3.A-RAAS Inhibitors

Question 1

What are the major hormone products of the RAAS?

Answer 1

angiotensin II
aldosterone

Question 2

How is angiotensin II derived?

Answer 2

angiotensinogen–>angiotensin I (via renin)
angiotensin I–>angiotensin II (via ACE)

Question 3

What are the major actions of angiotensin II?

Answer 3

rapid pressor response (vasoconstriction)
slow pressor response (kidney specific effects)
vascular and cardiac hypertrophy and remodelling (effects on heart tissue)

Question 4

What are the consequences of low pressure to the kidney?

Answer 4

decreased filtration
decreased excretion of toxic substances
decreased tubular pressure–>collapse–>acute renal failure

Question 5

Which cells release renin?

Answer 5

juxtaglomerular cells

Question 6

What are the 3 pathways which release renin?

Answer 6

intra-renal baroreceptors (low renal pressure)
macula densa (low Na in the loop)
B1 adrenergic receptor pathway (SNS activation)

Question 7

What is the binding site for renin?

Answer 7

angiotensinogen

Question 8

Where would you find ACE?

Answer 8

all over the body on endothelial cell surfaces (angiotensin I to II is automatic in many tissues/organs)

Question 9

What are the effects of angiotensin II on reno-vascular tissue?

Answer 9

vasoconstriction in several tissues
in the kidney it constricts efferent arterioles
-increases glomerular pressure forcing more fluid to be
filtered
-results in rapid increase in GFR

Question 10

How is aldosterone released?

Answer 10

released from adrenal gland following stimulation of the angiotensin-type 1 receptor (AT1) by ANG II

Question 11

Where does aldosterone bind?

Answer 11

aldosterone receptors in cells of the distal tubule/collecting tubule

Question 12

What are the actions of aldosterone?

Answer 12

reabsorption of Na and excretion of K
-increased activity of ENaCs
-increased synthesis of ENaCs

Question 13

What is the main mineralocorticoid hormone of the body?

Answer 13

aldosterone

Question 14

What are ACE inhibitors and where do they act?

Answer 14

inhibit ACE activity (ANG I to ANG II conversion)
occurs on endothelial cells throughout circulation

Question 15

True or false: many ACE inhibitors are prodrugs and are not very potent but have good oral bioavailability

Answer 15

true

Question 16

What do all ACE inhibitors end in?

Answer 16

-pril

Question 17

What are the uses of ACE inhibitors?

Answer 17

high blood pressure
-vasodilation and decreased aldosterone secretion

chronic kidney disease
-decreased renal pressure

heart failure and ischemic heart disease
-decreased adverse effects of ANG II and aldosterone on heart
tissue and blood vessels

Question 18

What are some cautions with ACE inhibitors?

Answer 18

reduced blood pressure
dry cough (bradykinin accumulation)
risk of hyperkalemia (aldosterone inhibition)
decreased renal perfusion in vulnerable patients

Question 19

What do ARBs stand for?

Answer 19

angiotensin receptor blockers

Question 20

Where do ARBs act?

Answer 20

inhibit the AT1 receptor (thus blocking actions of ANG II)

Question 21

True or false: the actions of ARBs differ from ACE inhibitors

Answer 21

cap
they both block ANG II induced vasoconstriction and aldosterone release (except ARBs have much lower cough due to degradation of bradykinin)

Question 22

What do all ARBs end in?

Answer 22

-sartan

Question 23

What are the first line blood pressure agents for people with chronic kidney disease?

Answer 23

ACE inhibitors and ARBs

Question 24

What are some of the effects of declined kidney function due to damage?

Answer 24

decreased GFR
increased serum creatinine
difficulties excreting fluid and toxins
leakage of proteins

Question 25

How do DRI agents work?

Answer 25

bind to the active site of renin to prevent the angiotensinogen to ANG I conversion from happening

Question 26

What is the name of the only DRI available in Canada?

Answer 26

aliskiren

Question 27

What do MRAs stand for?

Answer 27

mineralocorticoid receptor antagonist

Question 28

How do MRAs work?

Answer 28

inhibit the aldosterone receptor

Question 29

What are the names of the MRAs?

Answer 29

spironolactone eplerenone

Question 30

True or false: MRAs are very effective blood pressure agents

Answer 30

cap

Question 31

What are the uses for MRAs?

Answer 31

resistant hypertension due to aldosterone excess heart failure (block -ve effects of aldosterone on heart)

Question 32

What are some cautions with MRAs?

Answer 32

increased potassium hormonal effects (partially stimulates progesterone and androgen receptors)

Question 33

What is RAAS?

Answer 33

renin-angiotensin-aldosterone system system that increases blood pressure RAAS over-activity occurs in many CV conditions

Question 34

What is the major determinant of RAAS activation?

Answer 34

renin

Question 35

Where is aldosterone synthesized?

Answer 35

synthesized and released from the adrenal gland following stimulation of the AT-1 receptor by ANGII

Question 36

How does aldosterone counteract diuretics?

Answer 36

aldosterone promotes the re-absorption of Na while diuretics try inhibit the re-absorption of Na

Question 37

True or false: aldosterone is the only hormone made in the adrenal gland

Answer 37

false the adrenal gland also makes cortisol and dehydroepiandrosterone

Question 38

Aside from ACE, which other enzyme is inhibited by ACE inhibitors?

Answer 38

kininase II

Question 39

What does long-standing hypertension increase risk for (in regards to kidney)?

Answer 39

chronic kidney disease -increased pressure can damage glomerulus, damaging filter function

Question 40

When is ACEI and ARB use considered to be risky?

Answer 40

vulnerable people (poor renal blood flow) -dehydrated -renal artery stenosis

Question 41

What is a major contraindication for ACEI and ARBs?

Answer 41

renal artery stenosis