Pharm 10-Heart Failure Flashcards by Briana Lieberman

What are some definitions of heart failure?

Inability to effectively return all the blood volume it receives to the critter’s circulation
The heart’s inability to deliver adequate oxygen to the critter’s body to maintain normal function and homeostasis
The heart is unable to effectively provide the critter’s tissues with necessary metabolites and remove metabolic wastes

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What is the symptomatic definition of heart failure?

A mismatch between right and left heart volume outputs

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Cachexia

weakness and wasting of the body due to severe chronic illness.

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Right-Sided Failure vs Left-Sided

Left-sided: Cachexia, backs up in lungs develop cough, can’t deliver to the body

Right-sided: ascites, backs up in the body

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Cardio-centric definition of heart failure

The heart’s impaired ability to adequately fill with and or eject blood; implies dual causation (systolic and diastolic dysfunction)

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What does diastolic failure look like?

Thick heart walls
Decreased ventricular filling
Decreased cardiac output
Patients tend to be “older”

Analogy: clown car is fine but you can’t get much into it

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What does systolic failure look like?

Thin heart walls
Decrease in contractility (weakened heart muscle can’t squeeze well)
Decreased ejection fraction (left side wall is thin and stretched out so trouble pumping); fills ok
Tend to be “younger”

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Batista Procedure

Cut out part of the left ventricle going to renormalize geometry of the heart; great results at first but then very bad

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What are the 5 main causes of heart failure?

Ischemia
Idiopathic
Viral
Immune Mediated
HTN

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What is the most common cause of heart failure?

ischemia; 70% type of HF in America

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Ischemia contributes to which type of heart failure dysfunction?

both systolic and diastolic

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Idiopathic

Unknown cause

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About how common is familial causes in idiopathic heart failure?

1/3

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Describe viral heart failure.

Viruses “errantly” take up residence in myocardial cells; moderate/severe cardiomyopathy, may or may not resolve might require valvular Sx due to new cardiac geometry

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Describe immune-mediated heart failure.

Cardiac antibodies attack cardiomyocytes
Link to other immune-mediate diseases
AMIs expose novel cardiac antigens affecting long-term prognosis

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What forces contribue to the chronic downhill heart failure slide?

Nervous system

2. Renin-angiotensin-aldosterone system

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Why does the heart remodel?

Heart cells die and are replaced with fibrotic tissue and remaining cells hypertrophy

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What are the goals of therapy for HF?

Improve/alleviate critter’s symptoms
Slow that downhill slide toward transplant/VAD/death
Improve survival (increase QALYs)

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6 Classes of QALY-Improving Drugs

Positive inotropes
Diuretics
Renin/Angiotensin Blockers
Primary Vasodilators
B-Blockers
Aldosterone Antagonists
Neprilysin Inhibitor

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What are the 3 types of positive inotropes?

Cardiac Glycosides
Catecholamines
Bypyridines

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What is an example of a cardiac glycoside?

Digitalis (Digoxin)

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Describe the effects of Digitalis (Digoxin).

Positive Inotrope
Negative Chronotrope
Increased Baroreceptor sensitivity

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Describe the therapeutic window of Digitalis (Digoxin)

Narrow therapeutic window (arrythmias, GI symptoms)

no evidence these drugs prolong life

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How does Digitalis (Digoxin) work?

Blocks Na+/K+ -ATPase “The Sodium Pump”

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What are catecholamines?

Classic B-1 adrenergic receptor stimulants | Powerful positive inotropes/chronotropes

What are some examples of catecholamines?

Epinephrine (Adrenaline) norephinephrine (noradrenaline) Dopamine Dobutamine

What is the preferred drug for cardiac arrest?

Epinephrine (Adrenaline)

What are the functions of epinephrine (adrenaline)?

``` Preferred drug for cardiac arrest Anaphylactic reactions (predictable side effects) ```

What is dopamine and what receptors does it act on?

A relatively non-specific catecholamine; acts on dopaminergic receptors

What is dopamine used to treat?

Improves cardiac function in heart failure Renal failure Shock

How is dopamine administered?

IV drip infusion

What receptors does dobutamine act on? How does it differ from dopamine?

Dopaminergic receptors | more cardioselective

What are some examples of Bypyridines?

Inamrinone (Inocor)- used to be amrinone | Milrinone (Primacor)

What else are bipyridines referred as?

Phosphodiesterase inhibitors

How do bipyridines work?

Increase intracellular levels of cAMP Increase intracellular levels of Ca++ Increase myocardial contractility

What are the results of long-term use of bipyridines?

Significantly higher mortality than seen in untreated patients; therefore it's only used in short-term (acute) HF patients such as patients struggling to come off bypass

What is the first line of defense for the Tx of HF?

Diuretics; particularly furosemide (lasix); ideal for those nasty symptoms of excessive venous pressure

Right sided heart failure symptoms

``` Fatigue Increase in peripheral venous pressure Enlarged liver and spleen Distended jugular veins anorexia and complaints of GI stress swelling in hands and fingers dependent edema ```

Right sided failure

Left sided heart failure symptoms

``` Paroxysmal Nocturnal Dyspnea Elevated PCWP Pulmonary congestion (cough, crackles, wheezing, tachypnea) Restlessness Confusion Orthopnea Tachycardia Exertional Dyspnea Fatigue ```

Left sided failure

Orthopnea

Breathlessness when lying flat

How do diuretics help treat HF?

Little/no direct affect on heart Decrease plasma volume -decrease afterload and blood pressure -decrease preload as well as edema

What is the net affect of diuretics in tx of HF?

Decrease the heart's workload nad resulting myocardial demand

Diuretics affect what pressures how....

``` Decrease SBP (decrease afterload) Decrease DBP (decrease preload) ```

How do renin-angiotensin converting enzyme blockers treat HF?

Decrease venous tone, decrease SVR | Decrease preload and afterload

What is the drug of choice at all stages of HF? (Particularly in patients with low EF)

Renin-angiotensin converting enzyme blockers

Initiation of what Tx after AMIs is widely considered the standard of care?

ACE-Inhibitor Rx

What is an example of an angiotensin receptor blocker?

Losartan (Cozaar)

When is Losartan (Cozaar) typically used?

Not the first line drug; used as replacement for ACE-Inhibitors in intolerant patients; may laso be used with ACE-Inhibitors in decompensating patients

How doe primary vasodilators work to treat HF?

``` Dilation= decreased preload due to increased venous capacitance Dilation= decreased SVR and decreased afterload ```

What are the drugs of choice venous dilators for acute CHF episodes?

Nitrates

What are examples of primary vasodilators?

Hydralazine (apresoline) | Isosorbide (Isordil)

Why do those intolerant of ACE-Inhibitors and Angiotensin blockers or B blockers frequently respond to primary vasodilators?

works through a different mechanism

Why would you be giving negative inotropes to patients in HF?

Block chronic/deadly SNS stimluation which contributes to cardiomyocyte apoptosis and mitogenic remodeling Negative chronotrope= decrease myocardial oxygen needs

What are examples of beta blockers shown to improve long-term survivability in HF?

Metoprolol (Lopressore, Toprol-XL) Carvedilol (Coreg) (Not for acute HF, ex. would kill someone with a recent MI)

What are the two aldosterone antagonists?

Spironolactone (Aldactone) | Eplerenone (Inspira)

What is a direct aldosterone antagonist?

Spironolactone (Aldactone)

What is a competitive aldosterone antagonist?

Eplerenone (Inspra)

How do aldosterone antagonists help treat heart failure?

Prevent salt~ fluid retention, myocardial hypertophy and decrease K+ Improve long-term survival mortality post MI

What is an experimental drug combo showing great promise in treating HF?

LCZ696

What is LCZ696?

Experimental drug combo: | 50/50 mix of Losartan and Sacubitril

What is sacubitril metabolized into?

Neprilysin inhibitor

What is sacubitril?

An experimental antihypertensive

Neprilisyn

enzyme which breaks down atrial (ANP) and brain (BNP) natriuretic pepties

When is atrial natriuretic peptides (ANP) mostly released?

In reponse to excessive blood volume (mostly in response to excessive atrial stretch)

What does release of atrial natriuretic peptides (ANP) cause?

Increased GPR, increased sodium loss, and decreased renin secretion

ACC/AHA Stage Classification System for Tx with Chronic Heart Failure

A- Best B C D-Worst

NYHA Class system for Tx of CHF

Prefailure- best 1 2/3 4- worst

What is the role of morphine in treating CHF?

Classically used in acute heart failure to reduce preload, heart rate, and afterload; no evidence it helps and has worse long term outcomes. Lowers RR, decreases cardiac workload decreases preload nad afterload Eases anxiety!