Pharm 10-Heart Failure Flashcards
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
What is the symptomatic definition of heart failure?
A mismatch between right and left heart volume outputs
Cachexia
weakness and wasting of the body due to severe chronic illness.
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
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)
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
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”
Batista Procedure
Cut out part of the left ventricle going to renormalize geometry of the heart; great results at first but then very bad
What are the 5 main causes of heart failure?
- Ischemia
- Idiopathic
- Viral
- Immune Mediated
- HTN
What is the most common cause of heart failure?
ischemia; 70% type of HF in America
Ischemia contributes to which type of heart failure dysfunction?
both systolic and diastolic
Idiopathic
Unknown cause
About how common is familial causes in idiopathic heart failure?
1/3
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
Describe immune-mediated heart failure.
Cardiac antibodies attack cardiomyocytes
Link to other immune-mediate diseases
AMIs expose novel cardiac antigens affecting long-term prognosis
What forces contribue to the chronic downhill heart failure slide?
- Nervous system
2. Renin-angiotensin-aldosterone system
Why does the heart remodel?
Heart cells die and are replaced with fibrotic tissue and remaining cells hypertrophy
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)
6 Classes of QALY-Improving Drugs
- Positive inotropes
- Diuretics
- Renin/Angiotensin Blockers
- Primary Vasodilators
- B-Blockers
- Aldosterone Antagonists
- Neprilysin Inhibitor
What are the 3 types of positive inotropes?
- Cardiac Glycosides
- Catecholamines
- Bypyridines
What is an example of a cardiac glycoside?
Digitalis (Digoxin)
Describe the effects of Digitalis (Digoxin).
Positive Inotrope
Negative Chronotrope
Increased Baroreceptor sensitivity
Describe the therapeutic window of Digitalis (Digoxin)
Narrow therapeutic window (arrythmias, GI symptoms)
no evidence these drugs prolong life
How does Digitalis (Digoxin) work?
Blocks Na+/K+ -ATPase “The Sodium Pump”
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
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
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!
