L15

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

HF with reduced EF

Question 4

Why does HF result in ↑renin?

Answer 4

↓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

Question 5

What is ACE2? Fxn?

Answer 5

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

Question 6

What is the normal fxn of ACE?

Answer 6

AGT1 –> AGT2

Question 7

What are the 3 ACE inhibitors you need to know?

Answer 7

Captopril
Enalapril
Lisinopril

Question 8

What are the 2 receptors AGT2 can bind?

Answer 8

AT1 & AT2

Question 9

3 ways to pharm block the RAAS system

Answer 9

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

Question 10

What are 2 angiotensin receptor blockers you need to know?

Answer 10

Losartan

Valsartan

Question 11

What is the renin inhibitor you need to know?

Answer 11

Aliskiren

Question 12

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

Answer 12

Change TPR:

1. Vasoconstrict
2. ↑Sympathetics

Question 13

What is normal AGT2 fxn to create slow ↑BP?

Answer 13

Change renal fxn

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

Question 14

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

Answer 14

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

Question 15

How is the RAAS system connected to bradykinin and prostaglandins?

Answer 15

ACE enzyme

• AGT1 –> AGT2
• Inactivates bradykinin

Question 16

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

Answer 16

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

Question 17

How do ACE inhibitors change bradykinin levels?

Answer 17

No bradykinin inactivation

Question 18

Captopril

• Fxn
• Excretion
• Dosing
• SEs

Answer 18

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

Question 19

Enalapril

• Fxn
• Excretion

Answer 19

ACE inhibitor w/ longer t1/2 than capto

Renal excretion - watch HF pts

Question 20

Fosinopril

• Fxn
• Excretion

Answer 20

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

Question 21

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

Answer 21

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

Question 22

What is the mechanism of aldosterone?

Answer 22

↑Na retention via ENAC

K wasting

Question 23

What are some of the pathophysologic effects of aldosterone?

Answer 23

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

Question 24

How can you block the effects of aldosterone?

Answer 24

Mineralcorticoid receptor antagonists

• Spironolactone
• Eplerenone

Question 25

What happens to AT1 receptors during CHF? Why?

Answer 25

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

Question 26

Why are angiotensin receptor blockers used for HF?

Answer 26

``` 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 ```

Question 27

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

Answer 27

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

Question 28

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

Answer 28

↓of all!!! Stops at the renin - so everything downstream must also go down! No change to bradykinin/PGs

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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

Answer 33

``` Balances RAAS: ↓Na reabsorption Vasodilation ↓Sympa ↓Renin ```

Question 34

What is compensated HF?

Answer 34

ANP balances RAAS to maintain BV

Question 35

How is ANP measured?

Answer 35

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