Lec 10 Heart Failure Pharm Flashcards Preview

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Flashcards in Lec 10 Heart Failure Pharm Deck (31):
1

What is path of RAAS system?

- angiotensin from liver
- converted to angiotensin I by renin from kidney
- converted to angiotensin II by ACE from lungs
- angiotensin II acts of angiotensin receptors AT1-4

2

What is action of RAAS system if hypotension?

- kidneys sense decrease blood flow --> release renin --> get angiotensin II which causes:

--> systemic vasoconstriction --> higher BP
--> increase sympathetic
--> aldosterone release from adrenal --> Na and fluid retention
--> ADH release from posterior pituitary --> fluid retention
--> increase thirst --> increase blood volume

3

What are the downstream effects of angiotensin II?

changes in peripheral resistance by: direct vasoconstriction, increase sympathetic, ADH and aldosterone release

changes in renal function: increase Na reabsorption, increase renal sympathetic tone

structural changes: increase growth factors, increase afterload increase wall tension leading to vascular and cardiac hypertrophy and remodeling

4

What is prorenin?

- secreted from kidney and extrarenal tissue
- can be converted to renin in JG cells of kidney
- binds the same receptor as renin and activates transcription factors associated with fibrosis

5

Where is renin released from?

JG cells in kidney

6

What is action of renin?

- converts angiotensinogen to angiotensin I
- binds pro-renin receptor to activate fibrosis

7

How is renin regulated?

1. Na delivery to macula densa: less NaCl to macula densa = more renin release

2. intrarenal baroreceptor: less renal perfusion pressure = more renin release

3. B-adrenergic receptor: B1 cell on juxtaglomerular cells; activated by hypotension and as part of sympathetic activationa and cause more renin release

8

What is feedback loop on renin?

Angiotensin II inhibits JG cells from releasing renin

9

What is action of aldosterone?

- reabsorption Na/Cl and H2O
- excretion of K

10

What is equation for GFR?

GFR = Kf * Net filtration pressure

Kf = filtration coefficietn

11

What is equation for net filtration pressure?

(Pgc - πgc) - (Pbc - πbs)

P = hydrostatic
π = oncotic; πbc = 0 normally

12

What happens to afferent/efferent arterioles in kidney with angiotensin II? To Pgc/GFR?

both constricted by efferent constricted more --> high Pgc --> high GFR

13

What happens to afferent/efferent arterioles in kidney with renin inhibitor [aliskiren]? To Pgc/GFR? Albumin? Creatinine?

- efferent dilated more than afferent
--> decreasd kidney flow --> decrease Pgc --> decrease GFR
-- less glomerular pressure, less albumin/ creatinine excretion

14

What is mech of action ACE inhibitor? What processes does it inhibit?

- competitively inhibits ACE
inhibits:
- conversion AT1 to AT2 [so less AT II]
- bradykinin inactivation [so more bradykinin]
- Ac-SDKP stem cell regulator [so more of it]

15

What happens to afferent/efferent arterioles in kidney with ACE inhibitor [lisonopril]? To Pgc/GFR? Albumin? Creatinine?

- efferent dilated more than afferent
--> decreasd kidney flow --> decrease Pgc --> decrease GFR
-- less glomerular pressure, less albumin/ creatinine excretion

16

What are the 3 ACE inhibitors we should know?

- captopril
- enalapril
- lisonopril

17

What is a unique side effect of captopril?

changes in taste

18

What are ARBs?

angiotensin II reeptor antagonists

selective for AT1 receptor over AT2

19

With beta blockers what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII

- low renin activity
- low renin concentration
- no change in angiotensinogen/AT I/ATII

20

With renin inhibitors what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII

- low renin activity = direct inhibition from drug
- high renin conc = feedback from ATII
- low ATI/ATII conc
- no change in angiotensinogen

21

With ACE inhibitors what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII

- high renin activity/conc = feedback from low AT II
- low angiotensinogen
- high AT I
- low AT II = directly inhibited by ACEI

22

With ARBs what happens to:
- renin activity
- renin concentration
- angiotensinogen
- AT I
- ATII

- high renin activity/conc = feedback from low AT II activity
- low angiotensinogen
- high AT I
- high AT II conc = but not active since directly blocked by ARB

23

What is action of bradykinin?

acts on B1 receptors: vasoconstriction

acts on B2 receptors: vasodilation, NO + prostaglandin production --> inflammation

24

What is ANP?

atrial natruiertic peptide
- released from atrial myocytes in CHF when atrial stretch with increase volume to cause kidney to get rid of Na/H2O

25

What is BNP?

brain natruiretic peptide
- released from left ventricular myoacrdium in CHF in response to stretch
- can order BNP level test

26

What is action of ANP/BNP?

- released in response to stretch/fluid overload and cause:

- vasodilation --> decrease BP
- decrease renin/aldosterone/ADH --> more vasodilation + decrease blood volume
- increase GFR --> decrease proximal tubule Na reabsorption --> natriuresis + diuresis

27

How do ANP/BNP decrease BP?

- increase cGMP in vascular smooth muscle
- decrease sympathetic tone

---> vasodilation
---> may prevent cardiac remodeling

28

What is the meh of action of endogenous endothelins?

- potent vasoconstrictor peptide ET-1 produced by vascular endothelium
- G coupled receptors
- causes: decrease BP via release PGI2/NO; then prolonged increase BP via constriction vascular smooth muscle; vascular cell proliferation which can pulmonary arterial hypertension

29

What is mech of action by which digoxin increases contractility?

Direct inhibition NA/K ATPase → increase intracellular Na → NCX doesn't work as well → more Ca stays in cell → more Ca goes to SR → more contractility

30

How does digoxin alter AP?

at first it causes brief prolongation of AP then shortens AP particularly at plateau phase

likely due to increase K conductance

31

What is affect of high cAMP in heart vs vasculature?

heart = more Ca --> more CO
vasculature = inhibits myosin light chain kinase --> arterial and venous dilation --> hypotension