combination with diuretics,
blockers, digoxin and aldosterone antagonists
(dependent on the disease severity)
ACE INHIBITORS
KINETICS
Adequately but incompletely absorbed following
oral administration
Presence of food decreases its absorption
Pro-drugs that require activation by hydrolysis
via hepatic enzymes except CAPTOPRIL
Once daily
Ramipril
Fosinopril
Adverse effects:
Postural hypotension
Real insufficiency
Hyperkalemia
Angioedema
Persistent dry cough
Not used in pregnant women toxic to fetus
ANGIOTENSIN RECEPTOR BLOCKERS
Nonpeptide, orally active compounds
Extremely potent competitive antagonists of
the angiotensin type I receptor
Pharmacokinetics:
All are orally active and require once a day
dosing
Losartan first approved member and it
undergoes extensive first-pass hepatic
metabolism including its conversion to active
metabolite
Elimination of metabolites and parent
compound
Urine and feces
Adverse effects:
Similar to ACE inhibitors
Contraindicated in pregnancy
BLOCKERS
Negative inotropic effect
Improve systolic function and reverse cardiac
remodeling
Loop diuretics;
Used in patients who require extensive diuresis
and those with renal insufficiency
Most commonly used in HF
Overdose profound hypovolemia
DIRECT VASODILATORS
Dilation of venous vesselsdecrease cardiac
preload due to increase venous capacitance
Ex: nitrates
free Ca++
Increase contractility of the cardiac muscle CO
closely resemble that of the normal heart
half-life(days)
0 50 100
Digoxin
Very potent
Narrow margin of safety
Long half life (36 hours)
Mainly eliminated in the kidneys
Large Vd (accumulates in muscles)
Dose depends on lean body weight
Digitalization if needed
Digitoxin
Much longer half life
Extensively metabolized by liver before
excreted in feces
Adverse effects
GI effects:
Anorexia, nausea/vomiting
CNS effects:
Headache, fatigue, confusion, blurred vision,
alteration of color perception, halos on dark
objects
Factors that predispose to digoxin toxicity
Electrolyte disturbances
hypokalemia ( loop or thiazide diuretics)
Hypercalcemia
Hypomagnesemia
drugs
Displace digoxin from
quininide
tissue-protein binding site
Verapamil
Compete with digoxin for
amiodarone
renal excretion
Enhance
potential
cardiotoxicity
Corticosteroid
Thiazide
Decrease diuretics
K+ levels Loop diuretics
Other that predispose digoxin
toxicity
Hypothyroidism
Hypoxia
Renal failure
myocarditis
Beta adrenergic agonists
(+) inotropic effect and vasodilation
Dobutamine primarily used as inotropic agent in
hospital settings
Phosphodiesterase inhibitors
Inamrinone( formerly amrinone) and Milrinone
Increase intracellullar Ca++
Long term therapy increase risk of mortality
Short term not associated and sometimes
beneficial in refractory HF
ALDOSTERONE ANTAGONISTS
Advance heart disease elevated levels of
aldosterone due to angiotensin II stimulation
and reduce hepatic clearance
1. Spironolactone
Direct antagonist of aldosterone (salt retension,
hypertrophy and hypokalemia)
Reserve for most advance cases of HF
Adverse effects:
Gastric gastritis and peptic ulcer
CNS lethargy and confusion
Endocrine gynecomastia, dec libido, menstrual
irregularities
2. Eplerenone
competitive antagonists of aldosterone at
mineralocortcoid receptors
Lower incidence of endocrine related side
effects
Low affinity for glucocorticoids, androgen and
progesterone receptors