Dr. Proteau's Musc Ag/Antag Notes

Question 1

which stereochemical formation of ACh has the lowest energy in solution?

Answer 1

Synclinal

Question 2

which stereochemical formation of ACh is most favored with nicotinic receptors?

Answer 2

Antiplanar

Question 3

which stereochemical formation of ACh is most favored with muscarinic receptors?

Answer 3

Anticlinal

Question 4

which stereochemical formation of ACh has the highest energy?

Answer 4

Synplanar

Question 5

The use of Ach is limited to being directly injected into the eye to cause?

Answer 5

myosis in surgery (constriction)

Question 6

what does the addition of the cyclopropyl ring do to ACh?

Answer 6

locks the conformation of the backbone preventing rotation

Question 7

which isomer of ACTM is the active conformation of ACh at muscarinic receptors?
what is the name for the conformation it is locked into?

Answer 7

trans isomer

anticlinal conformation

Question 8

which isomer is more potent at muscarinic receptors, (+) trans or (-) trans

Answer 8

(+) trans

Question 9

Carbachol: drug class

Answer 9

non-select. muscarinic and nicotinic agonist used as a musc. agonist

Question 10

why does Carbachol have a longer duration of effect?

Answer 10

Carbamate in place of ester

Question 11

how do quaternary ammoniums effect oral bioavailability?

Answer 11

decrease oral bioavailability

Question 12

T/F acetyl B-methylcholine chloride is used as a racemate

Answer 12

True

Question 13

T/F acetyl B-methylcholine chloride is selective for musc Rs as an agonist

Answer 13

True

Question 14

Bethanechol chloride is what drug class?

Answer 14

musc agonist

Question 15

T/F Bethanechol chloride is likely susceptible to hydrolysis

Answer 15

false, fairly resistant to hydrolysis

Question 16

why is Bethanechol chloride poorly oral bioavailable?

Answer 16

due to its carbamate structure

Question 17

T/F Bethanechol chloride is used as a racemate

Answer 17

True

Question 18

which enantiomer of Bethanechol chloride is more active?

Answer 18

S enantiomer

Question 19

2S,3R,5S-muscarine chloride has how many isomers?
drug class?
SEs?

Answer 19

8
musc. agonist
hypersalivation, miosis, sweating

Question 20

muscarinic agonists must have a _ atom capable of bearing positive charge

Answer 20

Nitrogen

Question 21

muscarinic agonists must have a _ atom capable of participating in a hydrogen bond

Answer 21

Oxygen

Question 22

there must be a _______ between the oxygen and nitrogen

Answer 22

2-carbon unit

Question 23

pilocarpine:

drug class?

Answer 23

musc. agonist

Question 24

T/F pilocarpine is a synthetically made product

Answer 24

False, plant natural product

Question 25

what is a side effect of Sjogren's syndrome?

Answer 25

dry mouth

Question 26

Cevimeline: drug class? what does it treat?

Answer 26

musc. agonist | dry mouth due to sjogren's syndrome

Question 27

T/F Cevimeline is used as a racemate

Answer 27

True

Question 28

what route of metabolism does Cevimeline undergo? what is formed? is the formation active or inactive?

Answer 28

Cyp3A4 or 2D6 sulfoxide formation inactive

Question 29

for muscarinic antagonists, what bulky group is important for antagonist action?

Answer 29

bulky ester group

Question 30

T/F atropine is given as a racemic mixture

Answer 30

True

Question 31

what primary effect does atropine have?

Answer 31

pupil dilation

Question 32

if an agonist has an ester group, _ carbons will be between the ester group and the nitrogen if an antagonist has an ester group, _ carbons will be between the ester group and the nitrogen

Answer 32

2 | 3

Question 33

what process inactivates atropine?

Answer 33

hydrolysis

Question 34

which enantiomer of Atropine is active?

Answer 34

S enantiomer

Question 35

what drug is the isolate of Atropine that is only the (-)-S-isomer

Answer 35

hyoscyamine

Question 36

T/F scopolamine is given as a racemic mixture

Answer 36

True

Question 37

which enantiomer of scopolamine is active?

Answer 37

S enantiomer

Question 38

what feature of scopolamine differentiates it from atropine that makes it more chemically reactive?

Answer 38

an epoxide group

Question 39

what side effect does scopolamine have (CNS effect)

Answer 39

CNS depression

Question 40

the expected effective duration of tiotropium bromide would be?

Answer 40

long duration due to a very bulky ester

Question 41

tiotropium bromide is metabolized by?

Answer 41

hydrolysis, P450, and glutathione conjugation at epoxide

Question 42

what metabolism would you expect from aclidinium bromide?

Answer 42

fast metabolism by hydrolysis

Question 43

aclidinium bromide is considered long-acting or short-acting?

Answer 43

long acting

Question 44

what metabolism would you expect from umeclidinium bromide?

Answer 44

no ester hydrolysis, Cyp2D6-O-Dealkjylation, and hydroxylation

Question 45

what unique structural feature does oxybutynin have?

Answer 45

a butyne bridge

Question 46

what metabolism would you expect from oxybutynin?

Answer 46

CYP3A4

Question 47

what are the two metabolites of oxybutynin?

Answer 47

N-desethyl metabolite or secondary amine metabolite

Question 48

which metabolite of oxybutynin is active?

Answer 48

secondary amine metabolite

Question 49

solifenacin succinate is used as what enantiomer?

Answer 49

1S,3R enantiomer

Question 50

what metabolism would you expect from solifenacin succinate?

Answer 50

CYP3A4

Question 51

what are the two metabolites of solifenacin succinate? | which is active? inactive?

Answer 51

4R-hydroxy metabolite or N-oxide metabolite | both inactive

Question 52

what's unique about Fesoterodine?

Answer 52

its a prodrug

Question 53

Tolterodine is used a single _-enantiomer

Answer 53

R

Question 54

what metabolism would you expect from Darifenacin? | are metabolites active? inactive?

Answer 54

3A4 or 2D6 | inactive

Question 55

trospium chloride has no major ___ metabolism

Answer 55

P450

Question 56

trospium chloride is likely metabolized by?

Answer 56

ester hydrolysis

Question 57

glycopyrrolate bromide is currently approved to be used as?

Answer 57

a combo drug for COPD

Question 58

tropicamide is used for?

Answer 58

eye exams

Question 59

Benztropine mesylate is considered what drug class?

Answer 59

antiparkinsonian musc. antag.

Question 60

what unique feature of Benztropine mesylate contributes to its use?

Answer 60

it is lipophilic

Question 61

Biperidon hydrochloride is considered what drug class?

Answer 61

antiparkinsonian musc. antag.

Question 62

what shared feature of Benztropine mesylate and Biperidon hydrochloride contribute to their indication?

Answer 62

non-polar