Chemistry of Antihypertensives 2

Question 1

What are circumstances that can lead to Renin release

Answer 1

reduced glomerular filtration, B1 receptor activation, humoral signals

Question 2

What happens when in the RAAS system

Answer 2

Angiotensinogen is converted to Angiotensin I by Renin -> Angiotensin I is converted to Angiotensin II by Angiotensin Converting Enzyme

Question 3

Where does Angiotensinogen originate

Answer 3

The liver

Question 4

What are results of angiotensin II circulation

Answer 4

Na+/H20 reabsorption, increased aldosterone release, vasoconstriction, increased ADH,

Question 5

What are drug targets of RAAS

Answer 5

Renin inhibitors, ACE inhibitors, Aldosterone receptor antagonists, Angiotensin II receptor Antagonists

Question 6

What is the rate limiting enzyme of RAAS

Answer 6

Renin

Question 7

What ion is ACE dependent on, how many peptides does it cut and one what side

Answer 7

Zinc, two peptides on the carboxy side

Question 8

T/F: If a proline is the penultimate amino acid then ACE can’t metabolize it

Answer 8

True

Question 9

What are the two ways that ACE inhibitors can lower BP

Answer 9

Reduces the circulation of Angiotensin II and increases the circulation of bradykinin

Question 10

What is bradykinin

Answer 10

Peptide that vasodilates

Question 11

What gives ACE inhibitors on the market strong binding to ACE

Answer 11

Sulfur to chelate zinc or hydrophobic side group to bind hydrobphobic pockets

Question 12

T/F: All natural amino acids are L

Answer 12

True

Question 13

Why does Captopril need to be taken one hour before dinner

Answer 13

It can create disulfide bonds with food making it inactive

Question 14

What group can replace the sulfur in ACE inhibitors to reduce side effects

Answer 14

carboxylic acids

Question 15

Why are all of the dicarboxylated-containing ACE inhibitors, except lisiniopril, prodrugs/ What group is added to make them prodrugs and increase the action

Answer 15

Increase oral bioavailability, esters

Question 16

If there is no sulfur what function group must be added to bind at the S1 site

Answer 16

Phenyl

Question 17

T/F: There must always be at least one carboxylic acid group so that it will bind at the S2’ site

Answer 17

True

Question 18

What is the main route of metabolism and excretion for most ACE inhibitors

Answer 18

Renal excretion

Question 19

In which class of antihypertensive medications is a biphenyl ring meant to mimic a Tyr-4 residue of peptide involved in the RAAS pathway

Answer 19

Angiotensin Receptor Blockers (ARBs)