Emmitte Pharmacology Flashcards
Which has better CNS penetration, heroin or morphine?
heroin
prodrug, and is more lipophilic
3 C3 methyl ethers:
codeine
oxycodone
hydrocodone
all have “co” in name
oxymorphone achieves effects how?
mu agonist
nalbupine achieves effects how?
kappa agonist
mu antagonist
butorphanol achieves effects how?
kappa agonist
mu antagonist
buprenorphine achieves effects how?
partial mu agonist
what is the pharmacophore of morphine and derivatives?
4-phenylpoiperadine
Opioid receptors are highly selective for __ isomers?
levo or dextro
levo
What isomers are used as antitussives?
levo or dextro
dextro
How many carbons in R1 group of oxymorphone?
1
How many carbons in R1 of naloxone and naltrexone?
3-4
How many carbons in R1 group of nalbuphine?
5
Naloxone and naltrexone achieve effect how?
antagonism of mu receptors
nalbuphine achieves effect how?
kappa agonist
mu antagonist
What effect does a hydroxyl at C3 have?
slows CNS penetration, increased affinity, decreases antitussive activity
oxymorphone has OH, hhydromorphone does not
An OH at which carbon is associated with histamine release?
C6
morphine
Is oral bioavailability enhanced or decreased by methyl ether?
enhanced
O-demethylation must occur for analgesic activity
Is morphine-6-glucuronide active?
yes
active metabolite that contributes to analgesic activity
What must occur to methyl ether for analgesic activity?
O-demethylation
CYP450s do not play a significant role in the metabolism of what two opioids?
hydromorphone
oxymorphone
DDIs less of a concern
C3 methoxys (codeine, hydrocodone, oxycodone) require O-demethylation by what CYP for high affinity binding to mu receptor?
2D6
rxn is normally sluggish
Replacement of the N-methyl group with __ or __ yields mu receptor antagonists
allyl, cyclopropylmethyl
What is methylnaltrexone used to treat?
constipation in pts on chronic opioids
Which mu antagonist is a quaternary amine used for constipation?
methylnaltrexone
Is buprenorphine a mu antagonist?
no
partial mu agonist with 25-50 fold the analgesic potency of morphine
Despite the cyclopropylmethyl group, __ is not a mu antagonist - instead a partial mu agonist with 25-50 fold the analgesic potency or morphine
buprenorphine
2 major side effects of kappa agonists?
sedation
dysphoria
Kappa agonists produce __ respiratory depression, constipation, euphoria, and potential for addiction than mu agonsits
less
2 flexible (non-morphine) opioids:
meperidine
fentanyl
Does fentanyl have a long or short duration of action?
short
redistributes rapidly to other tissues; useful for anesthetic adjuvant use
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
N-phenyethyl
which flexible (non-morphine derivative) opioid can cause serotonin syndrome?
meperidine
CI with MAOIs
What flexible opioid metabolite can cause neurological side effects?
normeperidine
Compounds that interact with CYP__ can effect the exposure of fentanyl and its efficacy/side effects
3A4
Which enantiomer of methadone has analgesic activity, R or S?
R
Two metabolites of methadone are mechanism-based inhibitors of which CYP?
2C19
2 monoamine reuptake inhibitor opioids?
tramadol
tapentanol
Each tramadol enantiomer as well as the ___ metabolite of the dextrorotatory enantiomer contributes to pharmacological activity
O-demethylated
Tramadol carries a risk of __ syndrome in pts taking SSRIs, MAOIs, TCAs
serotonin
