Opioid Analgesics Flashcards
define narcotic
“sleep-inducing”
better legal than medical term
define opiate
derived from opium
ie) morphine or codeine
define opioid
compound with pharmacology similar to morphine
ie) synthetic drugs or endogenous opioid ligands
define analgesic
pain-relieving
define endogenous opioids
naturally occurring opioids that mimic the actions of exogenous opiates in the brain and periphery
what three genes are endogenous opioids made from
POMC (pro-opio-melano-cortin gene)
Pro-enkephalin gene
Pro-dynorphin gene
what active opioid product does the POMC gene make
B-endorphin
what active opioid product does the pro-enkephalin gene make
met-enkephalin and leu-enkephalin
what active opioid product does the pro-dynorphin gene make
dynorphin-A (also dynorphin-B, neo-endorphins, and leu-enkephalin)
what endogenous opioid binds Mu opioid receptor
B-endorphin and enkephalins
what endogenous opioid binds Delta opioid receptor
mostly enkephalins and some B-endorphin
what endogenous opioid binds Kappa opioid receptor
dynorphin
where are the endogenous opioids working
at descending inhibitory pathway
have inhibitory effect on C pain fibers
what type of receptors are the opioid receptors? ionotropic? muscarinic/metabotropic?
muscarinic/metabotropic
ALL G-PROTEIN-COUPLED
of the three opioid receptors which is the major one and what are its effects
Mu opioid receptor
analgesia, respiratory depression, euphoria, dependence ie) drug addiction
what is an important non-opioid receptor
DM receptor
mediates antitussive effects (anti-cough)
therapeutic effects of opioids
analgesia
antitussive
antidiarrheal
(also mood enhancement and relief of acute pulmonary edema)
Of the three types of pain which does opioids not work well on
neuropathic pain
what is a problem with the antidiarrheal therapeutic effect of opioids
constipation
general effects of opioid analgesia
inc pain threshold (discriminative)
inc pain tolerance (affective/emotional)
selective for analgesia
what general effects of opioid analgesia is unique compared to local anesthetics
inc pain tolerance (local anesthetics don’t do that, they just do the discriminative inc pain threshold) and selective for analgesia (local anesthetics are not selective, they affect other somatosensory modalities as well)
sites of action for opioid analgesia
opioid receptors at C fibers/ascending pain pathways and descending pain inhibitory pathways and cerebral cortex
major receptor of analgesic action
Mu opioid receptor with contribution from Delta opioid receptor
how does the analgesic action if opioids work at the ascending pathway
1) activate Mu opioid receptors on C fibers which blocks opening of Ca channels so NTs/sub P not released
2) activate Mu opioid receptors on spinothalamic neuron enhancing the opening of K+ channels leading to hyperpolarization
(slide 15)
what type of pain does opioid analgesia work on
best agains slow pain/C fiber pain (dull, burning, aching, constant) less effective against fast pain/A-delta fibers (sharp, intense, stinging intermittent pain)
- *good against nociceptive and inflammatory pain
- **bad against neuropathic pain
what is an example of neuropathic pain
postherpetic neuralgia resulting from shingles
how does the analgesic action if opioids work at the descending pain inhibitory pathway
Mu receptors activated in brain to activate descending pain inhibitory pathway that activates enkephalin containing interneurons that synapse onto the terminal end of C-fibers so Mu receptors on C-fibers activated which blocks the opening of Ca channels so NTs/sub P not released and enkephalins also work on spinothalamic neuron by opening K+ channels causing hyperpolarization
RESULT inhibition of pain ascending pathways
(slide 18)
pathway of the descending pain inhibitory pathway
descending serotonergic neurons from Raphe Nucleus
synapse onto enkephalin containing interneurons
synapse onto terminal end of C-fibers and have inhibitory effect on the release of NTs at this terminal end of C-fibers (C-fiber synapses onto spinothalamic neuron to thalamus)
RESULT is inhibition of ascending pain pathway
opioid use in anesthetic settings include
1) as premedication (act as sedative, anxiolytic, analgesic) prior to general anesthetic
2) intraoperatively as adjunct to general anesthetic or as primary general anesthetic
3) spinal anesthesia for thoracic or abdominal surgery or in labor
T/F antitussive effects are not mediated by opioid receptors
true
what receptor mediates antitussive effects
DM receptor
is the DM receptor stereoselective
no
not selective for l or d form of stereoisomer
is the Mu opioid receptor stereoselective
yes
selective for l form of stereoisomer (so no d form)
examples of opioids/opiates in l isomer so levy form so have antitussive and analgesic effect
natural opioids like B-endorphin and opiates like morphine
example of opioids/opiates in d isomer so dextro form so have antitussive but no analgesic activity
dextromethorphan
why might the dextro d form be a good
has antitussive effect but not analgesic so no respiratory depression, euphoria, nausea, or addiction
result of anti-diarrheal effects mediated by opioid receptors
delayed gastric emptying
inc transit time in GI tract
inc water absorption in GI tract
constipation
is there tolerance for the anti-diarrheal effects of opioids
little to no tolerance
common adverse effects of opioids (mostly Mu/MOR mediated)
constipation (#1 complaint) nausea/vomiting sedation miosis (construction of pupils) pruritus
less common adverse effects of opioids (mostly MOR/Mu mediated)
respiratory depression (cause of death from opioid therapy)
urinary retention
cardiovascular effects are indirect (meperidine)
truncal rigidity
dysphoria
physical dependence and addiction
triad of opioid overdose
pinpoint pupils (miosis)
respiratory depression
dec consciousness
direct effect on heart by Meperidine
antimuscarinic activity leading to tachycardia
can tolerance occur with opioids
yes, can occur with continued use
is tolerance to opioids unsafe
generally does not affect safety
is there cross-tolerance among opioids
yes but it can be incomplete
major opioid cautions and contraindications
substance abuse history
drug interactions with SSRIs and sedative hypnotics/anti-psychotics
what to do if substance abuse history
still require pain relief so do not withhold opioids when patient is experiencing severe pain but look for possible analgesic tolerance and prescribe carefully/limit prescription
Drug interactions of opioids with SSRIs
SSRIs combined with certain opioids like meperidine and propoxyphene can can lead to life threatening serotonin syndrome (tachycardia, hypertension, hypertherm, seizures)
drug interactions of opioids with sedative hypnotics/anti-psychotics
sedative hypnotics/anti-psychotics combined with opioids can lead to increased respiratory depression
other possible opioid cautions and contraindications
head injuries pregnancy impaired pulmonary function impaired renal function impaired hepatic function Addison's or hypothyroidism partial agonists (pentazocine) with full agonists (morphine) can precipitate withdrawal
administration routes of opioids
oral buccal sublingual transdermal nasal suppository parenteral (intramuscular, subcutaneous, IV, intrathecal)
what to use with neuropathic pain
antidepressants and anticonvulsants
so atypical analgesics
therapeutic considerations
acute vs chronic pain type of pain goals for onset and duration opioid naive vs opioid dependent GI motility hepatic or renal impairment ability to tolerate oral delivery
first line high efficacy opioid analgesics/agonists AKA strong agonists AKA full agonists
morphine
methadone
fentanyl
second line high efficacy opioid analgesics/agonists AKA strong agonists AKA full agonists
meperidine
low-medium efficacy oral opioid analgesics/agonists AKA mild to moderate agonists
codeine
oxycodone
hydrocodone
characteristics of low-medium oral opioid analgesics/agonists AKA mild to moderate agonists
only available in oral preparations
some drugs have mild to moderate agonists combined with acetaminophen- FDA recommends not using these drugs due to liver toxicity with chronic acetaminophen, also contraindicated in patients with liver impairment/compromised function (i.e. Vicodin, Percocet, Lortab, Roxicet, etc)
mixed kappa agonist-mu antagonists
pentazocine
mixed partial mu agonist-kappa antagonists
buprenorphine
non-analgesic opioids
dextromethorphan aka dextrorphan
antitussive
antagonists
naloxone
competitive antagonists at all opioid receptors but not at non-opioid receptors like DM
primary use of naloxone
treatment for opioid overdose
because of short duration must monitor overdose patient closely and be prepared to administer multiple doses
examples of neuropathic pain
diabetic neuropathy
postherpetic neuralgia
fibromyalgia
phantom limb pain
drugs to use for neuropathic pain
atypical analgesics because don’t always respond to opioids (antidepressants and anticonvulsants)
what to use for treatment of mild pain
aspirin/NSAIDS
acetaminophen
what to use for treatment of moderate pain
aspirin/NSAIDS
acetaminophen
combine above with low to medium efficacy oral opioids
what to use for treatment of severe pain
high efficacy opioids
alone or with adjuncts
