Pharm - Heart Failure Flashcards
ACC/AHA and NYHA classification
She said she wouldn’t test over this - review just to get general idea
Goals of therapy for HFrEF
- reduce morbidity
- reduce mortality
reducing morbidity in therapy of HFrEF
- reducing symptoms
- improving sx can be achieved by putting pts on:
- diuretics
- beta blockers
- ACEIs
- ARBs
- ARNIs
- hydralazine + nitrate
- dig
- aldosterone antagonists
- improve quality of life and functional status
- decrease rate of hospitalization
reducing mortality in therapy of HFrEF
- pt survival has been prolonged w/ use of:
- beta blockers
- ACEis
- ARNIs
- hydralazine + nitrate
- aldosterone antagonists
What is the goal of drug treatment for HFrEF?
- improve sx
- slow or reverse deterioration in myocardial function
- reduce mortality
specific drug treatment for HFrEF
-all treated w/ ACEi or ARB and beta blocker!!
ACEIs
- lisinopril
- ramipril
- quinapril
- fosinopril
- enalapril
ARBs
- losartan
- valsartan
- candesartan
beta blockers
- carvedilol
- metoprolol ER
- bisoprolol
neprilysin/ARB
sacubritril/valsartan (entresto)
for all volume overloaded pts, what drug do you add?
loop diuretic
for persistently symptomatic african americans add what drug?
hydralazine-nitrates
if creatinine clearance is >30 mL/min and serum potassium <5.0 mEq/dl add what drug?
aldosterone antagonist: (spironlactone, eplerenone)
be able to…
ID meds missing from a med list for a pt with HFrEF
loop diuretics mechanism of action
-inhibit reabsorption of Na and Cl in the ascending loop of Henle and distal renal tubule leading to an increased excretion of water, Na, Cl, Mg, and Ca
the diuretic response of the kidney to a loop diuretic is dependent upon what?
- how much diuretic reaches the site of action
- it is a threshold type dose-response curve
why do people w/ HF have a reduced response to a diuretic?
- decreased delivery of diuretic to kidney b/c renal blood flow is reduced
- increased Na reabsorption at other sites d/t RAAS and SNS
- delayed intestinal reabsorption d/t gut edema
indication for loop diuretics HFrEF
- only drugs used for tx of HF that can adequately control fluid retention of HF
- prescribe to all pts who have evidence of fluid retention
contraindications to loop diuretics
- hypersensitivity
- anuria
loop diuretics monitoring parameters
- weight
- resolution of sx: pulm. congestion, peripheral edema, elevated jugular venous pressure
- serum potassium (very important)
patient factors that may lead to diuretic resistance
- significant impairment of renal fxn/perfusion
- increase in Na-retaining hormones (AII and aldosterone)
- hypoalbuminemia
- consuming lg amounts of dietary Na
- taking agents that can block effects of diuretics: NSAIDs
why does hypoalbuminemia cause diuretic resistance?
- all diuretics are highly protein bound which limits them to the vascular space and ensures better delivery of drug to kidneys
- reduced albumin = less protein binding of diuretic
- more “free” diuretic to move into extravascular space
how can diuretic resistance be overcome?
- IV admin of diuretics by intermittent bolus therapy or continuous IV infusions
- switch from oral furosemide to torsemide or bumetanide
- add diuretic w/ different MoA (thaizide)
- for pts w/ systolic HF, add spironolactone or eplerenone
ADRs for loop diuretics
- electrolyte and fluid depletion
- hypotension and azotemia
- depeletion of K and Mg can predispose pts to serious cardiac arrhythmias (higher risk when using 2 diuretics)
- hyperuricemia
- photosensitivity
positive patient outcomes when using an ACEI to treat HFrEF
- lead to symptomatic improvement
- reduce hospitalization
- enhance survival
ACEI MoA
- not completely understood
- she said she wouldn’t test on this, just have general understanding
contraindications for ACEIs
- if they have experienced life-threatening adverse rxns during previous exposure
- pregnant or plan to become pregnant
prescribe ACEI with CAUTION if pt has 1 or more of the following:
- symptomatic or very low systemic BP
- marketdly increased serum levels of creatinine (>3 mg/dL)
- b/l renal artery stenosis
- elevated levels of serum K (>5 mEq/L)
describe the prescribing pattern when initiating an ACEI and beta-blocker for a pt w/ HFrEF
- ACEI benefit is a class effect
- ACEIs are used w/ beta blockers
- ACEI is initiated 1st and titrated to moderate dose
- then beta blocker is titrated to max dose, followed by uptitration of the ACEI to max tolerated dose
- begin at low doses and advance as tolerated
ACEI monitoring parameters
- assess renal fxn and serum K w/i 1 week and 1 month of initiation and periodically thereafter
- abrupt withdrawal of treatment can lead to clinical deterioration and should be avoided
mechanism of ACEI induced cough
- not fully known
- increased local concentrations of kinins, substance P, prostaglandins, or thromboxane may be involved
- kinins and substance P are metabolized by ACE so their levels are increased by ACEI
what is the most appropriate tx for ACEI induced cough
- improvement begins w/i 4-7 days after ACEI is dc
- re-admin of an ACEI is associated w/ high occurrence rate
- pts w/ good antihypertensive response to ACEI can be switched to ARB (lower rate of cough)
What is the mechanism of ACEI induced hyperkalemia
- ACEIs block release of aldosterone through blocking AII
- this impairs efficiency of urinary K excretion
- generally raise the serum K by less than .5 meq/L in pts w/ normal renal fxn
more prominent hyperkalemia may be seen in pts with:
- renal insufficiency
- DM
- concurrent use of a drug promoting K retention such as K-sparing diuretic
- concurrent use of a nonsteroidal anti-inflammatory drug
- elderly
explain the mechanism of ACEI induced renal impairment
- GFR is maintained in part by AII-induced increase in resistance at efferent arteriole
- blocking it w/ ACEI will sequentially relax the efferent arteriole, lower intraglomerular pressure and reduce GFR
what is the clinical effect of a pt w/ renal impairment secondary to an ACEI
- rise in serum creatinine concentration generally begins a few days after starting ACEI
- renal fxn should be checked at 3-5 days after starting when pt has renal a. stenosis or at high risk
In renal impairment secondary to an ACEI, when should termination of the drug be considered?
- hyperkalemia cannot be controlled
- serum creatinine concentration increases more than 30% above baseline value w/i the first 6-8 weeks when BP is reduced
what are the pt risk factors for renal impairment when taking an ACEI
- b/l renal a. stenosis
- hypertensive nephrosclerosis
- HF
- polycystic kidney dz
- chronic kidney dz
what are the techniques to minimize first dose hypotension w/ ACEIs?
- not beginning therapy if the pt is volume depleted
- dc prior diuretic therapy for 3-5 days
- can begin w/ very low dose
mechanism of ACEI induced angioedema
- one of the functions of bradykinins is to increase vascular permeability
- ACEIs block the degradation of bradykinin which leads to a build up of it
- the build up is thought to cause angioedema
treatment of ACEI induced angioedema
- airway management
- dc ACEI - should NEVER be used again
- icatinat: selective breadykinin receptor antagonist - VERY expensive
positive pt. outcomes when using an ARB to treat HFrEF
- they are reasonable to reduce mortality and morbidity as alternatives to ACEIs
- reduced hospitalization and mortality have been demonstrated even though ACEIs are first choice
ARBs MoA
directly blocks the actions of AII, a potent vasoconstrictor and stimulator of the release of aldosterone
contraindications/precautions for ARB use
- pregnancy/breastfeeding
- angioedema
- hyperkalemia
- hypotension
- declining renal fxn
monitoring parameters for ARB use
- assess renal fxn and serum K w/i 1 week and 1 month of initiation of therapy and periodically thereafter
- avoid abrupt withdrawal
- (same as ACEIs)
ADRs for ARBs
- dizziness
- increase in BUN >50%
- cough (lower incidence than ACEIs)
- angioedema
- hypotension
- hyperkalemia >20%
ARNI (angiotensin receptor/neprilysin inhibitor) sacubitril/valsartan (Entresto) MoA
- combines ARB and neprilysin inhibitor
- neprilysin degrades some vasoactive peptides like bradykinin and natriuretic peptides
- natriuretic peptides counter regulate the detrimental effect of the upregulation of RAAS (Na/water retention and vasocontriction)
- inhibition of neprilysin increased peptide levels, decreasing vasoconstriction, Na and water retention
- valsartan is an ARB
contraindications for Entresto
- hx of angioedema
- concomitant use or use w/i 36 hrs of an ACEI
MoA of beta blockers
- cardioselective beta blockers block β1 receptors in the heart
- non selective blocks both β1 receptors in the heart and β2 receptors in the body at all doses
- related to decreased sympathetic outflow from CNS, reduced CO, and reduced renin release by juxtaglomerular cells in the kidney
monitoring parameters for beta blockers
- heart rate
- BP
- rhythm
what are 3 beta-blockers that are associated w/ decreased mortality?
- bisoprolol (Zebeta)
- carvedilol (coreg)
- extended release metoprolol succinate (Toprol XL)
positive patient outcomes for beta blockers
- they reduce the risks of dz progession, clinical deterioration and sudden death
- can reduce the risk of death and combined risk of death or hospitalization
- long term tx can lessen sx of HF, improve clinical status, enhance overall wellbeing
- addition of beta blocker to low dose ACEI produced greater improvement in sx and reduction in risk of death more so than increase in ACEI dose
beta blocker contraindications
- 2nd or 3rd degree AV blocks
- severe bradycardia
- decompensated HF
- sick sinus syndrome
explain the need to prescribe a loop diuretic w/ a beta blocker
-diuretics are needed to maintain Na and fluid balance and prevent exacerbation of fluid retention
monitoring parameters for beta blockers
- HR
- BP
- rhythm
what are the 4 types of ADRs that occur w/ beta blockers?
- fluid retention and worsening HF
- slowing HR and heart block
- hypotensive sx
- fatigue
tx of fluid retention in beta blocker use
- usually not a reason for permanent withdrawal of tx
- pts generally respond well to intensification of conventional therapy and then remain excellent candidates for long term beta blocker tx
tx of bradycardia or heart block with beta blocker use
- generally asymptomatic and requires no tx
- if brady is accompanied by dizziness or 2nd/3rd degree block occurs, decrease beta blocker dose
tx of hypotensive sx with beta blocker use
- minimize risk of hypotension by admining the beta blocker and ACEI at different times of day
- may also resolve after decrease in dose of diuretics in pts who are volume depleted
- if hypotension is accompanied by evidence of hypoperfusion, beta blocker should be decreased or dc
tx of fatigue in beta blocker use
- hardest sx to address
- other causes should be considered
aldosterone receptor antagonist MoA
- competitively inhibits the mineralocorticoid receptor to block aldosterone effects in collecting ducts of nephron
- aldosterone stimulates Na reabsorption and K secretion
contraindications for aldosterone receptor antagonist use
- acute renal insufficiency
- hyperkalemia
positive patient outcomes when using an aldosterone antagonist to treat HFrEF
- recommended to reduce morbidity and mortality following an acute MI in pts who have LVEF of 40% or less who develop sx of HF or have hx of DM
- recommended in pts w/ NYHA class II-IV and have LVEF of 35% or less
monitoring parameters for aldosterone antagonists
- serum K and renal function should be checked:
- 3 days after initiating
- 1 week after
- at least monthly for the first 3 mos
- every 3 mos thereafter
- intesify monitoring of K anytime a new med is added that increases serum K
- beware of salt substitutes (they’re usually KCl)
renal function guidelines for aldosterone antagonists
-creatinine should be:
*2.5 mg/dL or less in men
*2.0 mg/dL or less in women
(or estimated GFR >30)
-K should be:
*less than 5.0
what are the strategies to minimize the risk of hyperkalemia in pts treated w/ aldosterone antagonist?
- risk of hyperkalemia is increased w/ concomitant use of higher doses of ACEIs
- most cases, K supplements are dc or reduced
- close monitoring of serum K is required
- at 3 days, then 1 week, and monthly for first 3 mos
hydralazine/nitrate combo MoA
- dilates arteries and veins
- powerful in reducing load on the heart
monitoring parameters for hydralazine/nitrate combo
- BP
- HR
- ANA titer if drug induced lupus is suspected
what is the correct therapeutic digoxin serum concentration?
0.5-0.9 ng/mL
monitoring parameters for digoxin
- serum creatinine
- serum K, Mg, Ca
- serum dig concentration:
- should be drawn at least 6-8 hrs after last dose
- or w/i 5-7 days after any dosage change
drug interactions of digoxin
- concomitant use of clarithromycin, dronedarone, eryhtromycin, amiodarione, itraconazole, cyclosporine, propafenone, cerapamil or quinidine can increase serum dig concentration and likelihood of toxicity
- dose should be reduced if tx w/ these drugs
- low lean body mass and impaired renal function can also elevate serum dig levels (think elderly)
adverse effects of digoxin
- primarily occur with lg doses, esp in the elderly
- major ADRs include:
- cardiac arrhythmias
- GI
- neuro
- overt dig toxicity
What drug should be avoided in people with heart failure?
- NSAIDs and COX-2 inhibitors
- corticosteroids
- metformin
- thiazolidinediones
- non-DHP CCBs
- TNF alpha antagonists
- serotonin agonists
