Heart Failure Flashcards
(58 cards)
1
Q
Describe the compensatory changes in heart failure?
A
- HR: An increase is first compensatory mechanism seen in HF (extrinsic, mediated via baroreceptor response to decreased CO → resulting in increased SNS activity)
- Afterload (resistance against which heart must pump blood): Increased in HF due to reflex increase in SVR (extrinsic, mediated through increased SNS activity)
- Preload (stretch of myocardial cell prior to contraction): Usually increased in HF due to increased BV (extrinsic, mediated via activation of RAAS) and increased venous tone (extrinsic, via activation of SNS)
- Ventricular hypertrophy (myocardial remodeling): Most important INTRINSIC compensatory mechanism resulting in an increase in muscle mass that helps maintain function initially but chronically contributes to a downward spiral in cardiac function
- Natriuretic Peptides: “Beneficial” hormones secreted in response to increased filling pressures. ANP is released from atrial cells in response to atrial distention and via specific receptors enhances Na+ and water excretion, vasodilation, block of renin release and AngII effects on aldosterone release. BNP is released in HF and a close relationship has been found between serum BNP levels and clinical severity of HF.
2
Q
Acute and Chronic effects of compensatory responses- SNS and RAAS activation
A
- Acute benefits of preservation of blood pressure and blood flow
- Chronic progression of heart failure from increased cardiac workload and metabolic demands, ventricular hypertrophy and dilatation, and myocardial damage / fibrosis
3
Q
What are the specific goals of HF managment
A
- reduction of congestion- fluid optimization w/ diuretics
- modulate neurohormonal activation resulting in long-term stabilization, positive remodeling, and increased survival with RAAS antagonist and BB
- improve flow- may be difficult to accomplish pharmacotherapeutically with vasodillators and requires mechanical devices or transplant
4
Q
What drugs for HF are used to improve symptoms only
A
- digoxin
5
Q
What drugs for HF are used to improve sx AND prolong patient survival?
A
- diuretics
- BB
- ACEI
- ARBs
- aldosterone antagonists
6
Q
What drugs for HF are used to prolong survival?
A
hydralazine (decrease afterload) + nitrates (decrease preload)
7
Q
Describe how drugs are prescribed with new onset HF
A
- new dx–> start ACEI (if cannot tolerate ACEI due to cough start ARBs)
- start diuretic for congestive sx and fluid retention - Add BB and titrate up to max dose tolerated
- add spironlactone if pt remains sx despite other drugs
**Add digoxin at any time if pt is in NSR and symptomatic despite tx w/ diuretic, ACEI (or ARBs) and BB OR if pt is in Afib then use as first line therapy
8
Q
How can diuretics help in HF
A
- reverse Na+ and Fluid retention
2. relieve volume overload : dyspnea-peripheral edema
9
Q
Why are loop diuretics preferred with HF
A
- bc of efficacy to augment w/ a thiazide diuretic
- can be used chronically and acutely
10
Q
___ diuretic is commonly used, but some patients respond better to___ or ___ due to better and more reliable absorption
A
Furosemide
torsemide
bumetanide
11
Q
How do ACEIs help in HF
A
- Produce vasodilation (reduce preload) and ↓ aldosterone activation
- Plus antiremodeling effect
*start at low dose and titrate to goal
12
Q
How can ARBs help in HF
A
- used in pts intolerance to ACEI (ie. cough)
* no apparent benefit from dual therapy with ACEI and ARBs
13
Q
How can Sacubitril as combination with ARB valsartan (Entersto) help with HF
A
- used in HFrEF- role evolving, may be considered in place of ACEI for initial therapy in certain HF pts
14
Q
describe the mechanism of action of Neprilysin inhibitor?
A
Neprilysin is an endopeptidase that degrades various vasoactive peptides (ANP-BNP, bradykinin, adrenomedullin). By increasing levels of these peptides neprilysin decreases vasoconstriction, sodium retention, and deleterious cardiac remodeling.
15
Q
Describe the adverse effects /DDI of Neprilysin inhibitors
A
- hypotenion ad hyperkalemia
- cough (less than ACEI though)
- hyperkalemia w/ concurrent use of potassium-sparing diuretics
- worsening of renal fxn if taken with NSAIDs
16
Q
How do BB help with HF
A
- Antagonizes effect of SNS plus antiremodeling effect
- Relative to ACE inhibitors, may exacerbate heart failure inshort run and benefits are delayed
- BUT long-term improvements in LV function and survival are dose-dependent
17
Q
What BB are used in HF
A
Carvedilol (non-selective, B1 and B2)
Metoprolol (B1 selective)
18
Q
Beta-blockers improve cardiac function in heart failure by:
A
decreasing cardiac remodeling
19
Q
When are aldosterone antagonists used in HF
A
- Added to therapy for LVEF less than 30% optimized on ACEI/ARB and β-blocker therapy
- Blocks aldosterone effect on kidney
- ACEI / ARB aldosterone block is incomplete
- Produces additional Na+ loss plus antiremodeling
20
Q
What do you need to monitor closely when taking an aldosterone antagonsit?
A
Carefully monitor serum K+ (less than 5.0) and renal function (GFR over 30 ml/min)
21
Q
What aldosterone antagonists is most commonly used in HF
A
spironolactone
-eplerenone can be used if endocrine side effects (gynocomastea)
22
Q
Describe the beneficial effect of spironolactone in HF:
A
blocks cardiac hypertrophy
23
Q
When are vasodilators added to HF therapy?
A
Added to therapy for patients with persistent symptoms
- Therapy with an ACEI and a beta-blocker ineffective or patients intolerant to both ACEI-ARBs
- Particularly effective in blacks in NYHA class III-IV
24
Q
How are vasodilators beneficial in HF
A
Produces arterial dilation which:
- decrease in afterload
- reduce cardiac work
- less MR
- venous vasodilation (decrease preload)
25
What vasodilators are used in HF
Hydralazine plus isosorbide dinitrate
26
When is digoxin used in HF
1. Added for systolic dysfunction to control symptoms (fatigue, dyspnea, exercise intolerance) in NYHA (II)-III-IV patients and for HF with atrial fibrillation to control the ventricular rate
27
Survival benefits if serum digoxin level between ___ ng/ml – worsen if ___
0.5-0.8ng/ml
over 1.2 ng/ml
28
Describe the mechanism of digoxin
1. Inhibition of membrane Na+-K+ ATPase enzyme on myocardial cell membrane
2. intracellular Na increases as a result and diminishes the gradient for Ca++ extrusion from the cell via Na+/Ca++ exchanger
3. Thus, intracellular Ca++ remains elevated allowing more to be sequestered in the sarcoplasmic reticulum (SR)
4. The increased Ca++ in SR stores leads to increases in the contractile force when released by “trigger” Ca++ entering through the L-type Ca++ channel.
29
What are the INDIRECT electrophysiologic effects of digoxin
1. parasympathomimetic via stimulation of vagal nerve
- slows HR at SA node
- decrease AV node conduction velocity
2. sensitzation of baroreceptors
- reduce sympathetic outflow
- reverse desensitization that occurs in HF
- effect occurs at lower Cp than positive inotropic effect
30
What are the DIRECT electrophysiological effects of digoxin?
(membrane potential effects)
1. increase abnormal automaticity via resting depolarization (Na+-K+-ATPase can’t maintain Em) and oscillatory depolarizations (intracellular Ca++ overload and Ca++-dependent afterpotentials) that predispose the patient to arrhythmias (PVCs → ventricular tachycardia → ventricular fibrillation).
* This action of digoxin is additive with epinephrine and increases the pro-arrhythmic potential of each drug.
31
What can occur with digoxin + epi?
Ca++ overload--> PVCs--> V tach--> Vfib
32
describe the absorption and distribution of digoxin
Absorption: Fairly well absorbed - bioavailability of tablets is unreliable
Distribution -Widely distributed, taken-up avidly by heart, kidney, liver, and
skeletal muscle
33
Describe the metabolism/excretion of digoxin
1. not extensively metabolized (some by bacteria)
| 2. excreted unchanged by KIDNEYS (dosage must be reduce for pts w/ renal failure)
34
___ is only approved oral inotrope.
Digoxin
35
Digoxin provides ___ relief only and leads to a significant reduction in hospitalizations but has little effect on overall mortality (increased mortality from cardiac arrhythmias) unless special care to keep digoxin plasma levels at low end of therapeutic range [0.5-0.8 ng/ml]
symptomatic
36
Digoxin produces ___ effect (moderate but persistent) BUT beneficial effects on survival are more likely to the ____ that occurs at lower plasma levels. This action decreases the abnormally high compensatory sympathetic outflow, reducing heart rate, venous tone with decreased heart size and oxygen demand
positive inotropic
baroreceptor sensitization
37
baroreceptor sensitization from digoxin decreases:
1. the abnormally high compensatory sympathetic outflow,
2. reducing heart rate,
3. venous tone with decreased heart size and
4. oxygen demand
38
Why does hypokalemia predispose you to toxicity with digoxin?
Increased binding of digoxin to Na+-K+-ATPase (less competition w / K+ for binding) and facilitation of abnormal cardiac automaticity.
*K+ and digoxin compete for the same site so hypo-K+ + digoxin = digoxin toxicity
39
what are some side effects from digoxin toxicity
1. GI: both direct [large oral doses] and CNS effects [stimulation of chemoreceptor trigger zone (CTZ)]: nausea, anorexia, vomiting, diarrhea.
2. CNS: vagal and CTZ stimulation (vomiting), disorientation, hallucinations, visual disturbances (aberrations of color perception, yellow halo).
3. endocrine: Gynecomastia / galactorrhea seen rarely in men; due to peripheral estrogenic action or hypothalamic stimulation
40
How do you treat GI disturbances caused from digoxin toxicity?
Generally sufficient to withhold drug. Most common sign in adults
41
How do you treat cardiac arrhtymias (bradycardia) caused from digoxin toxicity?
Monitor serum K+ and EKG and correct electrolyte imbalance (oral K+ supplements)
42
How do you treat more serious cardiac arrhythmias (won't respond to K+) caused from digoxin toxicity?
PVCs--> PSVT
Administer parenteral K+ and monitor EKG, treat with antiarrhythmic agents (lidocaine [does not enhance AV block], phenytoin, propranolol)
43
How do you treat very serious intoxication (suicidal overdose) caused by digoxin toxicity?
produces heart block
Serum K+ already high, antiarrhythmics may lead to cardiac arrest - best to treat with digoxin antibodies (Digibind®)
44
What are some drugs that cause DDI w/ digoxin
1. Diuretics, Amphotericin B
2. Quinidine-verapamil-nifedipine
3. Epi
4. macrolides (azithromyocin-clarithomycin)
45
How does diuretics, amphotericin B interact w/ digoxin and what is the tx
drug-induced hypokalemia
can predispose to digoxin toxicities
Tx: check K+
46
How does Quinidine-verapamil-nifedipine interact w/ digoxin and what is the tx
Displace digoxin from
tissue sites plus ↓ renal clearance --> ↑ digoxin levels
**displacements may also be seen with NSAIDs, amiodarone
Tx: need to reduce digoxin dose
47
How does epi interact w/ digoxin and what is the tx
Sensitizes heart to digitalis-induced arrhythmias via ↑ intracellular Ca++
tx: use cautiously
48
What is the DDI with macrolides and digoxin and how do you tx it?
May reduce intestinal bacteria that metabolize portion of digoxin dose leading to increased digoxin levels.
tx: Need to reduce digoxin dose.
49
What is the mechanism of action of Milrinone (Primacor)
- Increase myocardial contractility by alteration of Ca++ flux through inhibition of phosphodiesterase (increased cAMP levels → increased Ca++ influx) and not via Na+-K+-ATPase inhibition or beta-adrenergic receptor effect).
- Increase in cAMP levels in vascular tissue results in vasodilation beneficial in heart failure so these are known as “inodilators”.
50
what are toxicities associated with Milrinone (Primacor)
1. Ventricular and supraventricular arrhythmias,
2. nausea / vomiting,
3. thrombocytopenia
51
What are benefits of Milrinone (Primacor)
acute: pharmacotherapeutic bridge to transplant
Long-term: uncertain (have NOT been shown to decrease mortality probably due to increased risks of
arrhythmias and may actually increase mortality).
52
What kind of drug is Milrinone (primacor)
phosphodiesterase inhibitor
53
Describe how phosphodiesterase inhibitors and B1 agonist work
1. binding of B1 agonist (dopamine, dobutamine) activates adenylyl cyclase, which produces cAMP
2. cAMP activates PK which then phosphorylates a Ca channel
3. phosphorylation of a Ca channel increases Ca flow into the cell, causing increased force of contraction of heart muscle
4. Phsophodiesterase inhibitors prevent hydrolysis of cAMP and thus prolong the action of PK===> increase contractility
54
What class of drugs are used to reduce fluid retention in HF
diuretics
55
What class of drugs are used to reduce preload in HF
ACEI
| nitrates
56
What class of drugs are used to reduce afterload in HF
ACEI
hydralazine
minoxidil
57
What class of drugs are used to reduce remodeling and/or arrhythmia in HF
BB
aldosterone antagonists
ACEIs
58
What class of drugs are used to increase contractility in HF
digoxin
