Drugs to treat HF

Question 1

HF can occur under which conditions

Answer 1

when there is a high metabolic demand of the tissues (may not have a dec EF bc of compensation)

• hyperthyroidism
• beriberi
• anemia
• major AV shunts

Question 2

NYHA Stage I HF

Answer 2

only at levels of exertion that would limit normal individuals

Question 3

NYHA Stage II HF

Answer 3

symptoms on ordinary exertion

Question 4

NYHA Stage III HF

Answer 4

symp on less than ordinary exertion

Question 5

NYHA Stage IV HF

Answer 5

symptoms at rest

Question 6

Systolic dysfunction versus diastolic dysfunction

Answer 6

systolic: difficulty in Ca entering cell, abnormally weak contraction during systole
diastole- abnormal relaxation, diff in Ca+ sequestration

Question 7

signs and symptoms of HF

Answer 7

• hemodynamic abnormalities
• dysregulation of Ca homeostasis resulting in prolonged Ca transient due to reduction of Ca sequestration by SERCA and Ca uptake by Na/Ca exchanger (if impaired uptake by SERCA, less Ca available for next cycle bc pumped out of cell by NCX)
• dysregulated expression of contractile PRO interferes w cross bridge cycling
• desensitization of B adrenergic receptor Gs p’way. receptor down regulation and inactivation by B adrenergic receptor kinase, which ultimately leads to reduced Ca uptake into SR
• cardiomyocytes are lost by cell death, structure maintained by fibroblast like cells called myofibroblasts. pathological remodeling
• energy delivery, prod and storage and energy utilization are not directly involved.

Question 8

abnormal baroreflex control in HF

Answer 8

• adaptation mechanism
• reduced fxn of both arterial and venous baroreceptors leads to increased activity of SNS, RAS, vasopressin; receptors interpret HTN as normal, fail to inhibit SNS

Question 9

cardiac hypertrophy

Answer 9

hypertrophied heart operates at lower inotropic state

-adaptation mech

Question 10

alt renal fxn in HF

Answer 10

adaptation
SNS induced vasoconstriction shunts blood from glomeruli and stim renin release, leads to Na retention, increased blood volume, edema

Question 11

vasoconstriction in HF

Answer 11

SNS, RAS, ADH all react to sustain arterial pressure with the low CO accompanying HF by increasing PVR

Question 12

edema in HF

Answer 12

increased venous pressure leads to decreased fluid returning to capillaries on the venous side of the capillary beds

Question 13

first rx of HF

Answer 13

-correct any reversible causes: arrhythmias, HTN, surgical rx of valve, rx anemia, thyrotoxicosis, other causes of high CO HF

Question 14

AHA stage A & rx

Answer 14

• at risk for HF, but no structural disease or symptoms
• HTN, atherosclerosis, diabetes, obesity, cardiotoxins, family hx
• rx hypertension, dyslipidemia, encourage cessation of smoking, ETOH, and illicit drug use
• ACE or ARB

Question 15

AHA stage B & rx

Answer 15

structural heart disease but no s/s

• pt w prior MI, ventricular remodeling, asymptomatic vascular disease
  rx: all under stage A
• ACE/ARB, B blocker

Question 16

AHA stage C & rx

Answer 16

structural heart disease w prior or current symp of HF
-pt w known structural HD, dyspnea, fatigue, reduced exercise tolerance
-Rx: all stage A & B + salt restriction
* diuretics if edematous, ACEI, B blockers
for some: aldosterone antagonists, digitalis, hydralazine/nitrates

Question 17

AHA Stage D & rx

Answer 17

• refractory HF
• symptoms at rest despite therapy who are recurrently hospitalized
  rx: A, B, C
• EOL care/hospice
• extraordinary measures, heart transplant, chronic inotropes, mech support, experimental surgery/drugs

Question 18

only drugs used in rx of HF that reduce mortality when used alone:

Answer 18

ACEI, ARB, B blockers

Question 19

ACEI in HF

Answer 19

• first line therapy
• should be prescribed to all pt w HF w reduce LVEF
• often used in combo w B blocker
• improve survival in patients with HF and systolic vent dysfxn, 40% reduction in mortality over 6 months
• survival benefit in pt with mild-mod HF
• prevent progression of HF in pt after MI

Question 20

ARB in HF

Answer 20

• ACEI remian first choice for inhibition of the RAS in CHF but ARB are reasonable alt
• comparable mortality benefits to ACEI
• no benefit to combo of ACEI and ARB

Question 21

diuretics in HF

Answer 21

• interfere with the sodium retention of HF in hibiting the reasborption of the Na or Cl at sites in the renal tubules
• loop diuretics are preferred in most patients with HF, although thiazides may be preferred with HTN patients
• produce symptomatic benefits more rapidly than any other drug for HF
• should not be used along in patients w stage C HF
• no mortality benefit in HF

Question 22

B blockers in HF

Answer 22

-MOA not fully elucidated, anti arrhythmic benefit by impairing SNS mediated increases in automaticity and hypokalemia
-improved LV structure and fxn by preventing remodeling of the heart
-improvement of abnormal Ca handling in HF by preventing hyperphosphorylation of RyR which causes diastolic leak of Ca from SR
-B blockers should be rx to all pt with HF due to reduced LVEF unless contraindicated (asthma, bradycardia)
3 agents reduce death (bisoprolol and metoprolol (B1 selective) and carvedilol (alpha 1 , B1, B2)
-reduced heath from HF

Question 23

digoxin

Answer 23

-naturally occurring steroid that was a mainstay of HF rx until ACEI and B blockers bcm popular
-benefits are now believed to be due in part of effects on non-cardiac tissues, in sympathetic nerves and kidney
-increases the force of cardiac contraction by increasing intracellular free Ca y inhibiting Na/K ATP ase. Increased CO decreases reflex SNS activity and increases renal perfusion
-sensitizes cardiac baroreceptors (sense Pa as higher), digoxin increases vagal tone by actions on vagal afferents and by increasing SA nodal cell sensitivity to Ach. (dec SNS, inc PNS)
-inhibit NA/K ATPase in kidney, reduces renal tubular reabs of Na, increases Na delivty to the distal tubules, reduces renin release
-considered for use in pt w HF who are in Afib or with persistent or severe symp of HF despite therapy w diuretics, ACEI/ARB, B blockers
Risks: roxicity r/t electrical pop of heart (narrow TI)
-levels of dig in the therapeutic range may have deleterious effects on heart with LT use
-tox can be rx with anti-dig immunotherapy
-no effect on survival

Question 24

aldosterone antagonists in HF

Answer 24

• ST therapy with both ACEI/ARB can lower circulating aldosterone, cannot be sustained with LT treatment
• aldosterone exerts adverse effects on the structure/fxn of heart, independetly of and in addition of deleterious effects prod by Ang II
• addition of aldosterone antag should be considered in pt with moderately severe HF or w L vent dysfxn after MI
• drugs should not be given without concomitant diuretic therapy
• class III/IV: low doses of spironolactone reduced mort

Question 25

isosorbide dinitrate

Answer 25

• venodilation
• increases venous capacitance and reduces preload
• increases coronary artery flow by vasodilation, which may enhance vent fxn
• less effective as arteriodilator, limits use as monotherapy. often used in combo w hydralazine

Question 26

hydralazine

Answer 26

• arterial vasodilator with little effect on venous tone
• effective in reducing renal vascular resistance and increasing renal BF, so can be used in pt who cannot tolerate ACEI
• used in combo w isosorbide dinitrate and available as combo
• may provide HD improvement in pt with adv HF being rx w ACEI, dig, diuretics
• hydralazine/isosorbide together increase survival, but not as effectively as ACEI

Question 27

sodium nitroprusside

Answer 27

IV vasodilator, NO source that reduces both vent filling pressure and SVR
-used for decomp HF

Question 28

nitroglycerine

Answer 28

NO source relatively selective for venous capacitance vessels. indicated for rx of L HF d/t MI or when prompt reduction of vent filling pressure is needed

Question 29

dopamine in HF

Answer 29

• Stim B adren receptors to stim cardiac contractility at intermediate infusion
• stim alpha at high inf rates, to stim peripheral arterial and venous constriction, which may be desirable to support critically reduced Pa in circulatory failure, but does not help HF
• tachycardia can provoke ischemia in patients with CAD

Question 30

dobutamine in HF

Answer 30

• B agonist of choice for pt with systolic dysfunction and congestion assoc with HF. stim B1 and B2 receptors for inotropic effect. increase in renal BF is proportional to increase in CO
• can be infused for several days, but tolerance limits efficacy with LT use.
• SE: tachycardia, arrhythmia –> dose reduction

Question 31

amrinone

Answer 31

• stimulate myocardiac contraction and accelerate relaxation by inc cAMP by preventing its degredation. cAMP activates PKA, resulting in increased Ca entry, increased SR Ca uptake, and increased SR Ca release (CICR).
• stimulated balanced arterial and venous dilation
• CO increases by stimulated contractility and decreased LV afterload

Question 32

milrinone

Answer 32

• stimulate myocardiac contraction and accelerate relaxation by inc cAMP by preventing its degredation. cAMP activates PKA, resulting in increased Ca entry, increased SR Ca uptake, and increased SR Ca release (CICR).
• stimulated balanced arterial and venous dilation
• CO increases by stimulated contractility and decreased LV afterload
• milrinone has more favorable SE profile, shorter t1/2, more selective for PDE3