Inotropic Agents I and II Flashcards
How is CHF defined?
inability of the heart to pump blood at a rate commensurate with the requirements of the tissues
How is heart failure defined?
any structural or functional disorder that impairs the ability of the ventricle to fill with or eject blood
What are the clinical manifestations of heart failure?
dyspnea
fatigue
fluid retention (CONGESTIVE)
Does the ventricle size and function have to be abnormal?
no
According to the New York Heart Associations Functional Classifications, how is the following patient classified:
Patient is diagnosed with cardiac disease but it has no impairment in their life.
Class I
According to the New York Heart Associations Functional Classifications, how is the following patient classified:
A patient with cardiac disease who has been running 5 miles a day for 20 years can now only run 3-4 miles at the most before becoming exhausted and short of breath, but they have no symptoms at rest.
Class II
According to the New York Heart Associations Functional Classifications, how is the following patient classified:
A patient with cardiac disease who has been running 5 miles a day for 20 years and is now fatigued and out of breath walking to his mailbox and back, but they have no symptoms at rest.
Class III
According to the New York Heart Associations Functional Classifications, how is the following patient classified:
A patient with cardiac disease who is constantly fatigued and short of breath by walking around their house and has similar symptoms even while he is resting.
Class IV
There is a poor correlation between cardiac function and….
symptoms
Name some noncardiac factors that affect exercise tolerance.
- peripheral vascular fxn
- skeletal muscle physiology
- pulmonary dynamics
- neurohormonal and reflex autonomics
- renal Na handling
How does LV dysfunction usually begin?
with injury to myocardium (usually progresses by change in geometry and structure)
Which hormones and neurotransmitters are elevated in patients with heart failure?
Norepi Angiotensin II Aldosterone Endothelin Vasopressin Cytokines
What are the compensatory mechanisms of the heart in heart failure?
increased HR, contractile stimulation and rate of relaxation
What are the compensatory mechanisms of the peripheral circulation in heart failure?
arterial vasoconstriction (increased afterload) venous vasoconstriction (increased preload)
What are the compensatory mechanisms of the kidney in heart failure?
arterial vasoconstriction
venous vasoconstriction
Na and water retention
increased myocardial contractile stimulation
What are the compensatory mechanisms of oxygen delivery in heart failure?
- redistribution of cardiac output
- altered O2 Hgb dissociation
- increased O2 extraction by tissues
Which two stages are at risk for heart failure and how are they differentiated?
- Stage A and B
- B has structural heart disease, A does not
Which two stages are in heart failure and how are they differentiated?
- Stage C and D
- D has refractory symptoms of HF at rest
How are patients in Stage A treated?
- reduce risk factors
- ACEI or ARD
How are patients in Stage B treated?
Stage A + ACEI, ARB or Beta blockers
How are patients in Stage C treated?
Stage B+
- Diuretics
- ACEI
- Beta Blockers
- Aldo Antagonist
- ARB
- digitalis
- nitrates
- pacemaker
- defibrillators
How are patients in Stage D treated?
Stage C+
- end of life care
- transplant
- chronic inotropes
- mechanical support
- experimental surgery or drugs
What is the first line therapy for heart failure?
ACEI’s
-alleviate symptoms, improve clinical status and reduce risk of death and hospitalization
What are the physiological effects of ACEI’s?
- arteriovenous vasodilation (decrease SVR, BP, PCWP, and LVEDP, increases CO and exercise tolerance)
- no change in HR or contractility
- decreased O2 requirements
- Increased renal, coronary and cerebral blood flow
- diuresis and naturesis
What are the advantages of ACEI’s?
- Inhibit LV remodeling after MI
- modify the progression of chronic CHF
- No neurohormonal activation or reflex tachy
- no tolerance
what is one benefit of the ARB’s over the ACEI’s?
no side effect of cough
How do ARB’s work?
block type 1 angiotensin II:
- dilate arteries and veins
- inhib angiotensin II effect on sympathetic tone
- promotes renal excretion of Na and water
- inhibits cardiac and vascular remodeling
When would using an ACEI and an ARB be indicated?
in patients with resistant hypertension
When there is a side effect of ____________ with and ACEI, adding an ARB is contraindicated.
angioedema-crossover effect
Name the 6 ARB drugs.
- Losartan
- Irbesartan
- Valsartan
- Candesartan
- Olmesartan
- Telmisartan
What are some side effects of the ARB’s?
- decreases GFR
- Increases K+
- Hypotension
What are the effects of the diuretics?
- decrease in volume and preload
- improves arterial distensibility
- neurohormonal activation (increases NE and angiotensin II)
Do diuretics have a direct effect on CO?
NO-but excessive preload reduction can cause decreased CO
What is a contraindication for use of diuretics?
hypovolemia
What are some side effects of diuretics?
- volume contraction
- electrolyte depletion
Name the two aldosterone antagonists for treatment of heart failure
spironolactone and eplerenone
What are some side effects of the aldosterone antagonists? (spironolactone and eplerenone)
- hyperkalemia
- metabolic acidosis
- gynecomastia
- gastric disturbances
How do Beta blockers work in the setting of Heart Failure?
inhibit the adverse effects of the SNS
Which 3 beta blockers have demonstrated a reduction in the risk of death and hospitalization?
- Bisoprolol
- Metoprolol
- Carvediol
How should beta blockers be dosed in heart failure?
- start at very low dose
- gradually increase dose
What class of drugs is digoxin and what was it initially prescribed for?
- cardiac glycosides
- lower extremity edema
What is the mechanism of action of the cardiac glycosides (digoxin)?
inhibits Na/K ATPase–>increase in intracellular Na–>increase in Ca concentration through the Na/Ca exchanger–>increased contractility
What is the mechanism of the decreased sinoatrial firing rate and reduced conduction velocity through the AV node with digoxin treatment?
-increase in vagal efferent activity to the heart
How does Digoxin affect:
- Cardiac Output
- LVEF
- LVEDP
- Exercise Tolerance
- Natriuresis
- Neurohormonal activation
- Cardiac Output- increased
- LVEF- increased
- LVEDP- decreased
- Exercise Tolerance- increased
- Natriuresis- increased
- Neurohormonal activation- decreased
What are the specific neurohormonal effects that are decreased with digoxin?
- Plasma NE
- Peripheral NS activity
- RAAS activity
What is the major drug management issue with digoxin?
-narrow therapeutic window
What does digoxin toxicity cause?
cardiac arrhythmias-atrial tachycardia and AV block
Also eliminated by the kidneys
List the 7 medications/classes of medications that are used to treat heart failure.
- Diuretics
- Digoxin
- Inotropes
- Nitrates
- ACE-I (ARB’s)
- B-Blockers
- Aldosterone antagonists
Which of the following produces decreased mortality in HF patients?
- Diuretics
- Digoxin
- Inotropes
- Nitrates
- ACE-I (ARB’s)
- B-Blockers
- Aldosterone antagonists
- Nitrates
- ACE-I (ARB’s)
- B-Blockers
- Aldosterone antagonists
What is mechanism of action of Dobutamine and what is its result?
- stimulates B-1 receptors on heart
- increased contractility and heart rate
What is the effect of Dobutamine on the blood vessels at low doses? high doses?
- low doses- stim. B-2 receptors causing vasodilation
- high doses- stim alpha receptors causing vasoconstriction
<p>
| What is the half life of Dobutamine and when can tolerance begin to develop?</p>
<p>
| -half life is 2 minutes-->given as continuous infusion -tolerance after 24-48 hours at same dose</p>
What is the mechanism of action of Milrinone?
phosphodiesterase IIIa inhibitor-normally breaks down cAMP so this causes an increase in cAMP–>increased contractility, heart rate, and relaxation of vascular smooth muscle
What is milrinone usually used for?
As a last resort for short term infusions because there is increased hypotensive and atrial arrhythmia events acutely and 2 month mortality is 50% higher than placebo
What is Dobutamine usually used for?
Acutely decompensated patients (about half will die after 6 months)
What is Nesiritide?
recombinant human B-natriuretic peptide which causes natriuresis and diuresis by decreasing:
- Aldosterone
- Cortisol
- Na appetite
- *and increases GFR**
What have studies recently shown regarding the efficacy of nesiritide?
- no difference in rates of death of hospitalization
- no significant improvement of symptoms
Which of the following exhibits neurohormonal control?
- Diuretics
- Digoxin
- Inotropes
- Nitrates
- ACE-I (ARB’s)
- B-Blockers
- Aldosterone antagonists
- Digoxin
- ACE-I (ARB’s)
- B-Blockers
- Aldosterone antagonists
