Opioid analgesics Flashcards
definition: opium
exudate from poppy seeds containing 20 biologically active components including morphine and codeine
definition: opiate
drug extracted from exudate of the poppy
definition: opioid
natural or synthetic drug that binds to opioid receptors producing agonist effects
what are the endogenous opioids?
endorphins, enkaphalins, dynorphins
what are the endogenous opioid receptors?
mu 1
where are the mu 1 receptors located? what is their function?
outside spinal cord
central interpretation of pain - supraspinal analgesia
where are the mu 2 receptors located? what is their function?
throughout CNS - brainstem and spinal cord
supraspinal and spinal analgesia respiratory depression constipation physical dependence euphoria
what are the metabolites of morphine?
morphine-6-glucoronide (M6G) and M3G
how is morphine metabolized?
glucoronidation
heroin and codeine are metabolized to what compound?
morphine
what GPCRs are associated with opioid binding?
Gi / Go
what is the mechanism of opioid binding to Gi / Go receptors?
inhibition of adenylyl cyclase - decreased cAMP
loss of intracellular calcium and decreased release of NTs
increase postsynaptic opening of potassium - hyperpolarization
what is the mechanism of analgesia for opioids in the ascending pain pathways?
inhibition of afferent pain transmission
peripheral effects
dorsal horn - presynaptic blocking of pain mediating NTs and postsynaptic activation of secondary afferent neurons via increased potassium
opioids have what effect on NTs in the spinal cord? what is the result?
opioids activate GABA neurons in spinal cord
reduced activation of secondary afferent neurons
what is the mechanism of analgesia for opioids in the DESCENDING pain pathways?
blockage of inhibitory GABAergic interneurons
what are the sites of action for opioids in the descending pain pathways?
periaqueductal gray - midbrain
rostral ventral medulla - brainstem
locus coeruleus - pons
what occurs as a result of increased pCO2 following opioid-induced respiratory depression? what is the clinical significance?
reflexive cerebral dilation
contraindication in head trauma
what is the mechanism for opioid-induced cough suppression?
via brainstem chemoreceptor trigger zone (area postrema)
what are the CV effects of opioids?
hypotension and bradycardia
which drug class should be avoided in combination with opioid use? which opioid specifically should be avoided? why?
MAOI
meperidine
hyperpyrexic reaction including hypertension
what are the opioid antagonists? what is their clinical use?
naloxone, naltrexone
opioid overdose
what are the cough suppressant opioid agents?
codeine, dextromethorphan
what is the role of diphenoxylate?
antidiarrheal
what is the role of loperimide?
antidiarrheal
morphine is an agonist at which receptors?
mu, kappa, delta
hydromorphone is how many times more potent than morphine?
7-10x
which opioid antagonist is the primary overdose agent that can reverse CNS and respiratory depression within 30 seconds?
naloxone (IV)
which opioid antagonist is the primary maintenance drug in the treatment of addiction?
naltrexone
how do opioids affect the reward pathway?
modify action of DA in nucleus accumbens and central/ventral tegmental areas
what is the leading cause of opiate dependence and abuse?
euphoria
what agent is the primary pharmacologic intervention used to treat opioid addiction? what is the strategy?
methadone
tapering effect
