Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardio Block > Treatment of CHF > Flashcards

Treatment of CHF Flashcards

0
Q

New Paradigm for CHF Treatment

A

Metabolic stress, apoptosis and remodeling stimulated by AT, aldosterone and NE.
Treatment focuses on inhibiting these hormones!
- early treatment with ACEI/ARBs, aldosterone antagonists, BB
- prevents decline in cardiac function (decompensation).
Prognosis improved, shifting emphasis on prevention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

Old Paradigm for CHF Treatment

A

CHF viewed as a hemodynamic disease; treatment provided only symptomatic relief (digoxin, diuretic, bedrest). POOR PROGNOSIS because none of them addressed the underlying disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

NYHA Class 1

A

Symptoms - none
Presentation - low EF (<50%)
Treatment - ACE-I or ARB, BB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

NYHA Class II

A

Symptoms - moderate exertion
Presentation - dyspnea on exertion, edema
Treatment - add diuretic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

NYHA Class III

A

Symptoms - minimal exertion
Presentation - dyspnea, orthopnea, PND, edema
Treatment - add Digoxin and Spironolactone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

NYHA Class IV

A

Symptoms - at rest
Presentation - refractory edema
Treatment - add IV vasodilators, transplantation/assist devices

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Do we still use the NYHA classification?

A

No, use ACC/AHA guidelines which classifies CHF into stages A-D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the ACC/AHA stages

A

Stage A - at risk (preventive measures, ACEI/ARBs)
Stage B - NYHA I (add BB)
Stage C - NYHA II, III (add diuretic/digoxin/spironolactone)
Stage D - NYHA IV (add IV inotropes, transplant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the primary preventative measures in CHF

A 
HTN 
Lipids
Smoking 
Diabetes 
No ETOH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the MOA and Effects of ACE-I

A

Block ATI to ATII conversion in endothelial cells of the lung to:
- Natriuresis (loss of Na+ in urine)
- Decreased TPR
- Decreased Aldosterone, Increased Na+ excretion
Also increase BRADYKININ levels due to inhibition of bradykinin metabolism. Increased prostaglandin production and increased vasorelaxation may be beneficial or may contribute to side effects

Many are prodrugs (not captopril and lisinopril)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Use of ACE-I

A

Decrease mortality post MI (decrease ATII, increase bradykinin)
Preserves renal function in diabetics
ADVANTAGE: little effect on lipids or sexual funciton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Who should not use ACE-I?

A

AA or low-renin hypertensives respond less favorably (thiazide + ACE-I is HIGHLY EFFECTIVE)

FETOTOXICITY - do not give to pregnant women, those expecting to conceive or those breastfeeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Adverse Effects of ACE-I

A

Most Common: Hypotension (1st dose), Na+ depletion
Next Common: Dry irritating cough
Hyperkalemia
Angioedema - allergic skin/mucosa disease (life threatening; incidence in AA 2-4X greater)
RENAL INSUFFICIENCY due to altered glomerular filtration
Proteinuria, rashes, reduction in blood cell counts, fever (10%), BM depression
Hepatotoxicity, pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

MOA of Angiotensin Receptor Antagonists (ARBs)

A

Selectively block ATI receptors, the CV targets of AngII, so have similar effects to ACE-I –> Vasodilation, Natriuresis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Side Effects of ARBs

A 
DO NOT CAUSE COUGH
1st dose hypotension 
Hyperkalemia
Hepatic dysfunction 
Fetotoxicity 
Olmesartan can cause spruelike enteropathy (chronic diarrhea and nausea, rare but serious)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the only renin inhibitor?

A

Aliskiren - directly inhibits protease activity of renin; causes vasodilation, natriuresis just like ACE-I/ARBs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Side effects of Aliskiren

A

1st dose hypotension
Hyperkalemia
Angioedema
Fetotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the DDI with Aliskiren

A

inhibits p-gp, so caution with erythromycin, amiodarone and other p-gp inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Endocrine effects of ACEI and ARBs

A

Prevents and reverses ANGII mitogenic effects:

  • hypertrophy of cardiac mycoytes
  • hypertrophy of vascular smooth muscle
  • cardiac and vascular fibrosis, remodeling
  • atherosclerosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which is better ACEI or ARB?

A

ACEI preferred unless patient can’t tolerate side effects. Combining shows no increased benefit.

However, evidence of “aldosterone escape” from ACEI in CHF (i.e. the reduction in aldosterone synthesis that is achieved with ACE-I therapy is eventually lost in patients).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why were BBs previously contraindicated in CHF?

A

Beta adrenergic receptor activation increase inotrophy!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do BBs attenuate deleterious effects of?

A

Chronic high levels of NE and EPI, which cause:

  • B-AR downregulation
  • arrhythmias (leading cause of death in class II, III CHF)
  • increased myocardial oxygen consumption/ischemia
  • myocyte apoptosis followed by cardiac fibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the hemodynamic effects of BB in CHF?

A

Short-term: reduced CO, BP (PROBLEMATIC!)
Long-term: increased CO, decreased LVEDP

May see initial worsening of symptoms, then improvement (dose up slowly). USE IN EARLY STAGE CHF –> slows disease progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

BB should worsen CHF but…

A
  1. DIVERSE SIGNALING OF B-AR (acute vs. chronic): Beta receptor binding leads to increase cAMP and phosphorylation of contractile elements that make them more sensitive to Ca2+ (increase the force of contraction and how fast we can remove this calcium from SR)
    - Acute signaling: responding to spikes in NE and EPI (high receptor number required)
    - Chronic signaling: responding to lower but sustained levels of NE/EPI (lower receptor numbers required). When receptors are chronically stimulated, clatherin-coated pits take up receptor and internalize it so that it is no longer able to respond to circulating EPI.
  2. SIGNALING MODALITIES OF GPCR
  3. DESENSITIZATION OF B-AR

SOOO…BB reverse desensitization, increase receptor number, restore fast signaling modes (contractility) over slow signaling modes (gene expression)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are contraindications of BBs

A

Heart block
BRadycardia
Decompensated CHF/need for IV inotropes (dobutamine)
Volume overload

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the only 3 BBs approved for CHF?

A

Metoprolol
Carvedilol
Bisoprolol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Nebivolol

A

BB that potentiates NO in vasculature, is approved for HTN but NOT CHF.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What class of drugs is digitalis?

A

cardiac glycoside: inotrope

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the MOA of digoxin ?

A

increased intracellular availability of Ca2+ for contractile apparatus via inhibition of Na/K+ ATPase –> increase intracellular Na+, decreased intracellular K+

29
Q

What is the overall effects of diuretic therapy in CHF?

A

Promote Na+ and water excretion to reverse edema and pulmonary congestion. Reduce preload, CO NOT INCREASED!

Unlike ACE-I, diuretics DO NOT improve survival or prognosis (except for spironolactone/eplerenone which block other effects of aldosterone)

30
Q

What are some drugs used in diuretic therapy?

A

“High Ceiling” diuretics commonly used: Furosemide (“loop”) Bumetanide

Potassium sparing diuretics commonly used in combination with loop diuretics

  • Aldosterone antagonists: spironolactone, eplerenone
  • Independent of Aldo: triamterene, amiloride are not used in CHF
31
Q

What is the toxicity of diuretics?

A

electrolyte distribuances, hypokalemia, hyponatremia, hypochloremic metabolic alkalosis, azotemia, dehydration, hypotension
ototoxicity: tinnitus, hearing loss (loop diuretics)

32
Q

What are the DDIs with Diuretics?

A

NSAIDs reduce efficacy of diuretics, promote fluid retention

33
Q

Do ACE-I and ARBs also have diuretic effects?

A

YES! Reduce sodium retention by preventing aldosterone release
Effect not always sufficient to prevent edema
Dose of diuretic should be reduced (azotemia)

34
Q

Do Spironolatone and Eplerenone have effects beyond just being diuretics?

A

YES!
Aldosterone has direct mitogenic and fiborgenic effects on myocardium (combined with ATII to stimulate fibrosis). Increased aldosterone may lead to worsened LV function.

35
Q

What is the function of arterial vasodilators?

A

INCREASE CO by DECREASING AFTERLOAD –> Improve hemodynamics of advanced stage HF. These should used be in combo with inotropic agents and diuretics.

improve cardiac performance by reducing the resistance to outflow of blood from the LV. This shifts the pressure-volume curve upward and to the left. Preload is reduced to varying degrees depending on agent.

36
Q

Do arterial vasodilators slow progression of CHF?

A

NO! Just keep patients asymptomatic

37
Q

Direct arterial vasodilators use in CHF

A

REDUCE AFTERLOAD

  • reduced resistance to outflow of blood from LV improve ventricular performance, increase CO
  • improved ventricular emptying also reduces LV pressure during diastole (preload) but effect is relatively modest alone
  • need to combine arterial vasodilator with venodilator (nitrate) to reduce both preload and afterload
38
Q

What is the MOA of Hydralazine

A

vasodilator that acts directly on arterial smooth muscle

39
Q

Adverse effects of Hydralazine

A

Stimulates RAS: peripehral edema, circulatory congestion
Toxicity: nausea, anorexia, drug-induced lupus (rare), can exacerbate angina (coronary steal/reflex tachycardia), +FANA (frequent)

40
Q

When is hydralazine used?

A

Use limited to patients unable to tolerate ACE-I (renal insufficiency, angioedema).

41
Q

Describe the PK of Digoxin

A

LOW THERAPEUTIC WINDOW!!!!!!

  • Excreted by kidney (unchanged in urine) - reduce dose in renal disease, elderly
  • Serum half-life is 36 hours.
  • Loading dose needed for rapid onset of action (i.e. antiarrhythmic action)
  • Plasma concentration correlate roughly with therapeutic effect, toxicity
42
Q

Toxicity of Digoxin

A

Atrial, ventricular arrhythmias, visual changes (blurring, yellow-green halo), headache, fatigue, drowsiness, confusion, seizures

Most frequent visits to emergency room because it has such a narrow therapeutic window!

43
Q

What can be used to neutralize serum digoxin if toxicity occurs

A

Digibind - Ab to digoxin

44
Q

When are nitrates used?

A

used to reduce preload either alone or with vasodilator

  • reduces pulmonary artery pressure, pulmonary congestion
  • reduces LV filling pressure and walls tress
45
Q

What are IV vasodilators

A

Nitrates including Nitroglycerin, Nitroprusside

veno- and vasodilation reduces preload (decreases congestion) and reduces afterload

46
Q

How do you manage advanced CHF?

A

IV vasodilators
IV inotropic agents
Nesiritide
Cardiac transplantation/Extracorporeal Bridging devices

47
Q

What are the Inotropic agents used in advanced CHF?

A

B Agonists: Dobutamine

PDE Inhibitors: Milrinone

48
Q

Describe the PK of Dobutamine

A

B1>B2, also alpha1AR agonist, positive inotrope, vasodilator
Short-term IV “bridge” or intermittent therapy
Limited by Beta AR dessensitization, arrhythmias
BB therapy prevents vasodilator effect of dobutamine and can even cause vasoconstriction (unopposed alpha1 agonist effect)

49
Q

Describe the PK of Milrinone

A

short-term IV use (long term oral use of PDE inhibitors in CHF increases mortality)

50
Q

MOA of Dobutamine

A

B1 selective agonist that activates B1 receptor in cardiac mycotes –> stimulates cAMP production –> activating through PKA –> phosphorylates several important inotropic pathways which cause greater contraction –> increased HR.

51
Q

MOA of Milrinone

A

PDE inhibitor - inhibits enzyme that breaks down cAMP that is stimulated by beta adrenergic receptor activation.

52
Q

What are the two natriuretic peptides and what do they promote in CHF?

A

Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP)
PROMOTE VASODILATION

53
Q

When are natriuretic peptides released?

A

Released from atria and ventricles in response to volume/pressure expansion.
Naturally elevated in CHF
Promotes vasodilation, venodilation and natriuresis

54
Q

What are the hemodynamic effects of natriuretic peptides?

A

reduce ventricular filling pressure (preload)
inhibits renin and aldosterone release
inhibits sodium reabsoprtion in PCT
selective afferent arteriolar vasodilation

55
Q

What is the only BNP for CHF?

A

Nesiritide - recombinant human BNP; FDA approved for IV treatmetn of decompensated class IV CHF

56
Q

Nesiritide MOA

A
  • binds to BNP receptor in vascular smooth muscle, veno- and vasodilation (via cGMP). reduced preload/afterload
  • dilation of afferent renal glomerular arterioles increases GFR, filtration fraction, and decreases sodium reabsoprtion (natriuresis)
  • suppresses renin-angiotensin and SNS
57
Q

Is there a benefit of Nesiritide?

A

Benefit comparable to IV nitroglycerin but hyptoension may persist longer; use should be limited to those who do not respond to nitroglycerin

58
Q

OVERVIEW Digoxin

A

Increase inotropy
Natriuretic
Survival benefit

59
Q

OVERVIEW Milrinone

A

Decrease afterload
Increase inotropy
Natriuretic
NEGATIVE SURVIVAL BENEFIT

60
Q

OVERVIEW Furosemide

A

Decrease preload

Natriuretic

61
Q

OVERVIEW Hydralazine

A

Decreases afterload

Survival benefit

62
Q

OVERVIEW Nitrate

A

Decrease preload

63
Q

OVERVIEW ACE-I and ARBs

A

decrease preload and afterload
anti-mitogenic
natriuretic
survival benefit

64
Q

OVERVIEW Spironolactone

A

decrease preload
anti-mitogenic
natriuretic
survival benefit

65
Q

OVERVIEW Dobutamine

A

Increase/Decrease afterload
Increase inotropy
Natriuretic

66
Q

OVERIVEW Nesiritide

A

decrease preload and afterload
anti-mitogenic
natriuretic

67
Q

OVERVIEW BB

A

Increase/Decrease inotropy
anti-mitogenic
natriuretic
survival benefit

68
Q

What is the primary goal of pharmacology in patients with early stage (Stage A and B) CHF?

A

Reign in the over-activation of neurohumoral mediators such as catecholamines and ATII

69
Q

BB are effective in treating class I-IV CHF because they…

A

block catecholamine-induced overdrive in the heart and restore B-AR function

Cardio Block (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions