CHF Pharm

Question 1

According to ACC/AHA guidelines, a patient who is stage A can be characterized by what?

Answer 1

AT RISK for CHF

Question 2

According to ACC/AHA guidelines, a patient who is stage B can be characterized by what?

Answer 2

Low EF but no symptoms

Question 3

According to ACC/AHA guidelines, a patient who is stage C can be characterized by what?

Answer 3

edema and dyspnea

Question 4

According to ACC/AHA guidelines, a patient who is stage D can be characterized by what?

Answer 4

advanced heart failure

Question 5

How do you treat a stage A CHF patient?

Answer 5

1) Preventive Measures (treating hypertension, dyslipidemia, diabetes, stopping smoking and alcohol intake)
2) ACE inhibitor or ARB

Question 6

What do you add on to the treatment of a stage B CHF patient?

Answer 6

Other than preventative measures and ACEI/ARB, you use a beta blocker

Question 7

What do you add on to the treatment of a stage C CHF patient?

Answer 7

Preventative measures, ACEI/ARB, Beta blocker and add on diuretic/digoxin/spironolactone

Question 8

How do you treat a stage D CHF patient?

Answer 8

you need to give IV inotropes and transplant along with the other therapy

Question 9

What is the MOA of ACE inhibitors?

Answer 9

block angiotensin I to angiotensin II conversion in the lung

Question 10

Which ACE inhibitors are NOT prodrugs?

Answer 10

captopril and lisinopril

Question 11

What is the MOA of ARBs?

Answer 11

block AT1 receptors to induce vasodilation and increase Na+ and water excretion

Question 12

What is the ending to ARBs?

Answer 12

-tans (ex. losartan)

Question 13

What is the MOA of aliskiren?

Answer 13

directly inhibits the protease activity of renin

Question 14

Renin is released from the kidney to act on what chemical? What is this released from?

Answer 14

REnin is released from the kidney and converts angiotensinogen (from liver) to angiotensin

Question 15

ACE inhibitors lead to what effects?

Answer 15

• Decrease TRP (prevent vasoconstriction)
• Decrease aldosterone (natriuresis, loss of Na and fluids)
• Increase Bradykinin levels
• Increase prostaglandin production (increased vasorelaxation)

Question 16

What are the specs of ACE inhibitor use. (who do these work on, who do they not work on, contraindications)

Answer 16

• Not good for African Americans
• Not good for low-renin HTN
• Decreases mortality post MI
• Preserves renal function in diabetics
• Little effect on lipids/sexual function
• FETOTOXIC

Question 17

What are the 2 most common adverse effects of ACE inhibitors?

Answer 17

1) first dose HTN

2) Na+ depletion

Question 18

What are the other common adverse effects of ACE inhibitors?

Answer 18

• Dry cough
• Hyperkalemia
• Angioedema (allergic skin/mucosa disease)
• Renal insufficiency

Question 19

ARBs have basically the same effects of ACE inhibitors, except they do not have what side effect?

Answer 19

dry cough

Question 20

What are the side effects of ARBs?

Answer 20

• 1st does hypotension
• Hyperkalemia
• Hepatic dysfunciton
• Fetotoxicity
• Spruelike enteropathy (from olmesartan)

Question 21

Aliskiren has DDIs with what drugs?

Answer 21

drugs that inhibit p-glycoprotein (because aliskiren does too): erythromycin, amiodarone, etc.

Question 22

What are the mitogenic effects of angiotensin II that ACE inhibitors and ARBs inhibit?

Answer 22

1) Hypertrophy of cardiac myocytes
2) Hypertrophy of vascular SM
3) Cardiac and vascular fibrosis (remodeling)
4) Atherosclerosis

Question 23

Which drug has the phenomenon of aldosterone “escape”?

Answer 23

ACE inhibitors, over time, can no longer prevent the synthesis of aldosterone synthesis and this begins to increase

Question 24

When would you use an ARB over an ACE inhibitor?

Answer 24

if you cannot tolerote an ACE inhibitor (due to dry cough, etc.)

Question 25

Why were beta-blockers once contraindicated in CHF therapy?

Answer 25

becasue beta activation increases inotrophy needed when you have CHF

Question 26

Beta blockers mainly treat CHF by attenuating the deleterious effects of chronic high levels of what?

Answer 26

norepinephrine and epinephrine

Question 27

How do chronic high levels of NE and Epinephrine influence CHF?

Answer 27

- Beta receptor down regulation - Arrhythmias (cause of death in CHF) - Increased myocardial oxygen consumption (ischemia) - Myocyte apoptosis followed by fibrosis

Question 28

What are the short-term hemodynamic effects of beta blockers in CHF?

Answer 28

reduced CO and BP (may see initial worsening of symptoms before they get better)

Question 29

What are the long-term hemodynamic effects of beta blockers in CHF?

Answer 29

increased CO, decreased LVEDP

Question 30

When do you want to start beta blockers?

Answer 30

early in CHF to slow disease progression

Question 31

List the beta blockers approved for CHF treatment.

Answer 31

Metoprolol Crvedilol Bisoprolol

Question 32

What are the major molecular effects of beta blockers in CHF?

Answer 32

1) reverse desensitization of beta receptors 2) increase receptor number 3) restore fast signaling modes (contractility) over slow signaling modes (gene expression)

Question 33

What is unique about the chemical structure of digitalis?

Answer 33

CARDIAC GLYCOSIDE - Steroid nucleus - Unsaturated lactone ring - Glycoside residues

Question 34

What are the sources of digitalis?

Answer 34

plants and toad venom

Question 35

Why is digoxin almost exclusively used now?

Answer 35

- Convenient pharmacokinetics - Multiple ROA - Assay for measurements of serum levels

Question 36

What is the MOA of digoxin?

Answer 36

Increased intracellular availability of calcium for contractile apparatus via inhibition of sodium potassium pump (increase intracellular Na+. decrease intracellular K+)

Question 37

What does digoxin do to the pressure-volume curve?

Answer 37

shifts the curve upward and to the left

Question 38

Because digoxin is excreted unchanged by the kidney, how should you alter the dose in renal disease?

Answer 38

reduce it!

Question 39

How do you monitor the therapeutic action of digoxin?

Answer 39

plasma concentrations correlate roughly with theraapeutic effect and toxicity

Question 40

What are the adverse effects of digoxin?

Answer 40

- Atrial and ventricular arrhythmias - Visual changes (blurring, yellow-green halo) - Headache, fatigue, drowsiness, confusion, seizures

Question 41

How can you reverse the toxicity of digoxin?

Answer 41

Digibind (antibody to digoxin)

Question 42

List the DDIs of digoxin?

Answer 42

- Quinidine and Amiodarone increases plasma digoxin levels by decreasing elimination - Verapamil slow HR and digoxin toxicity - Diuretic can increase potential for arrhythmias due to hypokalemia

Question 43

Why does digoxin have so many DDIs?

Answer 43

it has a very narrow therapeutic window

Question 44

Long-term digoxin therapy may have what effect?

Answer 44

arrhythmias and worsened ventricular function

Question 45

What SYMPTOMS of CHF do diuretics treat?

Answer 45

promote Na+ and water excretion to reverse edema and pulmonary congestion

Question 46

Do diuretics really have an effect on CHF?

Answer 46

no, they just treat symptoms (reduce preload but do not increase CO)

Question 47

What 2 "high ceiling" diuretics are commonly used to treat CHF symptoms?

Answer 47

furosemide ("loop") | Bumetanide

Question 48

What is typically used in combination with loop diuretics?

Answer 48

potassium sparing diuretics (like aldosterone antagonists)

Question 49

What is an example of an aldosterone antagonist?

Answer 49

spironolactone

Question 50

What are the adverse effects of diuretics?

Answer 50

``` Electrolyte disturbances Hypokalemia Hyponatremia Metabolic alkalosis Dehydration, hypotension Ototoxicity (tinnitus and hearing loss from loop diuretics) ```

Question 51

What type of drugs reduce efficacy of diuretics by promoting fluid retention?

Answer 51

NSAIDs

Question 52

What drugs mimic the effects of diuretics but have a suboptimal effect that is not sufficient enough to prevent edema?

Answer 52

ACE inhibitors and ARBs by reducing sodium retention by preventing aldosterone release)

Question 53

What effects does spironolactone and eplerenone (aldosterone inhibitors) have other than diuretic effect?

Answer 53

Stop the direct mitogenic and fibrogenic effects of aldosterone (combined with AngII) on the myocardium that often leads to worsened LV function

Question 54

What effect do direct arterial vasodilators have in CHF? Name an example used in CHF.

Answer 54

reduce afterload to improve ventricular performance and increase CO. Hydralazine

Question 55

What must you combine with a arterial vasodilator to reduce both afterload and preload?

Answer 55

a venodilator (nitrate)

Question 56

When would you give a patient hydralazine?

Answer 56

only if they are unable to tolerate ACE inhibitors (ex. renal insufficiency or angioedema)

Question 57

What are the adverse effects of hydralazine?

Answer 57

nausea anorexia +FANA drug induced lupus (rare)

Question 58

How to nitrates reduce preload?

Answer 58

Veno and Vasodilation!! - Reduce pulmonary arterial pressure (pulmonary congestion) - Reduces left ventricular filling pressure and wall stress * these decrease preload and afterload

Question 59

Name the 2 IV inotropic agents.

Answer 59

dobutamine | milrinone

Question 60

What is the MOA of dobutamine.

Answer 60

Beta agonist and alpha agonist that vasodilates and serves as a "bridge" until the patient is stable enough for digoxin

Question 61

What drug should not be used with dobutamine?

Answer 61

beta-blocker therapy prevents the vasodilator effect of dobutamine and may actually cause vasoconstriction (from alpha 1 effect)

Question 62

What is a problem with dobutamine release?

Answer 62

desensitizaiton

Question 63

What drug works in the path of dobutamine but will not have the problem of desensitizaiton?

Answer 63

milrinone

Question 64

What is the MOA of milrinone?

Answer 64

PDE inhibitor to stop the breakdown of cAMP. This will lead to increased HR and increase contraction speed!

Question 65

When are ANP and BNP released from the atria and ventricles?

Answer 65

in response to volume/pressure expansion

Question 66

What are the levels of ANP and BNP like in CHF? Why?

Answer 66

they are naturally elevated to promote vasodilation, venodilation, and natriuresis

Question 67

What are the hemodynamic effects of ANP and BNP?

Answer 67

- Reduce preload - Inhibit renin/aldosterone release - Inhibits sodium reabsorption in proximal convoluted tubule - Selective afferent arteriolar vasodilation

Question 68

What is nesiritide? What is it approved for?

Answer 68

Nesiritide is recombinant human BNP approved for IV treatment of Class IV CHF

Question 69

What is the MOA of nesiritide?

Answer 69

- Binds to BNP receptor in vascular smooth muscle, increases cGMP to promote veno-and vasodilation: this reduces preload and afterload - Increases GFR by dilating renal arterioles, natriuresis (decreases Na resorption) - Suppresses R-A-A and SNS

Question 70

Who should be given nesiritide?

Answer 70

Class IV CHF in patients who do not respond to nitroglycerin

Question 71

BE SURE TO LOOK AT CHART!

Answer 71

Don't forget: BE SURE TO LOOK AT CHART!