Pharmacotherapy for Heart Failure

Question 1

Preload is controlled by?

Answer 1

Ventricular filling

Question 2

Afterload is controlled by?

Answer 2

Arterial pressure (TPR)

Question 3

bowditch is?

Answer 3

the subsequent increase in contractility with increased HR

Question 4

Anrep is?

Answer 4

the subsequent increase in contractility with increased afterload

Question 5

In long term HF what is the worst causative issue in people?

Answer 5

Sympathetic system activation due to low CO caused by HF

-stimulates more load and more cardiac remodeling

Question 6

Frank starling relationship to contractile status:

Answer 6

linear - increase preload = increase in contractility up to some point

Question 7

Stage A HF - patient descritpion:

Answer 7

(HIGH RISK FOR HF)

• HTN
• CAD
• DM
• FMx of cardiomyopathy

Question 8

Stage B HF - patient descritpion:

Answer 8

(ASYMPTOMATIC HF)

• Previous MI
• LV systolic dysfunction
• Asymptomatic valvular disease

Question 9

Stage C HF- patient description:

Answer 9

(SYMPTOMATIC HF)

• known structural heart disease
• shortness of breath and fatigue
• reduced exercise tolerance

Question 10

Stage D HF - patient description:

Answer 10

(REFRACTORY END STAGE HF)

• marked symptoms at rest despite maximal med therapy
• cant safely discharge these people from the hosptial

Question 11

Cardiac remodeling starts in which stage?

Answer 11

STAGE A - RIGHT AWAY SLOW PROCESS THAT JUST MAKES IT WORSE UNTIL YOU PROGRESS TO SYMPTOMATIC HF

Question 12

Drugs for Stage A:

Answer 12

ACEI or ARB

Question 13

Drugs for Stage B

Answer 13

ACEI or ARB

Beta-blocker

Question 14

Drugs for Stage C:

Answer 14

ACEI or ARB
Beta blocker
Diuretics
aldosterone antagonist
hydralazine and nitrates
Digoxin

Question 15

Drugs for Stage D:

Answer 15

ACEI or ARB
Beta blocker
Diuretics
Digoxin
Positive inotropes (drugs that inc cAMPs); dobutamine (Beta1 agonist)

Question 16

Heart failure is when what two types of symptoms converge?

Answer 16

congestive and low output symptoms

Question 17

Factors controlling intrinsic myocardial contractility:

Answer 17

1) beta receptor agonists binds –> g-protein –> cAMP made
2) activate PKA –> activate calcium channels = more calcium
3a) calcium stimulates release of more calcium from SR
3b) calcium is sequestered
lusitropic and inotropic

Question 18

**Practical approaches to increase myocardial contractility:

Answer 18

1) increase cytosolic Ca using cardiac glycosides (Digitalis)
2) increased myocardial cAMP concentration using phosphodiesterase inh (amrinone, Milrinone)
3) agonism at beta1 receptors using beta adrenergic agonists (Isuprel, dobutamine, dopamine, epinephrine, NE)
4) increase beta1 receptor density using beta receptor antagonist (metoprolol and carvedilol)

Question 19

Digoxin -

• type of drug?
• what does it do/MOA?

Answer 19

• glycoside - positive inotrope
• blocks the cardiac Na(out)/K(in) ATPase=accumulation of Na inside cell = reduced activity of Na(in)/Ca(out) exchanger leading to increased influx of Ca from extracellular space = enhanced contraction

Question 20

Digoxin - cardiac effects:

Answer 20

1) pos inotropic effect=
a) dec EDV and dec ESV
b) dec pulmonary and systemic venous pressure
c) reflex dec SANS = dec preload, afterload and HR)
2) direct pos vagal effect:
a) inc vagal tone = decrease AV conduction (USED FOR ATRIAL FIB)
b) inc PR interval (longer ERP)
c) dec APD ( shorter QT)
3) inc coronary flow (dec hypertrophy)
4) dec renal artery resistance (inc RBF–> Inc GFR –> inc UO)
5) Proarrhythmic - Inc PR and dec QT intervals - more severe arrhythmias (TYPICAL HOCKEY STICK) - ST depression

Question 21

Digoxin - pharmacokinetics

Answer 21

• *-T1/3 = 36-48hrs
• *-excreted by the kidney-affected by Rx that change renal RBF
• *-near steady state blood level ~7days
• inactivated by eudacterium lentum (intestinal bacteria some people have = less effect)
• plasma concentratin affectd by many drugs - CV Rx= antiarrhythmics class Ia and IV, spironolactone, vasodilators; cimetidine

Question 22

Digoxin- adverse effects:

Answer 22

• -low margin of safety (lethal dose is 5-10x minimal effective dose
• -electrolyte disturbances (hypokalemia) and acid-base disbalance –> susceptibility to side effects –> monitor plasma K
• -arrhythmias
• poor compliance
• visual and neuro disturbances
• -CTZ stimulation induces anorexia, nausea, vomiting

Question 23

Especially careful when using digoxin with what kind of drugs?

Answer 23

K-excreting drugs - diuretics - or loop diuretics,

ACEI,spirnonolactone, amiodarone, inc K serum

Question 24

Digoxin in Tx of HF:

Answer 24

• used frequently** especially CHF with Af

- DOES NOT improve all-cause mortality –> no longer a first line therapy

Question 25

Correctin of adverse elevations in plasma digoxin (arrhythmias)

Answer 25

• *cholestyramine
• *-digoxin immune Fab (des-IgG):
• – binds to both bound and free cardiac glycoside where it is sequested in extracellular fluid and eliminated thorugh the kidneys
• – administered IV - **immediate onset of action
• –toxicity reversal within minutes
• –**clinical effects also reverse

Question 26

phosphodiesterase 3 inh -

• Drugs?
• MOA?

Answer 26

• inamrinone and milrinone
• MOA: cyclic AMP-PDE inhibitors decrease cellular cyclic AMP degredation resulting in elevated levels of cyclic AMP in cardiac and smooth muscle myocytes`

Question 27

phosphodiesterase 3 inhibitors-

-cardiovascular effects:

Answer 27

-directly stimulate myocardial relaxation
-accelerate myocardial relaxation
-balanced arterial and venous dilation
===> dec TPR, PVR,
===> dec LV, RV pressures
========> ALL = increase CO

Question 28

phosphodiesterase 3 inhibitors:

-therapeutic uses:

Answer 28

• short half lives

* ** -approved for short term circulation support in advanced congestive HF

Question 29

ACEI

1) Mortality rate?
2) exercise tolerance?
3) quality of life?

Answer 29

1) dec 20%
2) mild improvement
3) mild improvement

Question 30

Beta-blocker

1) Mortality rate?
2) exercise tolerance?
3) quality of life?

Answer 30

1) dec 35%
2) mild or no improvement
3) mild or no improvement

Question 31

aldosterone antagonist

1) Mortality rate?
2) exercise tolerance?
3) quality of life?

Answer 31

1) dec 30%
2) mild or no improvement
3) mild improvement

Question 32

digoxin

1) Mortality rate?
2) exercise tolerance?
3) quality of life?

Answer 32

1) no effect
2) mild improvment
3) unk

Question 33

diuretic

1) Mortality rate?
2) exercise tolerance?
3) quality of life?

Answer 33

1) unk
2) moderate improvement
3) moderate improvement