Drugs to treat HF Flashcards
HF can occur under which conditions
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
NYHA Stage I HF
only at levels of exertion that would limit normal individuals
NYHA Stage II HF
symptoms on ordinary exertion
NYHA Stage III HF
symp on less than ordinary exertion
NYHA Stage IV HF
symptoms at rest
Systolic dysfunction versus diastolic dysfunction
systolic: difficulty in Ca entering cell, abnormally weak contraction during systole
diastole- abnormal relaxation, diff in Ca+ sequestration
signs and symptoms of HF
- 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.
abnormal baroreflex control in HF
- 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
cardiac hypertrophy
hypertrophied heart operates at lower inotropic state
-adaptation mech
alt renal fxn in HF
adaptation
SNS induced vasoconstriction shunts blood from glomeruli and stim renin release, leads to Na retention, increased blood volume, edema
vasoconstriction in HF
SNS, RAS, ADH all react to sustain arterial pressure with the low CO accompanying HF by increasing PVR
edema in HF
increased venous pressure leads to decreased fluid returning to capillaries on the venous side of the capillary beds
first rx of HF
-correct any reversible causes: arrhythmias, HTN, surgical rx of valve, rx anemia, thyrotoxicosis, other causes of high CO HF
AHA stage A & rx
- 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
AHA stage B & rx
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
AHA stage C & rx
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
AHA Stage D & rx
- 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
only drugs used in rx of HF that reduce mortality when used alone:
ACEI, ARB, B blockers
ACEI in HF
- 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
ARB in HF
- 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
diuretics in HF
- 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
B blockers in HF
-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
digoxin
-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
aldosterone antagonists in HF
- 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
isosorbide dinitrate
- 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
hydralazine
- 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
sodium nitroprusside
IV vasodilator, NO source that reduces both vent filling pressure and SVR
-used for decomp HF
nitroglycerine
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
dopamine in HF
- 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
dobutamine in HF
- 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
amrinone
- 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
- 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
