Congestive Heart Failure (Exam III) Flashcards
What’s the 5 year mortality rate for heart failure?
50%
What is the most common cause of heart failure?
What is the progression of this disease process?
Coronary Artery Disease
CAD → Angina → MI → Scarring/Remodeling → HF
Differentiate systolic HF vs diastolic HF.
Systolic HF = reduced cardiac function (i.e. pumping)
Diastolic HF = reduced diastolic filling (usually hypertrophy)
What happens to Ejection Fraction (EF) in systolic vs diastolic failure?
Systolic HF: ↓ EF ↓ CO
Diastolic HF: ↓ CO, normal EF.
What is the rarest form of heart failure?
What 4 examples were given that can cause this heart failure?
“High-Output” Failure = normal CO, insufficient for bodily demands.
- Hyperthyroidism
- Beriberi disease
- Anemia
- Arteriovenous shunts.
How is End-Diastolic Volume (EDV) calculated?
Passive Filling + Atrial Contraction + End-Systolic Volume (ESV) = EDV
Ex. 65ml + 25ml + 50ml = 140ml EDV
How is stroke volume calculated?
EDV - ESV = SV
140ml - 60ml = 80ml
What 3 examples were given in lecture for decreasing preload?
- Na⁺ restriction
- Diuretics
- Venodilation (nitroglycerin, etc.)
Describe the pathologic positive feedback mechanism of heart failure associated with excessive afterload.
↓ CO = ↑ NE/Epi → ↑ afterload = ↓ CO
rinse and repeat
Which compensatory mechanism is the first to respond in a situation of decreased cardiac output (CO) ?
↑ Heart Rate
Which 3 mechanisms influence stroke volume?
Which of these 3 negatively affects CO?
Preload, contractility, and afterload.
↑ afterload = ↓ CO
Which pump is going to influx Ca⁺⁺ into the sarcoplasmic reticulum for storage?
SERCA (Sarcoplasmic Reticulum Ca⁺⁺ ATPase Pump)
What molecule binds to and holds Ca⁺⁺ in the sarcoplasmic reticulum?
CalS (Ca⁺⁺ Sequestrin)
In broad strokes, what is the process for Ca⁺⁺ to affect myocardial contractility?
- “Trigger” Ca⁺⁺ enters cell via action potential.
- Ca⁺⁺ binds to SR, releasing Ca⁺⁺ stores.
- Ca⁺⁺ binds w/ myosin = contraction
What 3 factors effect the amount of “trigger” Ca⁺⁺ that enters a sarcomere/myocardial cell?
- Amount of L-Type Ca⁺⁺ channels
- Duration of channel opening
- SNS stimulation.
How do β1 agonists affect trigger Ca⁺⁺ levels?
β-1 agonists ↑ time that Ca⁺⁺ L-channels are open = ↑ trigger Ca⁺ to enter the cell.
What drug has been stipulated as being both pro-arrythmic and anti-arrythmic?
Digoxin
What is the mechanism of action of digoxin?
- Digoxin binds to and inhibits Na⁺K⁺ATPase Pump.
- ↓ intracellular K⁺ = ↑ intracellular Na⁺
- Na⁺/Ca⁺⁺ antiporter is reversed.
- ↑ intracellular Ca⁺⁺
Which drug is a cardiac glycoside?
What is this drug used for?
What is it derived from?
What is its therapeutic index
- Digoxin
- Only + oral inotrope
- Foxglove plant
- Narrow TI = 2
What is the bioavailability of digoxin?
What is the T½ of digoxin?
What is the excretion of digoxin?
- 65-80%
- T1/2= 36-40 hours
- 2/3 excreted unchanged by kidneys
What are the electrical effects of digoxin?
What does toxic dosing of digoxin cause?
What is the “digitalis effect” on an EKG?
- ↑ PR interval, ↓ QT interval
- Tachycardia, fibrillation, cardiac arrest
- Downward “swoop” on ST segment
How does hyperkalemia affect digoxin?
How does this compare with hypercalcemia and hypomagnesemia?
↑ K⁺ competes with digoxin and decreases effect.
↑ Ca⁺⁺ and ↓ Mg⁺⁺ = arrhythmias
What does phosphodiesterase-3 inactivate?
Knowing this, what would a PDE-3 inhibitor do to these?
cAMP and cGMP
PDE-3 Inhibition = ↑ cAMP & ↑ cGMP
Which PDE-3 Inhibitor is a bipyridine?
How does this drug produce myocardial contraction and smooth muscle relaxation?
Milrinone
PDE-3 Inhibition:
1. ↑ cAMP = myocyte contraction
2. ↑ cGMP = smooth muscle relaxation
What should be known about the pharmacokinetics of milrinone (i.e. route of administration, T½, and site of excretion) ?
- Parenteral (IV) only
- T½ = 2-3 hours
- Urinary excretion
Why might a phosphodiesterase inhibitor be preferred over digoxin?
No inhibition of the Na⁺ K⁺ ATPase pump.
Which β agent is the most utilized drug for acute HF?
Dobutamine
Which drug class reduces preload, edema, and cardiac size?
How does this class accomplish this?
Is the process of reduction of cardiac size a rapid one?
- Diuretics
- Reduction of salt and H₂O retention
- Cardiac remodeling is a very gradual process.
Which two drugs might be good choices to reduce compensatory responses to decreased cardiac output (i.e. HF)?
ACE Inhibitors (Captopril) & ARBs (Losartan)
How do all vasodilators, to one degree or another, treat heart failure?
Reduction of preload & afterload
How do nitroprusside, hydralazine, and nitrates produce vasodilation?
Release of NO from drug or endothelium
How do verapamil, diltiazem, and nicardipine produce vasodilation?
Ca⁺⁺ influx reduction
How do minoxidil and diazoxide produce vasodilation?
↑ pK⁺ to hyperpolarize smooth muscle membrane.
How does Fenoldepam produce vasodilation?
Activation of dopamine receptors
How do β-blockers treat HF?
Which β-blockers are preferred for HF?
Should β-blockers be used in severe HF?
- Reduction of CO = less O₂ demand
- β-1 selective and/or vasodilatory (nebivolol)
- No
How do Ca⁺⁺ Sensitizers work?
↑ inotropy + vasodilate
* Stabilize Ca⁺⁺ bound conformation
* Open K⁺ channels (hyperpolarize cell)
Which drugs should be avoided in HF?
What is the exception?
- NSAIDs (except aspirin)
- Thiazolidinediones (Rosiglitazone & Pioglitazone)
- Metformin (causes lactic acidosis)
- Non-selective β-blockers for severe HF
What are the stages of heart failure?
- Stage A - High risk, no symptoms
- Stage B - Structural disease, no symptoms
- Stage C - Structural disease, symptoms
- Stage D - Refractory symptoms
What is the best treatment for Stage A heart failure?
Risk-factor reduction and education
If someone were to be treated for acute heart failure and be hyponatremic, would you use diuretics?
- No, could lower Na⁺ too much.
- Conivaptan (ADH inhibitor) instead.
