Emmitte Pharmacology

Question 1

Which has better CNS penetration, heroin or morphine?

Answer 1

heroin

prodrug, and is more lipophilic

Question 2

3 C3 methyl ethers:

Answer 2

codeine
oxycodone
hydrocodone

all have “co” in name

Question 3

oxymorphone achieves effects how?

Answer 3

mu agonist

Question 4

nalbupine achieves effects how?

Answer 4

kappa agonist

mu antagonist

Question 5

butorphanol achieves effects how?

Answer 5

kappa agonist

mu antagonist

Question 6

buprenorphine achieves effects how?

Answer 6

partial mu agonist

Question 7

what is the pharmacophore of morphine and derivatives?

Answer 7

4-phenylpoiperadine

Question 8

Opioid receptors are highly selective for __ isomers?

levo or dextro

Answer 8

levo

Question 9

What isomers are used as antitussives?

levo or dextro

Answer 9

dextro

Question 10

How many carbons in R1 group of oxymorphone?

Answer 10

1

Question 11

How many carbons in R1 of naloxone and naltrexone?

Answer 11

3-4

Question 12

How many carbons in R1 group of nalbuphine?

Answer 12

5

Question 13

Naloxone and naltrexone achieve effect how?

Answer 13

antagonism of mu receptors

Question 14

nalbuphine achieves effect how?

Answer 14

kappa agonist

mu antagonist

Question 15

What effect does a hydroxyl at C3 have?

Answer 15

slows CNS penetration, increased affinity, decreases antitussive activity

oxymorphone has OH, hhydromorphone does not

Question 16

An OH at which carbon is associated with histamine release?

Answer 16

C6

morphine

Question 17

Is oral bioavailability enhanced or decreased by methyl ether?

Answer 17

enhanced

O-demethylation must occur for analgesic activity

Question 18

Is morphine-6-glucuronide active?

Answer 18

yes

active metabolite that contributes to analgesic activity

Question 19

What must occur to methyl ether for analgesic activity?

Answer 19

O-demethylation

Question 20

CYP450s do not play a significant role in the metabolism of what two opioids?

Answer 20

hydromorphone
oxymorphone

DDIs less of a concern

Question 21

C3 methoxys (codeine, hydrocodone, oxycodone) require O-demethylation by what CYP for high affinity binding to mu receptor?

Answer 21

2D6

rxn is normally sluggish

Question 22

Replacement of the N-methyl group with __ or __ yields mu receptor antagonists

Answer 22

allyl, cyclopropylmethyl

Question 23

What is methylnaltrexone used to treat?

Answer 23

constipation in pts on chronic opioids

Question 24

Which mu antagonist is a quaternary amine used for constipation?

Answer 24

methylnaltrexone

Question 25

Is buprenorphine a mu antagonist?

Answer 25

no partial mu agonist with 25-50 fold the analgesic potency of morphine

Question 26

Despite the cyclopropylmethyl group, __ is not a mu antagonist - instead a partial mu agonist with 25-50 fold the analgesic potency or morphine

Answer 26

buprenorphine

Question 27

2 major side effects of kappa agonists?

Answer 27

sedation | dysphoria

Question 28

Kappa agonists produce __ respiratory depression, constipation, euphoria, and potential for addiction than mu agonsits

Answer 28

less

Question 29

2 flexible (non-morphine) opioids:

Answer 29

meperidine | fentanyl

Question 30

Does fentanyl have a long or short duration of action?

Answer 30

short redistributes rapidly to other tissues; useful for anesthetic adjuvant use

Question 31

Fentanyl contains the __ group, which engenders a very high affinity for mu receptors and increased lipophilicity, which translates into rapid CNS penetration and fast onset

Answer 31

N-phenyethyl

Question 32

which flexible (non-morphine derivative) opioid can cause serotonin syndrome?

Answer 32

meperidine CI with MAOIs

Question 33

What flexible opioid metabolite can cause neurological side effects?

Answer 33

normeperidine

Question 34

Compounds that interact with CYP__ can effect the exposure of fentanyl and its efficacy/side effects

Answer 34

3A4

Question 35

Which enantiomer of methadone has analgesic activity, R or S?

Answer 35

R

Question 36

Two metabolites of methadone are mechanism-based inhibitors of which CYP?

Answer 36

2C19

Question 37

2 monoamine reuptake inhibitor opioids?

Answer 37

tramadol | tapentanol

Question 38

Each tramadol enantiomer as well as the ___ metabolite of the dextrorotatory enantiomer contributes to pharmacological activity

Answer 38

O-demethylated

Question 39

Tramadol carries a risk of __ syndrome in pts taking SSRIs, MAOIs, TCAs

Answer 39

serotonin