ch 48 pg 529-545 Drugs for HF Flashcards
What are the two major forms of HF
- Heart failure with left ventricular (LV) systolic dysfunction (aka HF with reduced LV ejection fraction; HFrEF)
- diastolic HF (aka heart failure with preserved LV ejection fraction; HFpEF)
for these, the first form is mainly what HF refers to
WHat is heart failure
progressive, often fatal disorder characterize by ventricular dysfunction, reduced CO, insufficient tissue perfusion, and signs of fluid retention (peripheral edema, SOB etc)
What type of drugs recommended for treating HF
Diuretics, inhibitors of the RAAS, beta blockers, digoxin
Patho of HF
-heart is unable to pump sufficient blood to meet the metabolic needs of tissues
-characterized by signs of inadequate tissue perfusion (fatigue, SOB, exercise intolerancce), and/or signs of volume overload (venous distention, peripheral & pulmonary edema)
-underlyding causes= chronic hypertension & myocardial infarction (others include valvular heart disease, coronary artery disase, congestial heart disease, dysrhythmias, aging of the myocardium)
-early stages= HF is asymptomatic. as progresses, fatigue & SOB develop. As cardiac performance declines further, blood backs up behind the failing ventricles causing venous distention, peripheral edema, and pulmonary edema
Cardiac remodelling
inital phase of HF–> heart undergoes remodelling (ventricles dilate, hypertrophy (increase in wall thickness), and become more spherical)
-increases wall stress and reduce LV ejection fraction
-remodelling occurs in response to cardiac injury brought on by infarction and other causes
-process is driven primarily by neurohormonal systems (SNS, RAAS)
Physiologic Adaptations to Reduced CO
Cardiac Dilation
-Results from a combination of increased venous pressure and reduced contractile force
(reduced contractility lowers the amount of blood ejected during systole, causing end-systolic volume to rise. the increase in venous pressure increases diastolic filling which causes heart to expand even further)
-Because of starlings mechanism, the increase in heart size that occurs in HF helps improve CO. As the heart fails and its volume expands, contractile force increases, causing a corresponding increas in stroke volume. the maximal contractile force that can be developed by the failing heart is considerably lower than the maximal force of the healthy heart
Increased Sympathetic tone
-HF causes arterial pressure to fall; in response, the baroreceptor reflex increases sympathetic output to the heart, veins, and arterioles. at the same time the Parasympathetic effects on the heart are reduced
–>increased HR; if increases too much. there will be insufficient time for complete ventricular filling, and CO will fail
–> increased contractility; will actually cause increased oxygen demand
–>increased venous tone; will increase venous pressure and thereby increase ventricular filling. Starlings mechanism will result in increased stroke volume–> if pressure is excessive, blood will back up behind the failing ventricles
–>* increased arteriolar tone*; increases arterial pressure, thereby inreasing perfusion of vital organs. unfortunately, increased arterial pressure also means the heart must pump against greater resistance
Water Retention and Increased Blood Volume
mechanisms:
1. reduced CO causes reduction in renal blood flow, decreasing GFR–> urine production is decreased and water is retained. retention of H20 increases blood volume
2. HF activates the RAAS
Natriuretic peptides
-in response to stretching of the atria and dilation of the ventricles, the heart releases 2 natriuretic peptides; artial natriuretic peptide (ANP) and B-natriuretic peptide (BNP)
-these hormones promote filation of arterioles and veins, and also promote a loss of sodium and water through the kidneys. hence they tend to counterbalance vasoconstriction caused by the SNS and angiotension 2, as well as retention of sodium and water caused by the RAAS
-high levels of BNP indicate poor cardiac health and can predict a lower chance of survivial
Vicious cycle of “compensatory” physiologic responses
(1)cardiac dilation (2)activation of SNS (3)Activation of RAAS (4)rentention of water and sodium
-excessive HR can reduce ventricular filling; excessive arterial pressure can lower CO; excessive venous pressure can cause pulmonary & peripheral edema
-the compensatory responses can create a self-sustaining cycle of maladaption that further impairs CO and tissue perfusion
S&S of HF
-prominent S&S are direct consequence of the pathophysiology just described
-decreased tissue perfusion results in** reduced exercise tolerance, fatigue, and SOB**
-SOB may also reflect pulmonary edema
-increased sympathetic tone produces tachycardia
-increased ventricular filling, reduced systolic ejection, and myocardial hypertrophy result in cardiomegaly (increased heart size)
-weight gain results from fluid retention
-the combination of increased venous tone plus increased blood volume helps cause pulmonary edema, peripheral edema, hepatomegaly (increased liver size), and distention of the jugular veins
Classification of HF Severity
Drugs used to treat HR- Diuretics
diuretics are 1st line for all patients with signs of volume overload. By reducing blood volume, these drugs can decrease venous pressure, arterial pressure (afterload), pulmonary edema, peripheral edema, and cardiac dilation. for the most part, benefits of diuretics are limited to symptom reduction
Thiazide diuretics
- eg= hydrochlorothiaizde
- produce moderate diuresis
- used for long term therapy of HF when edema is not too great
- since thiazides are ineffective when GFR is low, these drugs cannot be used if CO is greatly reduced
- adverse effect= hypokalemia, which incresed the risk of digoxin-induced dysrhythmias
Loop Diuretics
- eg= furosemide
- produce profound diuresis
- promote fluid loss even when GFR is low
- preferred to thiazides when cardiac output is greatly reduced
- oral or IV
- drug of choice for patients with severe HF
- can cause hypokalemia, increasing risk of digocin toxicity
- can cause severe hypotension secondary to excessive volume reduction
Potassium-Sparing Diuretics
- eg. spironolactone, triamterene
- only produce scant diuresis
- in pts with HF, these drugs are employed to countract potassium loss caused by thiazide and loop diuretics, thereby lowering the risk of digoxin-induced dysrhythmias
- adverse effect= hyperkalemia
- spironolactone prolongs survival in pts with HF primarily by blocking receptors for aldosterone, not by causing diuresis
Drugs used to treat HF- Drugs that inhibit the RAAS
five groups of drugs that inhibit the RAAS:
1. ACE inhibitors (Captopril)
2. ARBs (Losartan)
3. Angiotensin receptor neprilysin inhibitors (ARNIs) (Entresto)
4. direct renin inhibitor (DRIs)
5. aldosterone antagonists (eplerenone)
ACE inhibitors have been studied the most thoroughly in HF
ACE inhibitors
eg= captopril, enalapril
-improves functional status and prolongs life
-block the production of angiotensin II, decreasing the release of aldosterone, and suppressing the degradation of kinins
ACE inhibitors Hemodynamic Benefits
-Arteriolar Dilation: improves regional blood flow in the kidneys and other issues. by reducing afterload, it increases stroke volume and CO. increased renal blood flow promotes excretion of Na and H20
-Venous Dilation: reduces venous pressure and thereby reduces pulmonary congestion, peripheral edema, preload, and cardiac dilation
-Suppression of Aldosterone Release: enhances excretion of Na and H20, while causing retention of potassium
Ace inhibitors impact on cardiac remodelling
favorable impact on cardiac remodelling- elevation of kinins is largely responsible
ACE inhibitors adverse effects
hypotension (2ndary to arteriolar dilation), hyperkalemia (2ndary to decreased aldosterone release), intractable cough, angioedema
can cause fetal injury
