opioids Flashcards
faster, myelinated, respond to noxious mechanical stimuli, initial pain sensation
A-delta fibers
slower, unmyelinated axons, respond to thermal, mechanical and chemical stimuli, dull aching or burning pain
C-fibers
t/f: 5x more A-delta fibers than C fibers
FALSE
what nociceptor channels can be activated by acid?
TRPV1 and TASK channels
where do non-steroidal and steroidal anti-inflammatories serve to diminish pain?
at the periphery
where do local anesthetics inhibit pain?
inhibit signaling to CNS
where to opioids inhibit pain?
at the periphery and inhibit CNS activity
4 families of endogenous opioids
- pro-opiomelanocortin peptides
- pro-enkephalin peptides
- prodynorphin peptides
- endomorphins
3 opioid G-protein coupled receptors that all activate G-alpha-inhibitory
- mu
- kappa
- delta
what are the natural agonists of the delta receptor?
met-enkephalin and leu-enkephalin
what is the natural agonist of the mu receptor?
Beta-endorphin
what are the agonists of the kappa receptor?
dynorphin A, B and alpha/beta neo-endorphin
which delta receptor agonist is derived from pro-enkephalin peptides?
met- and leu-enkephalin
Beta-endorphin is derived from _________.
pro-opiomelanocortin (POMC)
where is beta-endorphin made?
pituitary and hypothalamus
opioid receptors activate ________ and _________ which leads to activation of _________ channel which will hyperpolarize the cell.
G-alpha-i, G-betaG-gamma, potassium
activation of G-inhibitory will inhibit __________ and decrease_________ which will reduce protein kinase___ which will reduce ________ entry.
adenyl cyclase, cAMP, A, Ca2+
what effect will Ca2+ reduction and hyperpolarization by opioids have on the synapse (pre and post)?
pre-synaptic: Ca2+ and hyperpolarization reduce transmitter release
post-synaptic: hyperpolarization will diminish AP generation
all 3 opioid receptors can produce which effect?
analgesia
the majority of analgesic drugs act primarily at which receptors?
mu
mu receptors are mainly __________ (pre/post synaptic) and mainly found in ____________.
presynaptic
PAG, sup dorsal horn, nucleus accumbens, amygdala, cerebral cortex and GI tract inhibits peristalsis
how do opioids inhibit ascending pain pathway?
- inhibit excitatory neurotransmitter release at spinal cord
- inhibit transmission of impulse at peripheral sensory nerve
how do opioids inhibit descending pain pathway?
opioids inhibit GABA release
- GABA activates Cl- channel which hyperpolarizes
- opioids inhibit the inhibitor to activate pathway that produces CNS mediated pain inhibition
t/f: ALL opioid analgesics produce analgesia, respiratory depression, constipation, GI spasm, and physical dependence
true
morphine is a prototypic _________ of the mu receptor and produces analgesia w/o _____________ along with a combination of __________ and ________ effects.
full agonist, sedation, stimulatory, depressive
the process of _____________ converts morphine into its inactive, toxic form _____________, or its more active analgesic form _______________.
glucuronidation, morphine-3-glucuronide, morphine-6-glucuronide
morphine affects the motivational-affective component of the _________ system since patients report that pain is still present but not unpleasant.
limbic
____________ is the most serious acute adverse effect of all opioids.
respiratory depression
morphine tolerance develops ___________ after starting tx.
5-7 days
morphine is metabolized by ______ in the liver. M-3-G is the __________ product and M-6-G is the _________ products.
UGT2B7
codeine has a substitution at the ____position which makes it more effective orally than morphine.
3
codeine binds poorly to ______ receptor.
mu
what is codeine’s active form?
codeine-6-glucuronide
which form of morphine can cross the BBB?
M-G-6 and morphine
codeine is given at a dosage of _______. side effects are _______ at this dose, and don’t usually see dependence.
30-60mg/day, minimal
t/f: pain with an inflammatory component should not be treated without an anti-inflammatory drug.
true
the controlled release form of hydrocodone is _________ and has potential for abuse since there is more drug/ pill.
oxycotin
mu receptor antagonists to treat opioid toxicity
naloxone (works rapidly), naltrexone, nalmefene (lasts the longest)
mixed agonist-antagonist rationale
formulate drugs that act on kappa or delta receptors that don’t have major adverse affect
opioids primarily used in dentistry via oral admin
codeine, hydrocodone, oxycodone, pentazocine
pentazocine is an antagonist/ partial agonist for the ____ receptor and and agonist for the _____ receptor.
mu, kappa
dihydrocodeine, oxycodone (percocet), hydrocodone (vicodin) are all similar to _________, all methylated at ____ position and can all be taken_________.
morphine, 3, orally
