Opioid Pharmacology Flashcards
classic opioid receptor types
*Mu
*delta
*kappa
*note - all opioid receptors are G protein-coupled receptors
opioids (overview)
pain-relieving drugs that act on opioid receptors, which are found in peripheral nerves, the brain, the spinal cord, and the GI tract
“orphan” opioid receptor: ORL1
*opioid receptor-like 1
*structural homology with classic-type receptors, but very different affinity for various ligands
endogenous opioid peptides
*endorphins, enkephalins, dynorphins
*painful stimuli leads to release of opioid peptides, leading to reduced perception of pain
opioids receptors - MOA
*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
opioids - MOA in descending pathways
*opioids activate descending inhibitory neurons that inhibit pain transmission neurons
actions of opioids
*analgesia
*euphoria (for most; dysphoria for some)
*sedation
*respiratory depression
*cough suppression
*miosis (pinprick pupils)
*nausea & vomiting
*constipation
*bradycardia
sx of opioid withdrawal
*rhinorrhea
*lacrimation
*yawning
*chills
*gooseflesh (piloerection)
*hyperventilation
*hyperthermia
*mydriasis
*muscular aches
*vomiting, diarrhea
*anxiety, hostility
which effect of opioids do individuals usually NOT get tolerant to
constipation (body never becomes tolerance to constipation)
absorption of opioid medications
*first pass effect!!
*varies among products and individuals
*affects dosing of oral vs other routes of administration
distribution of opioid meds
*highest concentration in highly perfused areas (CNS, lungs, liver, etc)
*highly lipophilic drugs (fentanyl) can accumulate in lipid tissue after high/continuing dosing
metabolism/excretion of opioid meds
*most are metabolized in liver to polar compounds that are renally excreted
uses of opioids
*analgesia
*acute pulmonary edema
*cough
*diarrhea
*shivering
*anesthesia
adverse effects of opioids - acute usage
*respiratory depression
*nausea/vomiting
*pruritus (itching)
*urticaria
*constipation
*urinary retention
*delirium
*sedation
*myoclonus
*seizures
adverse effects of opioids - chronic usage
*hyperalgesia
*constipation
examples of opioids
*opium/heroin
*codeine
*hydrocodone
*morphine
*hydromorphone (Dilaudid)
*fentanyl
*oxycodone
*methadone
*tramadol
opium/heroin
*opioid
*actions similar to morphine
*more addictive
codeine & hydrocodone
*opioid
*lower binding affinity to mu-receptor than morphine
*lower efficacy than morphine
*often combined with acetaminophen
*codeine used for COUGH > PAIN in US
morphine
*prototypical opioid
*pain relief ~ 4 hours
*primarily given IV and oral
-big first pass effect
-PO:IV = 3:1 (chronic)
hydromorphone
*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)
fentanyl
*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
ADEs of meperidine
*anticholinergic effects can result in tachycardia
*negative inotrope on the heart
*metabolite can accumulate and can cause seizures
*WE DO NOT USE MEPERIDINE
oxycodone
*opioid
*very potent oral agent
*duration 4-6 hours
*available in immediate and extended-release products and in combination with acetaminophen
methadone - MOA
*mu-receptor agonist
*NMDA receptor ANTAGONIST!!!!
*blocks monoaminergic reuptake transporters
methadone - uses
*used for pain and opioid maintenance/withdrawal:
-less euphoria than morphine
-LONG half-life (18-36 hrs)
tramadol
*MOA: modest affinity for mu-receptor & inhibits reuptake of NE and serotonin
*available orally and used for moderate pain
*ADEs: seizures, serotonin syndrome
mixed opioid agonists
*nalbuphine
*butorphanol
buprenorphine - MOA
*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
buprenorphine - uses
used to treat opioid dependency!! (and as analgesic)
opioid antagonists - meds
*naloxone
*naltrexone
opioid antagonists - MOA
*blocks the opioid receptors (esp the mu receptor)
naloxone
*opioid antagonist
*duration: 1-2 hrs
*given by injection or nasal spray
*used for ACUTE REVERSAL OF OPIOIDS
naltrexone
*opioid antagonist
*half-life = 10 hrs
*given orally
*used in opioid abuse maintenance programs (also alcohol and tobacco abuse)
