Opioid Pharmacology

Question 1

classic opioid receptor types

Answer 1

*Mu
*delta
*kappa

*note - all opioid receptors are G protein-coupled receptors

Question 2

opioids (overview)

Answer 2

pain-relieving drugs that act on opioid receptors, which are found in peripheral nerves, the brain, the spinal cord, and the GI tract

Question 3

“orphan” opioid receptor: ORL1

Answer 3

*opioid receptor-like 1
*structural homology with classic-type receptors, but very different affinity for various ligands

Question 4

endogenous opioid peptides

Answer 4

*endorphins, enkephalins, dynorphins
*painful stimuli leads to release of opioid peptides, leading to reduced perception of pain

Question 5

opioids receptors - MOA

Answer 5

*CLOSE voltage-gated CALCIUM (Ca2+) channels on pre-synaptic nerve terminals, which reduces transmitter release
*OPEN POTASSIUM (K+) channels (OK) to hyperpolarize and inhibit post-synaptic neurons

note - all opioid receptors are G protein-coupled receptors

Question 6

opioids - MOA in descending pathways

Answer 6

*opioids activate descending inhibitory neurons that inhibit pain transmission neurons

Question 7

actions of opioids

Answer 7

*analgesia
*euphoria (for most; dysphoria for some)
*sedation
*respiratory depression
*cough suppression
*miosis (pinprick pupils)
*nausea & vomiting
*constipation
*bradycardia

Question 8

sx of opioid withdrawal

Answer 8

*rhinorrhea
*lacrimation
*yawning
*chills
*gooseflesh (piloerection)
*hyperventilation
*hyperthermia
*mydriasis
*muscular aches
*vomiting, diarrhea
*anxiety, hostility

Question 9

which effect of opioids do individuals usually NOT get tolerant to

Answer 9

constipation (body never becomes tolerance to constipation)

Question 10

absorption of opioid medications

Answer 10

*first pass effect!!
*varies among products and individuals
*affects dosing of oral vs other routes of administration

Question 11

distribution of opioid meds

Answer 11

*highest concentration in highly perfused areas (CNS, lungs, liver, etc)
*highly lipophilic drugs (fentanyl) can accumulate in lipid tissue after high/continuing dosing

Question 12

metabolism/excretion of opioid meds

Answer 12

*most are metabolized in liver to polar compounds that are renally excreted

Question 13

uses of opioids

Answer 13

*analgesia
*acute pulmonary edema
*cough
*diarrhea
*shivering
*anesthesia

Question 14

adverse effects of opioids - acute usage

Answer 14

*respiratory depression
*nausea/vomiting
*pruritus (itching)
*urticaria
*constipation
*urinary retention
*delirium
*sedation
*myoclonus
*seizures

Question 15

adverse effects of opioids - chronic usage

Answer 15

*hyperalgesia
*constipation

Question 16

examples of opioids

Answer 16

*opium/heroin
*codeine
*hydrocodone
*morphine
*hydromorphone (Dilaudid)
*fentanyl
*oxycodone
*methadone
*tramadol

Question 17

opium/heroin

Answer 17

*opioid
*actions similar to morphine
*more addictive

Question 18

codeine & hydrocodone

Answer 18

*opioid
*lower binding affinity to mu-receptor than morphine
*lower efficacy than morphine
*often combined with acetaminophen
*codeine used for COUGH > PAIN in US

Question 19

morphine

Answer 19

*prototypical opioid
*pain relief ~ 4 hours
*primarily given IV and oral
-big first pass effect
-PO:IV = 3:1 (chronic)

Question 20

hydromorphone

Answer 20

*opioid
*aka dilaudid
*shorter acting than morphine
*about 5x more potent than morphine
*primarily given IV and oral
-even bigger first pass effect (5:1)

Question 21

fentanyl

Answer 21

*opioid
*very potent; short acting
*pain relief lasts 0.5 - 1 hour after IV dose
*no oral form, but available: IV, transdermal, buccal, SL, lozenge, nasal spray
*can be tricky to dose in the hospital

Question 22

ADEs of meperidine

Answer 22

*anticholinergic effects can result in tachycardia
*negative inotrope on the heart
*metabolite can accumulate and can cause seizures
*WE DO NOT USE MEPERIDINE

Question 23

oxycodone

Answer 23

*opioid
*very potent oral agent
*duration 4-6 hours
*available in immediate and extended-release products and in combination with acetaminophen

Question 24

methadone - MOA

Answer 24

*mu-receptor agonist
*NMDA receptor ANTAGONIST!!!!
*blocks monoaminergic reuptake transporters

Question 25

methadone - uses

Answer 25

*used for pain and opioid maintenance/withdrawal:
-less euphoria than morphine
-LONG half-life (18-36 hrs)

Question 26

tramadol

Answer 26

*MOA: modest affinity for mu-receptor & inhibits reuptake of NE and serotonin
*available orally and used for moderate pain
*ADEs: seizures, serotonin syndrome

Question 27

mixed opioid agonists

Answer 27

*nalbuphine
*butorphanol

Question 28

buprenorphine - MOA

Answer 28

*mixed opioid partial agonist (at mu receptor) /antagonist (at kappa and delta receptors)
*given alone, produces analgesia to a less degree than traditional opioids
*would ANTAGONIZE a potent agonist (ex morphine) if administered together

Question 29

buprenorphine - uses

Answer 29

used to treat opioid dependency!! (and as analgesic)

Question 30

opioid antagonists - meds

Answer 30

*naloxone
*naltrexone

Question 31

opioid antagonists - MOA

Answer 31

*blocks the opioid receptors (esp the mu receptor)

Question 32

naloxone

Answer 32

*opioid antagonist
*duration: 1-2 hrs
*given by injection or nasal spray
*used for ACUTE REVERSAL OF OPIOIDS

Question 33

naltrexone

Answer 33

*opioid antagonist
*half-life = 10 hrs
*given orally
*used in opioid abuse maintenance programs (also alcohol and tobacco abuse)