Exam 1: Lecture 9: Heart Failure 2

Question 1

What % of CO should kidney get?

Answer 1

about 25%

Question 2

3 Categories of drugs used in HF

Answer 2

Positive Inotropic drugs

Vasodilators

Misc drugs for chronic failure

Question 3

Ways in increase isotropy?

Answer 3

Sympathetic Activation

Circulating Catecholamines

Heart Rate (Bowditch effect)

Afterload (Anrept effect)

Parasympathetic (Vagal) Inhibition

Question 4

Positive Bowditch effect “staircase effect or Treppe effect”

Answer 4

Described by Henry Pickering Bowditch in 1871

Summarized: Tension of heart muscle will increase as HR increases.

leads to increase in CO, due to increased in Ca in SR…not enough time/efficiency in mechanisms that remove Ca between heart beat.

Main player = NCX (Sodium/Calcium exchanger)

Question 5

Woodworth effect

Answer 5

higher than normal systolic peak following Bowditch effect

Question 6

Negative Bowditch effect

Answer 6

Can be caused by some drugs

Increase in HR = decrease in tension

can be due to mutations or negative regulation of SERCA2a or phospholamban

Question 7

Anrep effect

Answer 7

myocardial tension increases with afterload

consistent with Frank-starling law.

Question 8

Digoxin (Lanoxin)

Answer 8

Cardiac glycoside, only one that’s currently clinically important

Comes from foxglove

Indicated: A.fib, HF and abortion
Mech: Positive inotrope, inhibit myocardial Na/K ATPase

No longer a 1st line heart failure

Side effects: Narrow TI, Atrial arrhythmia, A-V conduction block, Gynecomastia (feminization)

OD treated with anti-digoxin antibody

Question 9

Digoxin Mechanism of action

Answer 9

Inhibit Na/K-ATPase = Block Na leaving cell leaving it more depolarized, changing efficacy of NCX and increases Ca conc in cell, increases Ca release from SR and stimulates contractile machinery

Question 10

Oubain

Answer 10

Used to be used therapeutically but no more. Used experimentally

Positively inotropic, making Ca conc go way up = increase contraction.

Has very low TI

after period of time/inc conc it can cause secondary sub threshold AP = bad

Question 11

Dobutamine

Answer 11

B-receptor agonists
** B1-receptor specific agonist racemate **, considered B1-specific

usually IV

Positive inotrope that increases CO, little effect on HR

Indicated: cariogenic shock, septic shock and acute or potentially reversible HF

side effect: Hypertension, angina, tachyarrhythmia

Question 12

(+) isomer of Dobutamine effects on…

Answer 12

B1-agonist, a1-antagonist and a weak-agonist at B2 (vasodilator)

Question 13

(-) isomer of Dobutamine effects on…

Answer 13

B1-agonist and a1-agonist

Question 14

Phosphodiesterase inhibitors (PDEi)

Answer 14

Focus on Type3 (PDE), leading to accumulation of more cAMP by preventing it from being turned into AMP

Question 15

Cardiovascular actions of PDEi

Answer 15

increase systemic circulation via vasodilation

increase organ perfusion, decrease systemic vascular resistance and arterial pressure

Question 16

Cardiopulmonary actions of PDEi

Answer 16

increase contractility and HR (+ inotropic/chronotropic)

increase stroke volume and ejection fraction

decrease ventricular preload (2ndary to increased output)

Question 17

Milrinone

Answer 17

PDE3 inhibitor

a bipyridine available as Primacor

Indicated: HF or pulmonary arterial hypertension (RV into Lung) and also used in acute severe asthma

Side effect: Ventricular arrhythmia, hypotension, headache and dizziness

Question 18

Aldosterone Antagonists

Answer 18

“K+ sparing diuretics”

inhibit mineralocorticoid receptor upregulation, decreasing ENaC and Na/K+ ATPase in DCT, increasing Na/H20 excretion and K+ retention

Spironolactone has off target effects, Eplerenone is more specific but has lower Emax

Question 19

Spironolactone

Answer 19

“K+ sparing diuretic”

Competitive inhibitor of aldosterone receptor, also blocks effects of testosterone and other hormones

Indicated: HF, edema, primary hypertension. issues with androgens such as hirsutism and PCO

Indicated in HF where EJ < 35%

side effects: increased urination, hyponatremia, hypotension, Ataxia, Feminization

Question 20

Eplerenone

Answer 20

“K+ sparing diuretic”

More selective for receptor than spironolactone, but 50% Emax

Indicated: Chronic HF, primary hypertension

side effects: Increased urination, Hyponatremia, hypotension

Question 21

Atrial natriuretic peptide (ANP)

Answer 21

is release by cardiac atria when the muscle is stretched in response to expanded blood volume….promotes physiology that decreases BV

Question 22

Physiology that decreases Blood volume?

Answer 22

increase vasodilation, decrease production of aldosterone, increase natriuresis, diuresis, EJ and decrease BP

Question 23

3 major naturetic peptides

Answer 23

A,B and C naturetic peptides.

BNP secreted by heart ventricles

Question 24

How do naturetic peptides have effect?

Answer 24

Receptors are located on tissues throughout the body

Question 25

A-type naturetic receptor

Answer 25

Selective for ANP and BNP

Question 26

Nesiritide

Answer 26

Synthetic BNP, administered as IV

developed for acute decompensating HF

Overall, found it doesn’t really work more than placebo

Side effects: Hypotension, Headache, Bradycardia and Kidney failure

Question 27

Positive inotropic drugs?

Answer 27

Cardiac glycosides

Beta agonists

PDE inhibitors

Question 28

Vasodilators

Answer 28

PDE inhibitors

Nitrates, nitroprusside, hydralazine

Loop diuretics