ACEi Flashcards
What triggers the RAAS system
- Hypovolemia (like dehydration)
- hypotension
_________ is a long peptide which remains inert until renin is triggered
Angiotensinogen
__________ is a shorter peptide than angiotensinogen
Angiotensin I
____________ is a substrate for ACE
Angiotensin I
What does ACE stand for
Angiotensin converting enzyme
___________ converts angiotensin 1 to angiotensin 2
ACE
What happens when Angiotensin 2 is produced?
- Sodium retention -> water retention
- Activated aldosterone
- feeling of thirst
- increase contractility of the heart
- Vasoconstriction to increase BP
What will happen when the RAAS system is blocked?
- Sodium and water excretion (diuresis)
- Vasodilation
- Less contractility of the heart
Do we have a universal peptidase that breaks down any protein?
No
T/F: peptidase are specific, every peptide has a peptidase
True
Is Zinc deficency dangerous
Yes
zinc is crucial activity of peptidase
What does Zinc do?
- Zn+2 will form a co-ordination bond with oxygen
- The carbonyl is now electron deficient -> the bond is susceptible to hydrolysis through nucleophilic attack with hydroxyl group
The pocket to the left of Zinc (S1) is only to increase binding (not necessary for inhibitors)
True
T/F: The presence of an amino acid to the left of the zinc increases potency of binding
True
Proline fits into
S2’
T/F: ACEi , ARBs, and Renin antagonists are not teratogenic?
False,
ace, arbs, renin antagonists are teratogenic
What is the MOA of captopril
ACE inhibitor
Captopril is a dipeptide, does this make it potent or not very potent
not very potent
Theraputic uses of captopril
HF, HTN
taken on an empty stomach to increase absorption
Side effects of ACEi
- Hyperkalemia, because the work on aldosterone
- angioedema
- dry cough
- itching
- fetotoxic
- thiol might cause allergy
How many peptides in enalapril?
Tripeptide
1. proline
2. alanine
3.phenylalanine
Enalapril is a prodrug?
Yes to increase absorption
esterase removes ethyl and the carboxylic acid interacts with zinc
Where does enalapril enter, which pockets?
S1 + S1’
enalapril more potent than captopril
How many peptides in lisinopril
3
1. proline
2. phenylalanine
3. lysine
Is lisinopril a prodrug?
No
What drugs or supplements interact with ACEi drug class?
- Potassium supplements or any drugs that increase potassium levels
- lithium as ACEi increase levels of lithium
- NSAIDS like ibuprofen, indomethacin, naproxen may reduce BP
- ARBs -> hypotension, hyperkalemia, renal impairment
What should we do if dry cough occurs with ACEi?
Switch to ARBs
Blocking the pathway near the beginning or end is more potent?
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
What is the MOA of candesartan
Angiotensin-receptor blocker ARB
Theraputic uses of Candesartan
HF, HTN, Substitue for ACEi pt with dry cough
Is candesartan safe in pregnancy
NO, C/I in pregnancy
T/F; Losartan is a tetrazole
True
What interactions will you find in losartan
H bond + pi pi stacking
What is MOA of aliskiren
peptido-mimic of angiotensin
selective renin inhibitor
S/E of aliskiren
diarrhea
dry cough
angioedema
hyperkalemia
fetotoxic
Theraputic uses of aliskiren
HTN, as effective as ARBs
T/F: ACEi have diuretic effects
True
T/F: any ACEi have 3 pockets, S1, S1’, S2’ one of them must contain PROLINE to bind to the substrate
True
What is the lead compound of ACEi, and how did they discover it
Captopril, they discovered it by snake bites that caused severe hypotension
Captopril is a _________ inhibitor of ACE
Competitive inhibitor of ace
Are ACEi C/I in heart issue pts
Yes, because they cause hyperkalemia
T/F: only 10% of enalapril gets absorbed by active or passive absorption
True
The only way for lisinopril to get absorbed is through active absorption
True
Peptido mimics are reversible competitive inhibitors yet it takes a long time to be removed
True
Aliskerin is a peptidomimic
True (the OH group in the middle)
