Opiods Flashcards
what are the endogenous opioids
endorphins
enkephalins
dynorphins
how do opioids work
- hyperpolarization of nerves by openign potassium and calcium channels in neurons
- inhibition of ascending pathways in CNS
- excitation of descending adrenergic and seratonerigic pathways
pharmacological effect of opioids*
inhibition of pain and pain perceptions sedation adn anxiolysis depression of respiration cough suppression reduction of intestinal motility pupillary constriction nasuea and vomiting at first
what is the main cause of death from opioid overdose
depression of respiration
clinically useful at end of life COPD
what can opioids be used for
pain
diarrhea
coughing
panic breathign - COPD
how do you give opioids
by the mouth
by the clock
by the ladder
what is the WHO pain ladder
mild pain 0-3: acetaminophen and NSAIDS
moderate pain 4-6: mild opioid codiene
severe pain 7-10: strong opioid morphine
must keep all of the pain controls all the way up the ladder bc work in different ways
oral dosing has first pass metabolism so is less effective than IV so why is it still recommended
longer term effect requiring less frequent doses
avoids highs and thus is less addictive
oral dosing safer
why do you dose by the clock
takes less drug to maintain a person drug free than to bring pain down again
avoids euphoria associated with release of pain so less addictive
avoids development of chronic pain syndromes from pain pathway rewiring
why do you dose by the ladder
assures safest and least potent drug required for any case is used
avoids addictive potential bc strong opioids not used until required
codeine
weakest commonly used opioid with little addiction risk
very low potency
pain, diarrhea, coughing, inhibit breathing
tramadol mechanism of action
activates gamma opioid receptor
weak inhibitor of NE and serotonin
less potential for addiciton, greater pain control
oral morphine
poor availability due to first pass metabolism
onset cna take an hour
lasts 3 hours
IV morphine
twice as potent
can be immediate onset or take 2 hours
oxycodone
similar potency to morphine but oral bioavailability
longer half life
dosed at half morphine dose
forms of oxycodone
slow release - oxycotin
with tylenol - percocet, high overdose risk
hydromorphine
oral onset half an hour IV lasts 3 hours peak effect in an hours more potent than morphine used in surgical settings
fentanyl
very lipophilic and potent
sublingual for acute temporary pain 1-2 hrs
transdermal used for long term severe 72 hrs
sufentanyl
more potent than fentanyl
naltrexone
oral opioid inhibitor
reverses psychotomimetic effects of opiate agonists, reverses hypotension and cardiovascular instability
completely shuts off opioid receptor
what can naltrexone be used to treat
alcohol addiction
naloxone
potent opioid antagonist
blocks opioid binding
dont work orally so put in opioids to prevent OD from injection
used for emergency respiratory depression
short half life
methadone
requires special training
less addictive
more potent than morphine
used where patient developed resistance or toxicity to others
why does methadone have high risk of overdose
half life of 5 days but only effective for 6-12 hours
accumulates
how do you switch from one opioid to another
find the equivalent dose and then use 70% of it
when should you discontinue therapy
intolerable side effects
high doses of opioids with no analgesia
evidence of addiction
patient to comfortable makes no effort to increase function may require cognitive bahavoural program
what is tolerance
reduced potency of analgesic effects of opioids following repeated admin
related to opioid receptor regulation
symptoms of opioid withdrawl
yawning sweating tremor fever increase HR insomnia cramps dilated pupils
how do you avoid dependence
decrease dose by 20-30% a day
what is addiction
psychological dependence
how does NE and serotonin mediate pain
inhibit pain signals from reaching higher levels of the brain
how are tricyclic antidepressants used to treat pain
increase serotonin and NE in synapse
take 1-3 weeks so used for chronic
also good to treat comorbidities of depression
selective serotonin reuptake inhibitors side effects and examples
inhibits s reuptake
suicide, sexual dysfunction, impaired platelet aggregation
paroxetine, fluxoxetine, sertraline
serotonis and NE reuptake inhibitors side effects and example
suicidality
serotonin syndrome
venlafaxine
alpha adrenergic agonists
clonidine and tizantidine
many side effects
what drugs act on descending pathways
all antidepressants
alpha adrenergic agonist
what is peripheral sensitization
spontaneous peripheral nerve activity mediated by sodium channel, drugs work here by blocking sodium channels
what are classes of drugs that dampen the sodium channels on nerves
carbamazepine
tricycle antidepressants
topiramate
lidocaine
carbamazepine
anticonvulsant
limits influx of sodium ions across the cell membrane
topiramate
anticonvulsant
limits sodium ions across the cell membrane and antagonizes glutamate receptors
lidocaine
sodium channel blocker
what are descending inhibitory pathways
NE, serotonin, and endorphines inhibit pain signlas from reaching higher levels of brain , drugs work here by inhibiting reuptake or stimulating the adrenergic system
what is central sensitization
release of excitatory NTs in the dorsal horn of the spinal cord, increased calcium transport causes spontaneous impulses and a pain message to the brain
what are meds that prevents central sensitization and how
decrease calcium channel activity by binding to alpha2-delta subunit of presynaptic neurons
gabapentin and pregablin
what is another way to preven tcentral sensitization
NMDA antagonists for receptors in the spinal cord
ketamin
dextromethorphan
methadone
ketamine
NMDA receptor antagonist
decreases central sensitization and modulation by lowering threshold for nerve transduction
reduces effects of substnace p
what are the excitatory NT
glutamate and substance P
dextromethorphan
low affinity uncompetitive NMDA antagonists
binds opioid receptors
could cause serotonin syndrome
methadone
opioid agonist, blocks NMDA receptors, inhibits NE reuptake
what are advantages of methadone
less need for opioid escalation
not active metabolites
highly lipophilic, high bioavailability
