L 29-30

Question 1

Causes of low output CHF

Answer 1

CAD
HT
MI
Persistent Arrhythmias
Rheumatic HD
General Cardiomyopathy

Question 2

CHF and RAAS

Answer 2

Poor CO => poor renal perfusion=> production of Renin and activation of RAAS to increase blood volume

Question 3

CHF and SNS

Answer 3

Poor CO=> decreased systolic BP=> neurohumoral response=> increase in HR

Question 4

CHF and preload

Answer 4

In CHF preload on the heart is increased due to increased blood volume from the RAAS system and increased SNS tone.

Question 5

CHF and afterload

Answer 5

In CHF afterload rises from RAAS and increased SNS tone

Question 6

CHF and contractility

Answer 6

Contractility is decreased as ventricles dilate and stretch farther than normal.
Contractility increased by positive inotropic agents and worsened by Beta blockers.

Question 7

Equation for CO

Answer 7

CO= HR x SV

Question 8

CHF and HR

Answer 8

Heart Rate is generally increased because reduced CO=> baroreflex=> increased SNS tone causing increased HR.

Question 9

Factors controlling contractility

Answer 9

Sensitivity of contractility proteins to Ca
Amount of Ca released from SR
Amount of Ca stored in SR
Amount of trigger Ca
Activity of Na-Ca exchanger
Intracellular Na concentration and activity of Na-K ATPase

Question 10

Explain cardiac myocyte electrolyte transport and activity at the cell membrane

Answer 10

Na/K ATPase maintains a high Na concentration outside the cell. This gradient is used to exchange Na into the cell for Ca out of the cell.
Ca is allowed into the cell and to act as trigger Ca by L-type voltage-gated Ca channels.

Question 11

Site of action for cardiac glycosides

Answer 11

NA/K–ATPase in the cardiac myocyte

Question 12

Describe Ca channels in the SR of the heart

Answer 12

SERCA: A Ca ATPase that transports Ca into the SR
RyR: (ryanodine receptor) Ca gated Ca channel that releases Ca from the SR

Question 13

Main goals of drug treatment in CHF and drug classes used for each

Answer 13

1) Reduce preload with diuretics and venodilators
2) Reduce afterload with arteriodilators
3) Improve contractility with positive inotropic drugs
4) Decrease HR and energy expenditure of the heart with Beta blockers

Question 14

What are cardiac glycosides?

Answer 14

Positive inotropic agents commonly called Digitalis.
Only version of this drug in the US is Digoxin.
These act on the Na/K–ATPase in the cell membrane of cardiac myocyte

Question 15

Mechanism of action for cardiac glycosides

Answer 15

Digitalis (Digoxin) is a positive inotropic agent that increases contractility by increasing rate of contraction and relaxation.

Digitalis binds to the K+ site of the NA/K–ATPase and prevents function
=> increased intracellular Na
=> decreased Ca expulsion
=> increased intracellular Ca
=> decreased intracellular K & increased actin/myosin interaction=> increased contractility

Question 16

Potassium and Digitalis interaction

Answer 16

K and Digitalis compete for binding site on Na/K–ATPase.
Potassium is a competitive inhibitor of Digitalis and is an effective treatment of Digitalis toxicity.
Potassium is useful in decreasing the automaticity of the heart by pumping more Na out which causes more Ca to also be pumped out=> decreased actin/myosin interaction.

Question 17

Effect of Ca levels and digitalis

Answer 17

Ca enhances the effect of Digitalis and therefore should never be used in cases of Digitalis toxicity

Question 18

Digitalis and HR

Answer 18

Digitalis will always reduce HR, but it only affects CO in the failing heart, but no effect in the healthy heart.
In failing heart, increased contractility=> increased CO=> decreased baroreceptor response=> decreased SNS tone and decreased HR

Question 19

Digitalis and vascular effects

Answer 19

Normal Heart: causes contraction of smooth muscle => vasoconstriction (why there is no change in CO in normal patients despite decrease in HR)

Failing Heart: causes vasodilation due to reduced baroreceptor firing and decreased SNS output

Question 20

Digitalis Pharmacokinetics:

Oral availability, Half-life, Renal elimination

Answer 20

Oral Avail: 75%
Half-life: 40 hours
Renal Elim: >80%

Question 21

Adverse effects of Digitalis in GI tract

Answer 21

Anorexia, diarrhea, vomiting, abdominal pain

Question 22

Earliest signs of digitalis intoxication

Answer 22

GI symptoms as well as copius salivation

Question 23

How safe is Digitalis?

Answer 23

Has a narrow margin of safety– therapeutic dose is 50% of toxic dose. Toxicity is common. Most severe effect is cardiac toxicity leading to death.

Question 24

Adverse effects of Digitalis

Answer 24

Most serious effects are cardiac: Bradycardia, Ectopic ventricular beats, AV block, Bigeminy (PVB’s, T-wave inversion, ST depression)

Question 25

Digitalis drug interactions

Answer 25

Diuretics: loop and thiazide cause hypokalemia=> enhanced effects Beta blockers: decrease SA and AV node conduction predisposing for AV block Ca Channel antagonists: decrease contractility Catecholamines: sensitize myocardium to digoxin

Question 26

Name Phosphodiesterase inhibitors (bipyridines) and how they work.

Answer 26

Inamrinone & Milrinone Inodilators: meaning they are inotropic and vasodilators Work by inhibiting cAMP phosphodiesterase in cardiac and vascular muscle which usually breaks down cAMP. Helps by improving diastole and contractility along with vasodilation.

Question 27

Use of bipyridines

Answer 27

Not used often. Not shown to be safe or effective in long-term treatment of heart failure.

Question 28

Name positive inotropic sympathomimetic agents

Answer 28

Dopamine Dobutamine Calcium Sensitizers

Question 29

Dopamine use as inotropic agent

Answer 29

Used in severe refractory CHF Low doses=> increased CO (pos inotropic effect) and increased renal perfusion Lowers peripheral resistance Enhances Na excretion

Question 30

Dobutamine characteristics

Answer 30

Selective beta-1 agonist | Positive inotropic with less tachycardia

Question 31

Classes of drugs used for CHF that don't have a positive inotropic effect.

Answer 31

1) Diuretics 2) ACE inhibitors 3) Beta Blockers 4) Vasodilators

Question 32

Name potassium sparing diuretics used in CHF

Answer 32

Amiloride: inhibits ENaK function in principle cells, can lead to hyperkalemia when combined withACE inhibitors or ANG II antagonists Spironolactone: also inhibits aldosterone receptors

Question 33

Explain B type natriuretic peptide

Answer 33

hBNP: produced by ventricular muscle, prepared for use in acute treatment of decompensated CHF. Works to reduce pulmonary capillary wedge pressure and relieve CHF symptoms of fatigue and dyspnea Monitor closely to prevent hypotension

Question 34

What is pulmonary capillary wedge pressure?

Answer 34

Pressure measured in a pulmonary artery that is used to estimate the pressure in the left atrium. Elevations indicate failure of the left ventricle and backup of pressure into the atrium.

Question 35

Three general effects of Angiotensin II

Answer 35

1) Vasoconstriction and increase rate of pressor response 2) Altered kidney function (increase Na absorption, aldosterone release and effects, renal vasoconstriction) 3) Cardiac and vascular remodeling (increased growth hormone production, increased ECM production, increased vascular tension)

Question 36

Why/how are ACE inhibitors and ANG II antagonists helpful in CHF?

Answer 36

Both reduce RAAS. This is helpful because it decreases the afterload on the heart from vasoconstriction by ANG II and it decreases the preload by inhibiting aldosterone release and increased fluid retention.

Question 37

Beta blocker use in CHF

Answer 37

Dangerous because of neg inotropic effect Useful to enhance diastolic function and ejection fraction. Also reduces cardiac remodeling.

Question 38

Vasodilators used for CHF

Answer 38

Sodium Nitroprusside: IV administration for acutely decompensated CHF, dilates both arteries and veins, can cause hypotension Nitroglycerin or Isosorbide Dinitrate: orally, dilates veins more than arteries, tolerance develops Hydralazine: relaxes arteriolar smooth muscle=> reflex increase in HR, increase CO, Increase LV ejection fraction, tolerance can develop Long term use of hydralazine and isosorbide dinitrate can reduce damaging remodeling of the heart