Medchem-Test 3- Renin Angiotension System

Front 1

What are the two major enzymes in the renin-angiotensin system?

Back 1

The renin-angiotensin system consists of two major enzymes, Renin and Angiotensin
Converting Enzyme (ACE).

Front 2

What is the bioactive peptide in the RAS system?

what is its pharmacologic effect?

Back 2

angiotensin II

Angiotensin II is a potent vasoconstrictor that effects peripheral resistance, renal
function and cardiovascular systems.

Front 3

What is angiotensinogen?

Back 3

Angiotensinogen:
· A globular protein formed in the liver; Contains 452 amino acids (Mol. Wt. 58K-61K)
· Abundant in the plasma; Hydrolyzed by Renin to release Angiotensin I.

Front 4

What is Renin?

Back 4

Renin:
· An aspartyl protease produced by the kidney
· A highly specific enzyme responsible for the hydrolysis of Angiotensinogen to form
Angiotensin I.

Front 5

What is angiotensin I?

Back 5

Angiotensin I:
· A decapeptide formed by the hydrolysis of Angiotensinogen; Negligible biological
activity.
· Acted upon by Angiotensin Converting Enzyme (ACE) to form the bioactive peptide
Angiotensin II.

Front 6

What is angiotensin converting enzyme (ACE?

Back 6

Angiotensin Converting Enzyme (ACE):
· A Zn2+ ion containing enzyme (Mol. Wt. 130K)
· Relatively non-specific peptidyldipeptide hydrolase that requires only a tripeptide sequence
as a substrate, but does not cleave peptides with a penultimate prolyl residue
· Hydrolyzes Angiotensin I to the highly bioactive octapeptide Angiotensin II.
· ACE also hydrolyzes other bioactive peptides such as Bradykinin and Substance P.

Front 7

What is angiotensin II?

Back 7

· A physiologically active octapeptide formed by the action of ACE on Angiotensin I
· Angiotensin II is a highly potent vasoconstrictor and can cause rapid rise in blood pressure
· It also stimulates aldosterone production and secretion, while also causing enhanced
release of catecholamine and increased sympathetic discharge.

Front 8

What is angiotensin III?

Back 8

Angiotensin III:
· A heptapeptide formed by removal of the N-terminal aspartate residue of Angiotensin II by a
glutamyl peptidase catalyzed hydrolysis
· Angiotensin III does not have potent vasoconstricting activity, but it is a strong stimulant for
aldosterone secretion.

Front 9

put these terms in the correct order

renin, angiotensin II, angiotensinogen, angiotensin I, ACE, angiotensin III, Na and fluid retention, blood pressure elevation, aldosterone sectretion

Back 9

Angiotensinogen
renin
angiotensin I
ACE
Angiotensin II
peptidase
angiotension III
aldosterone secretion
Na and fluid retention
blood pressure elevation

Front 10

what are the three actions of ACE?

Back 10

The action of ACE results in,
· Generation of a potent hypertensive agent Angiotensin II
· Release of a hypertensive agent Aldosterone
· Degradation of a potent antihypertensive agent Bradykinin (a vasodilator)

Front 11

what three groups can ACE inhibitors be classified as?

What class is captopril, enalapril, fosinopril?

Back 11

Sulfhydryl (SH) group containing inhibitors (e.g. Captopril)
Dicarboxylate-containing inhibitors (e.g. Enalapril)
Phosphonate-containing inhibitors (e.g. Fosinopril)

Front 12

What does captopril have in its structure that could be attributied to skin rashes and taste disturbances?

Back 12

a SH GROUP

Front 13

Is enalapril a prodrug?

Back 13

YES

· Enalapril is a prodrug; Hydrolyzed by esterases in the liver to
form the highly potent ACE inhibitor drug Enalaprilat;

Front 14

Is benazepril a prodrug?

Back 14

YES

Cleavage of the ester moiety produces the active drug benazeprilat.

Front 15

is Fosinopril a prodrug?

Back 15

YES

Cleavage of the ester moiety by
hepatic esterases generates the active drug Fosino

Front 16

how do large hyprophobic funtionalities in the N-ring affect potency?

Back 16

increases potency

Front 17

are Zn-ion binding groups required for potency?

Back 17

YES

Front 18

why is the N-ring carboxylic acid essential in ACE inhibitors?

Back 18

because it mimics the C-terminal carboxylate of ACE substrates

Front 19

What should be avoided when taking ACE inhibitors?

Back 19

do not take metal oxides found in antacids due to binding

Front 20

when are ACE inhibitors contraindicated?

Back 20

during pregnancy (especially 2nd and 3rd trimesters)

Front 21

How are ACE inhibitors eliminated?

Back 21

Renal elimination is the primary route of elimination for majority of the ACE inhibitors;
therefore, dosage should be reduced in patients with renal impairment.

Front 22

what is stimulation of the AT1 receptor do in comparison to AT2 receptor?

Back 22

Stimulation of the AT1 receptor is thought to mediate the majority of the known negative
effects of angiotensin II, such as vasoconstriction, secretion of aldosterone etc.

In contrast, the AT2 receptor is associated with functions such as vasodilation, muscle
relaxation etc.

Front 23

Are ACE inhibitors and bilateral arterial stenosis contraindicated?

Back 23

YES YES

Front 24

What does the AT2 receptor affect pregnancy?

Back 24

AT2 are present in the fetus and may cause teratogenicity

Front 25

Are ARBs contraindicated in pregnancy?

Back 25

YES