Fast upstroke - Na+ channels open - Na+ current is blocked by anti-arrhythmic drugs

Topic 10 Flashcards by melissa griffith

Heart Failure definitions

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

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Symptomatic definition for heart failure

A mismatch between right and left heart volume

outputs: Right sided vs. Left sided HF
- implies 2 different set of syndromes

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Cardio-centric definition for heart failure

The heart’s impaired ability to adequately
fill with &/or eject blood
-implies dual causation

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Definition of what causes heart failure

systolic failure= thin walls
diastolic failure= thick walls
-implies 2 types of myocardial remodeling

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Systolic HF=

decreased Contractility
decreased Ejection Fraction
~ ½ of the HF patients which tend to be “younger”

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Diastolic HF=

decreased Ventricular Filling
decreased Cardiac Output
~ ½ of patients which tend to be older

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Main HF causes

1) Ischemia
2) Idiopathic
3) Viral
4) Immune-mediated
5) HTN

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Ischemia can contribute to

both systolic and diastolic dysfunction

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Most common type of HF in America? %?

Ischemia

70%

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Idiopathic=

Familial? (~ 1/3?)
Toxins?
Parasitic?
Undiagnosed viral?
Pregnancy-related?

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Viral=

Viruses “errantly” take up residence in
myocardial cells…Moderate/severe cardiomyopathy develops…and may or may not fully or completely
resolve (eventually)
•Might require valvular Sx due to new cardiac “geometry”

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Immune mediated

Specific cardiac antibodies attack cardiomyocytes
•Possible link to other immune-mediated diseases
•Acute myocardial infarctions (AMIs) may expose novel cardiac antigens affecting long-term prognosis

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Phase 0

Fast upstroke

Na+ channels open
Na+ current is blocked by anti-arrhythmic drugs

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Phase 1

Partial re-polarization

-Inactive Na+ channels, Fast Active K+

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Phase 2

Plateau

-Ca++ opens

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Phase 3

Re-polarization

-Ca++ close, K+ open

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Phase 4

Forward current

-increasing depolarization from gradual increase in Na+

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What forces contribute to the chronic downhill HF slide?

#1= ANS
#2= Renin-Angiotensin-Aldosterone system

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Why Does the Heart “Remodel”?

Heart cells die…they’re replaced with fibrotic tissues…and remaining cells hypertrophy.

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What are the Goals of Therapy for HF?

1) Improve/alleviate critter’s symptoms
2) Slow that “downhill slide” towards
transplant/VAD/death
3) Improve survival
4)Increase critter’s QALYs

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Six Classes of QALY-Improving Drugs

1) Positive Inotropes
2) Diuretics
3) Renin/Angiotensin Blockers
4) Primary Vasodilators
5) β-Blockers
6) Aldosterone Antagonists
7) Neprilysin Inhibitor (the future?)

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1: Positive Inotropes=

Cardiac Glycosides
Catecholamines
Bipyridines

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Cardiac Glycosides: drug name

Digitalis (Digoxin)

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Digitalis

Digoxin

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Digitoxin (historical use)

Positive Inotrope Negative Chronotrope Increased Baroreceptor sensitivity

Cardiac Glycosides Narrow therapeutic window for

Arrhythmias, GI symptoms

Digitalis blocks

Na⁺/K⁺ -ATPase “The Sodium Pump”

Administration of Digoxin shifts the ventricular function curve toward

normal

Digoxin treatment effects on the heart

Increased contractility and CO | Decreased sympathetic reflexes and vascular tone= decrease in ventricular end diastolic pressure

decompensated HF=

1. initial contractility due to HF | 2. symptoms of low CO (Dyspnea, edema)

compensated HF=

1. ventricular end diastolic pressure increase in an effort to maintain adequate CO 2. Symptoms of congestion (Dyspnea)

Catecholamines are classic

β-1 adrenergic receptor stimulants

Catecholamines- drugs

Epinephrine Norepinephrine Dopamine Dobutamine

Catecholamines are powerful

positive inotropes and chronotropes

PREFERRED DRUG FOR CARDIAC ARREST

Epinephrine (Adrenaline)

Epinephrine (Adrenaline) is handy for _____ reactions and has predictable ______ ______

anaphylactic | side effects

Dopamine is a relatively non-specific ______ and acts on ______ receptors

catecholamine | dopaminergic

Dopamine improves cardiac function in _____ and is also used for ____ and ____

heart failure renal failure shock

Dopamine is given by

IV drip infusion

Dobutamine also acts on dopaminergic receptors is but | more

cardioselective

Bipyridines are referred to as

phosphodiesterase inhibitors

Bipyridines: drugs

Inamrinone (Inocor) | Milrinone (Primacor)

Inamrinone

(Inocor)

Milrinone

(Primacor)

Bipyridines have what effects

increase intracelular levels of cAMP= increased intracellular levels of Ca⁺⁺ = increased myocardial contractility

Bipyridines: ***Surprisingly, longer-term use of these drugs results in

significantly higher mortality than that seen in untreated patients!

Bipyrides are only used in

short-term (acute) HF patients

#2: Diuretics: First-line D.O.C.’s for

heart failure (particularly furosemide/lasix)

Diuretics: drugs

furosemide (lasix)

furosemide

lasix

Diuretics are ideal for nasty symptoms of excessive

venous pressure

Diuretics Decrease plasma volume, which does what

Decrease afterload and blood pressure Decrease preload as well as edema *Net affect is to decrease the heart’s workload and mycardial O2 demand

#3: Renin-Angiotensin Converting Enzyme Blockers (Angiotensin-Converting Enzyme Inhibitors) have what effects

decrease venous tone which in turn decreases SVR. | decreases preload & afterload

Renin -Angiotensin Converting Enzyme Blockers: DOC

- all stages of HF, particularly in patients with low EF | - Often used as part of a progressive multi-modal Rx

initiation of ACE-Inhibitor Rx after _____ is widely considered a standard of care

acute myocardial infarction

Angiotensin Receptor Blockers “ARBs”: Historically | not a first-line drug- Used as a

replacement for ACE-Inhibitors in intolerant patients BUT may also be used with ACE-Inhibitors in decompensating patients

Angiotensin Receptor Blockers: drug name

Losartan (Cozaar)

Losartan

(Cozaar)

#4: Primary Vasodilators: have what effects

Dilation = - decreased preload due to increased venous capacitance - decreased SVR - decreased afterload

Primary Vasodilators: _____ are frequently D.O.C. venous dilators for acute CHF episodes

Nitrates

Those intolerant of ACE-Inhibitors and Angiotensin Blockers &/or β-Blockers frequently respond well to

Hydralazine (Apresoline) | Isosorbide (Isordil)

Hydralazine

(Apresoline)

Isosorbide

(Isordil)

#5: β-Blockers: Block chronic (and deadly) SNS stimulation which contributes to

cardiomyocyte apoptosis | mitogenic remodeling

B-Blockers have what effects

Negative chronotrope= decreased myocardial O2 needs

β-Blockers: Drugs

Metoprolol (Lopressor, Toprol-XL) | Carvedilol (Coreg)

Metoprolol

(Lopressor, Toprol-XL)

Carvedilol

(Coreg)

β-Blockers: Metoprolol and Carvedilol- have been show to improve

long-term HF survivability. NOT for acute HF!!!

#6: Aldosterone Antagonists: have what effets

help prevent salt/fluid retention, myocardial hypertrophy, and K⁺ *Improve long-term mortality post-MI

Aldosterone Antagonists: drugs

Spironolactone (Aldactone) | Eplerenone (Inspra)

Spironolactone

(Aldactone)

Spironolactone (Aldactone) is a

DIRECT aldosterone antagonist

Eplerenone

(Inspra)

Eplerenone (Inspra) is a

COMPETITIVE aldosterone antagonist

#7: LCZ696: A 50/50 mix of

Losartan and Sacubitril | •Sacubitril is metabolized into a neprilysin inhibitor

LCZ696: Neprilisyn is an enzyme which breaks down

atrial (ANP) & brain (BNP) natriuretic peptides

ANP is mostly released in response to

excessive blood volume (mostly in response to excessive atrial “stretch”) and causes an increased GFR, increased sodium loss, and decreased renin secretion

Stage A (Pre-faliure) - Description - Management

- Description: No symptoms but risk factors present | - Management: Treat obesity, HTN, Diabetes, Hyperlipidemia

Stage B (I) - Description - Management

- Description: Symptoms with severe exercise | - Management: ACEI/ ARB, B-Blocker, Diuretic

Stage C (II/III) - Description - Management

- Description: Symptoms with markes (Class II) or mild (class III) exercise - Management: Add aldosterone antagonist, digoxin, CRT, hydralazine/nitrate

Stage D (IV) - Description - Management

- Description: Severe symptoms at rest | - Management: Transplant, LVAD

Morphine used in acute heart failure to

reduce preload, heart rate, and (maybe?) afterload

Morphine has what effects for chronic HF

1. Lowers respiratory rate which decreases cardiac workload 2. Decreases preload and afterload 3. EASES ANXIETY!