Drugs for Heart Failure

Question 1

excitation - contraction coupling machinery of heart

Answer 1

primary defect

Question 2

baroreceptor reflex, SANS, kidneys, AG2, aldosterone, apoptosis of cardiac cells

Answer 2

secondary defect

Question 3

compensation in heart failure #1

Answer 3

Baroreceptor reflex increases sympathetic system:

1) increase contractility & HR (B1 adrenergic receptor)
2) increase vasomotor tone (A1 adrenergic receptor) to maintain systemic BP (inc. preload & inc. afterload)

Question 4

compensation in heart failure #2

Answer 4

RAAS activated:

1) AG2 constricts artery - inc afterload & constricts vein - inc preload
2) aldosterone causes Na+/H2O retention - inc preload (edema)
3) AG2 increases fibrosis in heart (collagen)

Question 5

Signs & Symptoms of Heart Failure

Answer 5

1) tachycardia
2) decrease exercise tolerance & SOB
3) peripheral & pulmonary edema (from LHF)
4) myocardial hypertrophy (initially helps maintain cardiac performance), [later leads to ischemic changes, impairment of diastolic filing, remodeling by local AG2 & aldosterone]

Question 6

1) increases connective tissue proliferation
2) Beta myosin fetal cells
3) eventually apoptosis

Answer 6

remodeling

Question 7

decrease ejection fraction

<50% (dilated/congestive)

Answer 7

systolic heart failure

Question 8

loss of adequate relaxation

Answer 8

diastolic heart failure

Question 9

Direct effects of Digoxin

Answer 9

• ** inhibition of cardiac Na+/K+ ATPase ***
  1) Inc intracellular Na+
  2) Dec Na+/Ca2+ exchange
  3) Inc intracellular Ca2+
  4) Inc Ca2+ release from sarcoplasmic reticulum
  5) Inc actin - myosin interaction
  6) Inc contractile force

Question 10

Indirect effect of Digoxin

Answer 10

inhibition of neuronal Na+/K+ ATPase (results in increase vagal activity)

Question 11

Decrease ESV
Increase SV & CO
Increase renal perfusion

Answer 11

First dose effect of Digoxin

Question 12

Decrease EDV (preload) in continued use
Continued large SV

Answer 12

Continued use of Digoxin

Question 13

Autonomic Effects of Digoxin

Answer 13

Increase of intracellular Ca2+ –> Inc Ach in PANS (M2) –> Dec HR –> Dec SA, A-V conduction (Tx: SVT)

Question 14

Effects of Digoxin on GIT (early signs)

Answer 14

Anorexia
Nausea
Vomiting
Diarrhea

Question 15

Effects of Digoxin on CNS (late signs)

Answer 15

Disorientation
Visual Effects (hallucinations)
Altered color perception (blue/green)

Question 16

ECG changes with Digoxin

Answer 16

1) Initial early shortening of AP
2) long term use - lengthening of AP
3) Increase PR interval d/t decrease AV cond vol
4) less -ve RMP - easy premature depolarization

Question 17

toxic dose effects of digoxin

Answer 17

any cardiac arrhythmias, bigeminy ventricular premature contraction

Question 18

What 3 factors cause - Increase Digoxin toxicity

Answer 18

hypokalemia
blood magnesium decrease
blood calcium increase

Question 19

what 3 factors cause - decrease digoxin toxicity

Answer 19

hyperkalemia
blood magnesium increase
blood calcium decrease

Question 20

Important key btwn K & digoxin

Answer 20

K & digoxin inhibit each other’s binding to Na/K ATPase b/c they compete with each other

Question 21

management of digoxin toxicity

Answer 21

Fab antibodies

Question 22

Quinidine interaction w/ digoxin

Answer 22

replaces digoxin from tissue protein binding & increases serum digoxin

Question 23

verapamil interaction w/ digoxin

Answer 23

increase digoxin concentration by: 1) decrease its. clearance; 2) replaces it from tissue protein binding

Question 24

Pharmacokinetics of digoxin

Answer 24

1) renal clearance- caution in renal impairment
2) long t1/2 - 1.5 days (min. 6 day -Css)
3) large vd - tissue protein binding

Question 25

MOA: Increase cAMP | only given IV for short term therapy

Answer 25

Phosphodiesterase inhibitors: Inamrinone and Milrinone

Question 26

Use for PDE inhibitors

Answer 26

Acute CHF

Question 27

MOA of PDE inhibitors

Answer 27

Increase cAMP on heart - increase inotropy | Increase cAMP on smooth muscle - decrease TPR

Question 28

ADR of PDE inhibitors

Answer 28

GI upset Thrombocytopenia liver toxicity

Question 29

Sympathomimetics used for Acute CHF (systemic fxn decreases)

Answer 29

Dobutamine (B1 adrenergic agonist) | Dopamine

Question 30

Drugs that decrease mortality in HF

Answer 30

1) ACE-I, ARB 2) B-Blocker 3) Spironolactone/Eplerenone 4) Carvedilol 5) Vasodilators: Nesiritide and Bosentan

Question 31

recombinant human BNP, for acute decompensated CHF | ADR: decrease BP

Answer 31

Nesiritide (vasodilator)

Question 32

Endothelin receptor blocker

Answer 32

Bosentan

Question 33

decrease AG2 > + vasodilation decrease aldosterone > decrease fluid retention slows cardiac remodeling

Answer 33

angiotensin antagonist

Question 34

Diuretics in HF

Answer 34

1) Furosemide - decrease volume immediately in pulm congestion and severe edema secondary to acute HF 2) Hydrochlorothiazide - mild chronic failure 3) Spironolactone/Eplerenone - long term benefits and decrease mortality in chronic HF

Question 35

1) secreted by ventricular myocytes secondary to stretch 2) increase HF 3) binds to receptor on plasma membrane in vasculature, kidney and other organs

Answer 35

BNP

Question 36

-ve Sa node funny channel > decrease HR but does not suppress heart contraction

Answer 36

Ivabradine

Question 37

enzyme to degrade BNP and bradykinin

Answer 37

neprilysin

Question 38

neprilysin derivative | decreases morbidity and mortality

Answer 38

sacubitril

Question 39

symptoms of acute LHF

Answer 39

``` orthopnea dyspnea pink sputum sweating anxiety ```

Question 40

sign of LHF

Answer 40

whole lung rales Gallop HR cyanosis

Question 41

CXR of LHF

Answer 41

cardiomegaly | butterfly infiltration

Question 42

management of acute LHF

Answer 42

1) O2 2) morphine 3) furosemide 4) digoxin 5) nitroprusside 6) life support 7) treat the cause

Question 43

Stages of HF

Answer 43

1) SOB with heavy exercise 2) SOB with ordinary activities 3) SOB with less than ordinary activities 4) SOB at rest