ACEi

Question 1

What triggers the RAAS system

Answer 1

1. Hypovolemia (like dehydration)
2. hypotension

Question 2

_________ is a long peptide which remains inert until renin is triggered

Answer 2

Angiotensinogen

Question 3

__________ is a shorter peptide than angiotensinogen

Answer 3

Angiotensin I

Question 4

____________ is a substrate for ACE

Answer 4

Angiotensin I

Question 5

What does ACE stand for

Answer 5

Angiotensin converting enzyme

Question 6

___________ converts angiotensin 1 to angiotensin 2

Answer 6

ACE

Question 7

What happens when Angiotensin 2 is produced?

Answer 7

1. Sodium retention -> water retention
2. Activated aldosterone
3. feeling of thirst
4. increase contractility of the heart
5. Vasoconstriction to increase BP

Question 8

What will happen when the RAAS system is blocked?

Answer 8

1. Sodium and water excretion (diuresis)
2. Vasodilation
3. Less contractility of the heart

Question 9

Do we have a universal peptidase that breaks down any protein?

Answer 9

No

Question 10

T/F: peptidase are specific, every peptide has a peptidase

Answer 10

True

Question 11

Is Zinc deficency dangerous

Answer 11

Yes
zinc is crucial activity of peptidase

Question 12

What does Zinc do?

Answer 12

1. Zn+2 will form a co-ordination bond with oxygen
2. The carbonyl is now electron deficient -> the bond is susceptible to hydrolysis through nucleophilic attack with hydroxyl group

Question 13

The pocket to the left of Zinc (S1) is only to increase binding (not necessary for inhibitors)

Answer 13

True

Question 14

T/F: The presence of an amino acid to the left of the zinc increases potency of binding

Answer 14

True

Question 15

Proline fits into

Answer 15

S2’

Question 16

T/F: ACEi , ARBs, and Renin antagonists are not teratogenic?

Answer 16

False,
ace, arbs, renin antagonists are teratogenic

Question 17

What is the MOA of captopril

Answer 17

ACE inhibitor

Question 18

Captopril is a dipeptide, does this make it potent or not very potent

Answer 18

not very potent

Question 19

Theraputic uses of captopril

Answer 19

HF, HTN
taken on an empty stomach to increase absorption

Question 20

Side effects of ACEi

Answer 20

1. Hyperkalemia, because the work on aldosterone
2. angioedema
3. dry cough
4. itching
5. fetotoxic
6. thiol might cause allergy

Question 21

How many peptides in enalapril?

Answer 21

Tripeptide
1. proline
2. alanine
3.phenylalanine

Question 22

Enalapril is a prodrug?

Answer 22

Yes to increase absorption
esterase removes ethyl and the carboxylic acid interacts with zinc

Question 23

Where does enalapril enter, which pockets?

Answer 23

S1 + S1’
enalapril more potent than captopril

Question 24

How many peptides in lisinopril

Answer 24

3
1. proline
2. phenylalanine
3. lysine

Question 25

Is lisinopril a prodrug?

Answer 25

No

Question 26

What drugs or supplements interact with ACEi drug class?

Answer 26

1. Potassium supplements or any drugs that increase potassium levels 2. lithium as ACEi increase levels of lithium 3. NSAIDS like ibuprofen, indomethacin, naproxen may reduce BP 4. ARBs -> hypotension, hyperkalemia, renal impairment

Question 27

What should we do if dry cough occurs with ACEi?

Answer 27

Switch to ARBs

Question 28

Blocking the pathway near the beginning or end is more potent?

Answer 28

It is more potent to block the pathway from the beginning but will give more SE near the end is less potent but with less side effects

Question 29

What is the MOA of candesartan

Answer 29

Angiotensin-receptor blocker ARB

Question 30

Theraputic uses of Candesartan

Answer 30

HF, HTN, Substitue for ACEi pt with dry cough

Question 31

Is candesartan safe in pregnancy

Answer 31

NO, C/I in pregnancy

Question 32

T/F; Losartan is a tetrazole

Answer 32

True

Question 33

What interactions will you find in losartan

Answer 33

H bond + pi pi stacking

Question 34

What is MOA of aliskiren

Answer 34

peptido-mimic of angiotensin selective renin inhibitor

Question 35

S/E of aliskiren

Answer 35

diarrhea dry cough angioedema hyperkalemia fetotoxic

Question 36

Theraputic uses of aliskiren

Answer 36

HTN, as effective as ARBs

Question 37

T/F: ACEi have diuretic effects

Answer 37

True

Question 38

T/F: any ACEi have 3 pockets, S1, S1', S2' one of them must contain PROLINE to bind to the substrate

Answer 38

True

Question 39

What is the lead compound of ACEi, and how did they discover it

Answer 39

Captopril, they discovered it by snake bites that caused severe hypotension

Question 40

Captopril is a _________ inhibitor of ACE

Answer 40

Competitive inhibitor of ace

Question 41

Are ACEi C/I in heart issue pts

Answer 41

Yes, because they cause hyperkalemia

Question 42

T/F: only 10% of enalapril gets absorbed by active or passive absorption

Answer 42

True

Question 43

The only way for lisinopril to get absorbed is through active absorption

Answer 43

True

Question 44

Peptido mimics are reversible competitive inhibitors yet it takes a long time to be removed

Answer 44

True

Question 45

Aliskerin is a peptidomimic

Answer 45

True (the OH group in the middle)