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Flashcards in L15 Deck (35):
1

What is the role of neurohormones in response to heart failure short term?

Adaptive responses to ↓CO
Take the stress off the heart
How:
- Vasoconstriction
- Na & H2O retention

2

What is the role of neurohormones in response to heart failure long term?

The short term response has been dragged out - were beneficial but now MALADAPTIVE

3

What type of HF should you sue RAS inhibitors and BB for?

HF with reduced EF

4

Why does HF result in ↑renin?

↓CO --> ↓circulating blood volume & ↓BP
3 mechanisms to ↑renin:
1. ↓Pre-glomerular BP
2. ↓NaCl at macula densa
3. ↑NE due to HR sympathetic activation

5

What is ACE2? Fxn?

Enzyme (not ACE)
Counter adverse effects of excess AGT2
- Vasodilation
- Anti-proliferative

6

What is the normal fxn of ACE?

AGT1 --> AGT2

7

What are the 3 ACE inhibitors you need to know?

Captopril
Enalapril
Lisinopril

8

What are the 2 receptors AGT2 can bind?

AT1 & AT2

9

3 ways to pharm block the RAAS system

1. ACE inhibitors
2. Angiotensin receptor blockers
3. Renin inhibitors

10

What are 2 angiotensin receptor blockers you need to know?

Losartan
Valsartan

11

What is the renin inhibitor you need to know?

Aliskiren

12

What is normal AGT2 fxn to create a rapid ↑BP?

Change TPR:
1. Vasoconstrict
2. ↑Sympathetics

13

What is normal AGT2 fxn to create slow ↑BP?

Change renal fxn
1. ↑NA reabsorption
2. ↑Aldosterone = acts directly on ENAC

14

What is normal AGT2 fxn leading to vascular and cardiac hypertrophy?

↑Proto-oncogenes
↑GF
↑Extracellular matrix proteins (collagen)
+ Hemodynamics like ↑afterload and ↑wall tension

15

How is the RAAS system connected to bradykinin and prostaglandins?

ACE enzyme
- AGT1 --> AGT2
- Inactivates bradykinin

16

What is the fxn of bradykinin and PGs? What are their adverse effects?

↓BP
Opposes the action of RAAS
Adverse
- Cough
- Angioedema

17

How do ACE inhibitors change bradykinin levels?

No bradykinin inactivation

18

Captopril
- Fxn
- Excretion
- Dosing
- SEs

ACE inhibitor
Renal excretion - impt for HF
Low dose to avoid SE of higher doses:
- Change in taste, rashes, nephropathy, neutropenia

19

Enalapril
- Fxn
- Excretion

ACE inhibitor w/ longer t1/2 than capto
Renal excretion - watch HF pts

20

Fosinopril
- Fxn
- Excretion

ACE inhibitor w/ longer t1/2 than capto
Renal/bile excretion
- Less sensitive to renal fxn = good for cardiac pts

21

What are the plasma values for AGT2, aldosterone and renin for pts on ACE inhibitors

↓AGT2 & aldosterone
↑renin - lose neg FB
Doesn't matter b/c the downstream effects of renin are blocked by these meds

22

What is the mechanism of aldosterone?

↑Na retention via ENAC
K wasting

23

What are some of the pathophysologic effects of aldosterone?

Volume overload w/ ion imbalance
LVH b/c more collagen synthesis --> remodeling
Endothelial dysfxn -> ischemic vessels

24

How can you block the effects of aldosterone?

Mineralcorticoid receptor antagonists
- Spironolactone
- Eplerenone

25

What happens to AT1 receptors during CHF? Why?

Partial ↓ regulated
B/c heart is trying to compensate for damage
These receptors aren't heart friendly:
- Vasoconstrict
- ↑aldosterone release
- ↑sympa
- Hypertrophy

26

Why are angiotensin receptor blockers used for HF?

B/c selectively block AT1 receptors
Allow all AGT2 produced to work at AT2 receptors:
- Vasodilation
- Anti-proliferative
- Differentiation
Can reverse some of the damage done

27

Why does it make sense that renin and ACE inhibitors block action at both AT1 and AT2 receptors?

B/c stop AGT2 production - can't work at either

28

Renin inhibitors causes plasma levels of:
Renin
AGT1
AGT2
Aldosterone
Bradykinin & PGs

↓of all!!!
Stops at the renin - so everything downstream must also go down!

No change to bradykinin/PGs

29

Angiotensin receptor blockers cause plasma levels:
Renin
AGT1
AGT2
Aldosterone
Bradykinin & PGs

↓Aldosterone
But lose feedback onto renin:
↑renin - ↑AGT1 - ↑AGT2

30

ACE inhibitors cause plasma levels:
Renin
AGT1
AGT2
Aldosterone
Bradykinin & PGs

↓AGT2
↓Aldosterone
- ↑Bradykinin & PGs
↑Renin - ↑AGT1 due to loss of neg FB

31

What are 4 shared benefits of ACE, renin inhibitors, and ARBs

1. Anti-HTN
2. Reverse LVH (huge!!!!)
3. ↓vascular hyperplasia
4. Renal fxn unaffected in diabetics

32

What are the shared adverse effects of ACE, renin inhibitors, and ARBs?

Hyperkalemia
↑risk kidney failure if you have renal artery stenosis
- YOU KNOW THIS
Teratogenic

33

What is the normal fxn of atrial and brain natriuretic peptides - ANP & BNP?

Balances RAAS:
↓Na reabsorption
Vasodilation
↓Sympa
↓Renin

34

What is compensated HF?

ANP balances RAAS to maintain BV

35

How is ANP measured?

Short t1/2 so can't measure directly
Measure cleavage product = NT-proBNP
IMPT b/c used as myocardial injury
- ↑ed levels w/ worse HF