Heart Failure Pharmacology

Question 1

goals of HF treatment

Answer 1

prevent patients from ever getting symptomatic HF

focus on stage A and B HF for prevention

once symptomatic, prevent hospitalization

prevent progression to stage D HF

Question 2

Stage A HF treatment

Answer 2

treat hypertension

encourage smoking cessation

treat lipid disorders

encourage regular exercise

discourage alcohol intake and illicit drug use

control metabolic syndrome

drugs: ACEI or ARB in appropritae patients

Question 3

Stage B HF treatment

Answer 3

all measure under A

drugs: ACEI or ARB as well as beta-blockers in appropriate patients

Question 4

Stage C HF treatment

Answer 4

all measures under stages A and B

dietary salt restriction

drugs for routine use: diuretics for fluid retention, ACEI, beta-blockers

drugs in selected patients: aldosterone antagonist, RBs, digitalis, hydralazine/nitrates

devices in selected patients: biventricular pacing, implantable defibrillators

Question 5

Stage D HF treatment

Answer 5

appropriate measures under stages A, B, or C

decide on appropriate level of care

options are end-of-life care/hospice

extraordinary measures include heart transplant, chronic inotropes, permanent mechanical support, experimental surgery or drugs

Question 6

symptoms of HF

Answer 6

low exercise capacity - decreased CO

dyspnea - pulmonary edema

orthopnea - increased venous return when supine

nocturia - increased venous return when supine

swelling, weight gain - salt and water retention

Question 7

signs of HF

Answer 7

increased JVP - elevated RA pressure

rales - pulmonary edema

S3 - elevated LV filling pressures and stiff LV

hepatomegaly - systemic venous congestion

edema - transudation of fluid from capillaries

Question 8

NYHA class I

Answer 8

no limitations of physical activity

Question 9

NYHA II

Answer 9

slight limitation of activity

dyspnea and fatigue with moderate physical activity

Question 10

NYHA III

Answer 10

marked limitation of activity

dyspnea with minimal activity

Question 11

NYHA IV

Answer 11

severe limitation of activity

symptoms are present at rest

Question 12

precipitating factors of HF

Answer 12

medication non-compliance

dietart indiscrtion

increased metabolic demands (fever, infection, anemia, tachycardia, hyperthyroidism, pregnancy)

increased circulating volume (increased preload)

increased afterload (uncontrolled systemic hypertension, pulmonary embolism)

reduced CO due to either reduced contractility or reduced stroke volume/abnormal heart rate

Question 13

principles of HF treatment

Answer 13

identify underlying etiology

eliminate precipitating cause

ameliorate HF symptoms

modulate maladaptive neurohormonal response

improve long-term survival

Question 14

steps to prevent heart failure

Answer 14

control blood pressure

control diabetes

control lipids

smoking cessation

weight control

early recognition and treatment of acute coronary syndromes

Question 15

treatment of symptomatic HF

Answer 15

identify and treat the underlying etiology of HF

eliminate precipitating factors

ameliorate HF symptoms

modulate maladaptive neurohormonal response

improve long-term survival

Question 16

treatment of heart failure with reduced EF (systolic HF)

Answer 16

improve Frank-Starling relationship in acute and asymptomatic patients

neurohormonal antagonists - reverse remodel and prolong life, pharmacogenomics is a possibility

devices to preevent sudden death

inotropic devices

heart replacement/support

Question 17

treatment of heart failure with preserved EF (diastolic HF)

Answer 17

so far randomized controlled trials have been disappointing

find and treat underlying etiology

agggressively treat hypertension

coronary revascularization

if atrial fibrillation - control rate and/or convert to normal sinus rhyth

treat comorbidities

Question 18

treatment of acute pulmonary edema in acute decompensated HF

Answer 18

LMNOP

L - loop diuretics, acutely venodilate and then natriuresis

M - morphine, venodilator to decrease sensation of dyspnea

N - nitrates, venodilator to increase pulmonary venous capacitance

O - oxygen, increased supply at a time when oxygen demand is high

P - positive pressure ventilation, improve oxygenation and decrease venous return, increases contractility

after acute stabilization, medicate underlying problem

Question 19

hemodynamic goals for achieving symptom relief and stabilization in acute decompensated EF

Answer 19

reduce right and left heart filling pressures

reduce systemic vascular resistance

increase cardiac output

Question 20

signs of congestion

Answer 20

orthopnea, increased JVP, rales, ascites, leg swelling

Question 21

signs of poor perfusion

Answer 21

cool extremities, decreased BP, decreased pulse pressure, sleepy/obtunded, worsening renal function, decreased urine output

Question 22

cold and wet

Answer 22

congested with poor perfusion

use vasodilators first and then inotropes

warm up and then diurese

Question 23

cold and dry

Answer 23

no congestion but poor perfusion

end-stage HF vasodilators, inotropes

LVAD

heart transplant

Question 24

warm and wet

Answer 24

congested but well-perfused

diurese and uptitrate HF meds

Question 25

warm and dry

Answer 25

reconsider HF diagnosis

Question 26

diuretics

Answer 26

most comonly used are secreted into the nephron via the proximal tubule (except aldosterone antagonists) therefore doses need to be increased in patients with chronic kidney disease categorized by site of action

Question 27

types of diuretics

Answer 27

proximal tubule - acetazolamide, rarely used thick ascending limb of loop of henle - loop diuretics distal convoluted tubule - thiazide diuretics collecting ducts - potassium-sparing diuretics

Question 28

loop diuretics

Answer 28

improve symptoms but increase neurohormones ex. furosemide, torsemide, bumetanide, ethycrinic acid (important, ototoxicity)

Question 29

thiazide diuretics

Answer 29

HCTZ, chlorthalidone, chlorhiazide, metolazone less potent than loop diuretics but can be very potent in combination

Question 30

potassium sparing diuretics

Answer 30

triamterene and amiloride rarely used aldosterone-antagonists, improve mortality

Question 31

deleterious effects of aldosterone

Answer 31

prothrombotic effects vascular inflammation and injury potassium and magnesium loss central hypertensive effects endothelial dysfunction ventricular arrhythmias cardiovascular disease sodium retention catecholamine potentiation myocardial fibrosis

Question 32

types of vasodilators

Answer 32

intravenous hydralazine nitrates ACE-inhibitors and angiotensin receptor blockers (ARBs)

Question 33

intravenous vasodilators

Answer 33

nitroglycerin nitroprusside nesiritide

Question 34

nitroglycerine

Answer 34

primarily a venodilator good for patients who are warm and wet but not patients who are cold because they can acutely worsen hypotension

Question 35

nitroprusside

Answer 35

mixed venous and arterial vasodilator vesodilator of choice if a patient is cold because it won't decrease preload as much as other agents

Question 36

nesiritide

Answer 36

recombinant BNP natriuretic peptide that also dilates veins and some arteries do not use in hypotensive patients because it may increase mortality or renal failure

Question 37

oral vasodilators

Answer 37

hydralazine nitrates ACE inhibitors ARBs

Question 38

hydralazine

Answer 38

pure arterial vasodilator reduces SVR, thereby increasing CO and can paradoxically increase BP

Question 39

nitrates

Answer 39

venodilator increased pulmonary venous capacitance, decreased pulmonary venous pressure, decreased hydrostatic pressure, decreased pulmonary edema use with caution in hypotensive patients who may be preload-dependent

Question 40

ACE inhibitors

Answer 40

block deleterious effects of angiotensin II increases bradykinin, which leads to vasodilation and cough

Question 41

angitensin receptor blocekrs (ARBs)

Answer 41

block angiotensin II receptor no cough, but no bradykinin-induced vasodilation better than ACE inhibitors because they block the receptor completely there is no cough, but benefits of high bradykinin is gone

Question 42

inotropes

Answer 42

all IV inotropes increase mortality in acute decompensated heart failure, so use with caution beta-adrenergic agonists phosphodiesterase inhibitors calcium sensitizers digitalis (digoxin)

Question 43

digoxin

Answer 43

decreases hospitalization but not mortality optimal concentration between 0.5 and 0.8 ng/ml higher dizes increases mortality blocks Na/K-ATPase which increases calcium in the cell due to the sodium/calcium pump adrenergic modulation

Question 44

beta-blockers

Answer 44

indicated for all classes of systolic HF use after stabilization of the patient, can cause acute decompensation, so start low and be cautious if a patient is on chronic beta-blocker therapy and gets admitted for ADHF, try to keep on beta-blocker if possible reduce mortality

Question 45

beta-adrenergic agonists

Answer 45

ex. dobutamine, dopamine, and norepinephrine can cause increased contractility, increaed HR, peripheral vasodilation, and peripheral vasoconstriction depending on the drug **dobutamine** is most commonly used

Question 46

phosphodiesterase inhibitors

Answer 46

amrinon and milrinone milrinone is the only one clinically used these work intracellularly and bypass the beta-receptor by increasing cAMP also increase contractility and cause peripheral vasodilation

Question 47

calcium sensitizers

Answer 47

levosimendan sensitizes myocytes to calcium, which increases contractile force no evidence of outcome benefits

Question 48

limitation of drugs in heart failure

Answer 48

too many need to be taken without specified periodicity side effects/toxicity drug/drug interactions costly

Question 49

non-pharmacologic therapies

Answer 49

**lifestyle / dietary chagnes / exercise** **treatment of comorbidities** **ultrafiltration** - alternative to diuretic therapy **cadiac resynchronizatino therapy (CRT)** **implantable cardiac defibrillator (ICD) therapy** - used in patients in class I-III HF but not patients with class IV **surgical therapies** - mitral valve repair, ventricular assist device, cardiac transplantation

Question 50

cardiac resynchronization therapy (CRT)

Answer 50

indicated in symptomatic patiwhts with NYHA class III or IV with persistent symptoms despite optimal medical management patients who most likely have intraventricular and interventricular electrical and mechanical dyssynchony by pacing RV and LV simultaneously, cardiac function can improve in these patietns

Question 51

ventricular dyssynchrony

Answer 51

uncoordinated electrical and mechanical contraction of the ventricles may involve disruption of collagen matrix - impairs electrical condcution and mechanical contraction or efficiency associated with woprse prognosis and impaired hemodynamic function