Drugs for Treatment of Heart Failure Lecture PDF

Question 1

Types of heart lesions that can facilitate the vicious cycle of heart failure (5)

Answer 1

• ischemia
• infarction
• myopathy
• hypertension
• valve disease

Question 2

Vicious cycle of heart failure mech of action

Answer 2

• Cardiac lesion decreases cardiac performance
• Baroreceptor fails to be stimulated resulting in increased sympathetic response
• vasomotor response to constrict to increase pressure to perfuse various organs of the body
• Kidney’s juxtaglomerular cells activates RAAS system which causes vasoconstriction and fluid retention (aldosterone)
• workload of heart is increased (afterload and preload)
• increased workload causes myocardial cell structural damage
• further impaired decreased cardiac performance dropping cardiac output even more
• this stimulates causes failure to stimulate baroreceptors….

Question 3

Drug classes for management of heart failure (4)

Answer 3

• B blockers
• ACE inhibitors
• aldosterone antagonists
• diuretics

Question 4

2 natriuretic peptides released by heart and their function

Answer 4

1) Atral natriuretic peptide - released in response to increased stretching of atrium to promote loss of Na+ and H2O into urine
2) B natriuretic peptide - Released in response to increases stretching of ventricles and promote arterial and venous dilation and increase GFR to kidney resulting in decreased systemic resistance and loss of Na+ and H2O in urine

Question 5

Natriuretic peptides are beneficial in ____

Answer 5

diagnosis of heart failure

Question 6

Why are ACEI preferred to ARB’s in HF

Answer 6

ACEI increase levels of bradykinin which also help in vasodilation and reducing pressure making them HIGHLY efficacious agents, despite the side effect of cough

Question 7

Drug treatment clinical outcomes in patients with heart failure with preserved ejection fraction

Answer 7

-little evidence it improves clinical outcomes beyond relief

Question 8

3 routine therapies for heart failure and how they impact the condition

Answer 8

• diuretics (decrease preload, afterload, pulmonary edema, cardiac distension)
• RAAS inhibitors (promote dilation of artereioles and veins and decrease aldosterone release)
• B blockers (not understood mechanism)

Question 9

DOC for patients with severe heart failure and why

Answer 9

Loop diuretics (furosemide), promote strong diuresis and work even when GFR is low

Question 10

Unless contraindicated, all patients with HFrEF should receive what drug class for treatment?

Answer 10

ACEI

Question 11

3 major benefits of ARB’s

Answer 11

• promote dilation of arterioles
• promote dilation of veins
• decrease release of aldosterone

Question 12

ARB’s 4 effects in heart failure, but why are they not preferred?

Answer 12

• improve LV ejection fraction
• reduce heart failure symptoms
• increase exercise tolerance
• reduce mortality

Do not increase kinin levels having less favorable impact on cardiac remodeling than ACEI

Question 13

sacubitril/valsartan (entresto) drug class, function, and mech of action

Answer 13

• Angiotensin receptor neprilysin inhibitor (ARNI)
• approved for patients with class II-IV HF to be used in place of an ACEI or ARB as it is superior than elanapril alone when looking at reduced risk of CV related death
• functionally increases natriuretic peptide levels by inhibiting neprilysin that breaks them down

Question 14

sacubitril/valsartan (entresto) ADR’s (4)

Answer 14

• hypotension by volume depletion
• cough
• hyperkalemia
• fetal harm

Question 15

Aliskiren (tekturna) function

Answer 15

Can shut down RAAS by binding renin, should work as well as ACEI and ARB’s but is only approved for HTN and not for treatment of HF (doesn’t improve outcomes)

Question 16

Aldosterone antagonists functions (2) and two examples

Answer 16

• Block receptors for aldosterone in heart and blood vessels, can prevent myocardial remodeling and delay fibrosis (aldosterone increases fibrosis of myocardium and vascular) (as well as its original function to prevent Na+ and thus H2O retention with K+ excretion)
• spironolactone and eplerenone

Question 17

To avoid the endocrine effects of spironolactone, it is preferable to use the equivalent…

Answer 17

…eplerenone (inspra)

Question 18

B-blockers indication and 3 uses in HF

Answer 18

Used in patients class II-IV HF, thru unknown mechanism -can increase LV ejection fraction

• prevent progressive enlargement
• decrease intracardiac and pulmonary vascular pressures over 1-3 months

Question 19

B blockers ADR’s (4)

Answer 19

• caution in patients with asthma or severe bradycardia
• fluid retention
• fatigue
• hypotension (need to start at low dose)

Question 20

Ivabradine (Corlanor) drug class and indications

Answer 20

• SA node inhibitor (selective for funny channels slowing firing of SA node and reducing HR)
• indicated for patients with resting HR of at least 70bpm and are on max doses of B blockers or have contraindications of it, and have and LVEF equal or less than 35%

Question 21

Ivabradine (Corlanor) mech of action

Answer 21

-causes dose dependent reduction in HR by blocking channels responsible for cardiac pacemaker current, does not affect BP

Question 22

Ivabradine (Corlanor) ADR’s (3) and contraindications (3)

Answer 22

• Bradycardia
• hypertension
• afib
• Low BP
• sick sinus syndrome
• 3rd degree heart block

Question 23

Sympathomimetic and PDE inhibitors function

Answer 23

IV drugs for treatment of acute heart failure when vasodilator drugs are not effective in restoring hemodynamics

Question 24

Dopamine (inocor) function at diff doses

Answer 24

Low - stimulate kidneys
Intermediate - increase inotropy and thus SV/CO
Large - stimulates a1 receptors on vascular smooth muscle producing vasoconstriction

Question 25

Dobutamine function

Answer 25

Catecholamine with selective activation of B1 adrenergic receptors not acting on a1 receptors and thus does not increase vascular resistance, preferred for short term treatment of acute HF by IV

Question 26

Amrinone (Inocor) drug class and function

Answer 26

- Phosphodiesterase inhibitor - Short term treatment of HF by increasing cAMP activity creating a pos inotropic effect refractory to digoxin, diuretics, and vasodilators

Question 27

Isosorbide dinitrate plus hydralazine (ISDN) drug class and function

Answer 27

- Vasodilator - Used for treatment of HF, used to dilate veins, release nitric oxide, and cause relaxation of vascular smooth muscle in severe refractory HF to reduce congestion

Question 28

Isosorbide dinitrate plus hydralazine (ISDN) drug interaction

Answer 28

-should not be taken with phosphodiesterase inhibitors such as sildenafil

Question 29

Hydralazine function

Answer 29

Adjunct treatment for CHF in combo with ISDN allowing for vasodilation improving CO and renal blood flow

Question 30

BiDil (Nitromed) function

Answer 30

Fixed dose combo of ISDN that is approved for adjunctive use in treatment of heart failure in black patients

Question 31

Nitroglycerin function

Answer 31

Potent venodilator causing a dramatic decrease in preload on the heart, in HF used to reduce acute severe pulmonary edema but should not be taken with PDE5 inhibitors such as sildenafil

Question 32

Sodium nitroprusside (nitropress) function

Answer 32

Agent to rapidly dilate arterioles and veins for short term therapy of severe HF

Question 33

Nesiritide (natrecor) function

Answer 33

Synthetic form of BNP used in short term IV treatment, dilates both veins and arterioles reducing pre and afterload

Question 34

Digoxin (lanoxin, loxicaps) drug class and function

Answer 34

- Old school family of drugs known as cardiac glycosides - indicated for HF and control of arrhythmias derived from purple foxglove plant, does NOT prolong life despite reducing symptoms by increasing contractility and exercise tolerance

Question 35

Digoxin (lanoxin, loxicaps) mech of action

Answer 35

- accelerates entry of Ca2+ into cardiac muscle cells - during AP, Na+ and Ca2+ enter cardiac muscle cells and K+ exits - Then Na/K ATPase pumps things back and Ca2+ leaves via Na/Ca transporter - Inhibits adenosine triphophate (ATPase which energizes Na+/K+ pump - buildup stimulates exchane of Na for Ca2+, increasing levels in cell - greater contraction - too much K+ will inhibit effect of digoxin

Question 36

What must be monitored and kept in normal range when on digoxin?

Answer 36

K+

Question 37

Beneficial effects of digoxin (3)

Answer 37

- decrease sympathetic tone (more complete ventricular filling) - increased urine output - decreased renin release - electrical effects on heart

Question 38

Efficacy of digoxin in HF depends on...

Answer 38

...cardiac reserve, if heart is too sick there will be minimal effects

Question 39

Digoxin electric effects

Answer 39

- inhibit Na+/K ATPase - enhance vagal influences on heart - increase automaticity potentially generating ectopic foci resulting in ventricular arrhythmias - AV block with escape beats***

Question 40

Most common cause of arrhythmias

Answer 40

Hypokalemia secondary to diuretic use

Question 41

Diagnosis of cardiotoxicity in digoxin administration

Answer 41

-very complex, unknown if arrhythmia caused by digoxin or disease process, resolution upon withdrawal confirms diagnosis

Question 42

Drug for patients with bradycardia or AV block due to digoxin toxicity and why

Answer 42

Atropine - it is an anticholinergic that inhibits parasympathetic action on the heart, therefore reversing some of the effect of digoxin toxicity via a separate mechanism

Question 43

Digoxin dosing

Answer 43

Use ng/ml opposed to mg