Proteau's Study Guide

Question 1

Norepinephrine
which adrenergic receptors does it agonize?
R or S config?
Structural features?
short or long acting?
selective or non-selective?

Answer 1

a1, a2, B1
R
Catechol, primary amine group
short-acting
non-selective

Question 2

Epinephrine
which adrenergic receptors does it agonize?
R or S config?
Structural features?
short or long acting?
selective or non-selective?

Answer 2

a1, a2, B1, B2
R
Catechol, secondary amine group
short-acting
non-selective

Question 3

what does COMT do?

Answer 3

transfers a methyl group onto the oxygen -> hydrogen leaves, CH3 is replaced

Question 4

what does MOA do?

Answer 4

replaces NH2 with CO2H

Question 5

1 or B carbon means?

Answer 5

2 carbons away from N group

Question 6

2 or a carbon means?

Answer 6

C adjacent to N group

Question 7

if a drug has a COOH group, what enzyme interacts with it and what is the process it undergoes called?
Adding a COOH group to a drug that acts as norepinephrine makes it what?

Answer 7

L-AAAD causes decarboxylation

prodrug

Question 8

drugs containing ester groups (COO) require what enzyme for activation?

Answer 8

ester hydrolysis

Question 9

what does N-isopropyl look like? how does this effect MAO metabolism?

Answer 9

N connected to a C that has two methyl groups attached

slows down MAO metabolism

Question 10

structure containing N-isopropyl has selectivity for which receptor(s)?
what is the exception?

Answer 10

B1 and B2

only B2 selective if structure cannot undergo COMT

Question 11

what does N-t-butyl look like? how does this effect MAO metabolism?

Answer 11

N connected to a C that has three methyl groups attached

blocks MAO metabolism

Question 12

structure containing N-t-butyl has selectivity for which receptor(s)?

Answer 12

B2

Question 13

if you add a methyl to the 2/a position, what receptor is it selective towards?
will the drug undergo MAO metabolism?

Answer 13

a2

no, blocked by a-methyl group

Question 14

dobutamine has predominantly what receptor agonist activity?

Answer 14

B1

Question 15

For B2s, if no COMT what is primary route of metabolism?

Answer 15

sulfonation

Question 16

for SABA inhalers, which is sulfonated faster, R enantiomer or S enantiomer?

Answer 16

R enantiomer

Question 17

Which of these is NOT a contributor to the long duration of effect of vilanterol/salmeterol? (2 answers)

a. No metabolism by COMT.
b. Metabolism to a reactive intermediate that can alkylate the receptor, resulting in long term effects.
c. It binds tightly to a second non-polar domain on its target receptor, extending the duration of effect.
d. No metabolism by MAO.
e. The high lipophilicity leads to deeper tissue penetration and slowed clearance.
f. Resistance to sulfonation and/or glucuronidation due to the lack of a suitable structural handle for these Phase II reactions.
g. Greater bronchial tissue penetration which leads to decreased clearance from the lungs.

Answer 17

b,f

Question 18

What is NOT true about the drug Mirabegron?

a. No R3 modification
b. Has a “bulky” extended N-group with some polar features
c. No metabolism by COMT
d. No metabolism by MAO
e. Undergoes sulfonation as the primary route of metabolism

Answer 18

e

Question 19

Midodrine is a selective agonist for which receptor?

Answer 19

a1

Question 20

what makes phenylephrine structurally different from epinephrine? it is a selective agonist for which receptor?

Answer 20

has no OH on the 4th carbon in the ring, only has the OH on the 3rd carbon
a1

Question 21

what makes ephedrine structurally different from epinephrine? it is a selective agonist for which receptor?

Answer 21

no OH groups on ring, has a methyl attached to the 2/a Carbon with same stereochemistry as 1/B OH
both a and B

Question 22

what makes pseudoephedrine structurally different from epinephrine?

Answer 22

identical to ephedrine but opposite stereochemistry on the OH group of 1/B Carbon

Question 23

what makes amphetamine structurally different from epinephrine?

Answer 23

Has zero OH groups with an a methyl