Opiods Flashcards
σ Receptor
non-opioid receptor dysphoric effects
μ Receptor
Opioid receptor
analgesia, euphoria, physical
dependence, bradycardia, GI, and
respiratory depression
K (kappa) Receptor
mediates spinal analgesia, miosis, sedation, and diuresis
General pharmacokinetics of opioids
well absorbed and rapidly distributed, highly lipophilic
exhibits first pass effect and has glucuronidated metabolites - morphine-6-glucoronide, normeperidine
renally excreted
analgesic effects of opiods depend on the strength of the agonist
strong - morphine, methadone, heroin, meperidine, fentanyl
partial - pentazocine
mixed (agnoist and antagonist) - buprenorphine
weak - codiene, hydrocodone
Cardiovascular and Respiratory effects of opiods
Vasodilation and orthostatic hypotension
Reduction of myocardinal oxygen demand and cardiac work
decrease PVR, preload, afterload and treats pulmonary edema
decrease sensitivity of the medulla to carbon dioxide
incresease intracranial pressure - contra with head innjury
Gastrointestinal effects of opioids
constipation, mu receptors in the GI and a decrease in HCL secretion
constriction of spinchter of oddi and uriniary shpincter
prolonged labor - less seen in meperidine
emesis
encourage patient to take docusate, fiber and fluids,
Opioid effects in the eye
parasympathetic - stimulation f the edinger-westphal nucleus of oculomotor nerve
There’s no tolerance in this effect - considered diagnostic
General opioid effects (not respiratory, cardiac, eye or GI)
histamine release
increased prolactin release
inhibition of LH release
supress immunity
adjunct for anesthesia - sedation and analgesia
adjunct opiods for anesthesia
alfentanil
sulfentanil
remifentanil
opioids and preganacy
fetus/baby born with addiction and withdrawal symptoms - irritability, shrill crying, diarrhea and seizures
treat with diazepam, more severe withdrawal: camphorated tincture of opium or oral methadone
opioid tolerance
happens with all of them
opioids can no longer enduce the endocytosis of the μ-opioid receptor (receptor recycling)
receptor uncoupling - dysfunction of structural interaction between the mu receptor and G proteins
need higher dose to reach same effects
miosis and constipation do not reach tolerance
opioid withdrawal
6 to 12 hrs after last dose and ends within 72 hr
symptoms - Rhinorrhea, sweating, lacrimation,
chills, gooseflesh, yawning, anxiety, aggression, mydriasis
longer half life - longer withdrawal - methadone
mechanism behind opioid addiction
bind in the nucleus accumbens,
release dopamine
morphine
Opioid agonist - acts on all opioid receptors
used for moderate to severe pain, reduces dose needed for anesthetic and produces anxiolytic effect
vasodilation - MI
can cause respiratory depression which is fatal
not for use in head trauma patients
intense sedation and respiratory depression when used with other sedatives, alcohol or barbituates.
codiene
Opioid agonist
Mild-moderate pain; metabolized to morphine
Combined with non-opioids to relieve pain
antitussive - cough suppressant
CYP2D6 metabolism
meperidine
Opioid agonist
Rapid onset-short duration of action
Normeperidine (metabolite) can induce CNS stimulation
interacts with MOIs - hyperrexia c oma
strong antimuscarinic - less effect on smooth muscle
Good for use in pregnancy
serotonin syndrome
SSRIs, TCAs, meperidine, dextromethorphan,
St. John’s Wort, linezolid, “triptans”
Symptoms: rigidity, hyperthermia, myclonus,
delirium, hypertension, tachycardia within 24
hrs
Treatment: Benzodiazepines, cyproheptadine,
ventilation
diphenoxylate
Opioid agonist
Antidiarrheal
when combined with atropine reduces abuse potential
Loperamide - a deriviative that does not cross BBB
fentanyl
Opioid agonist
100x more potent than morphine - given as a transdermal patch or transmucosal
highly lipophilic
short acting?
lozenges exist and are used to induce anesthesia in children
contraindication in pregnancy
levorphanol
Opioid agonist
L-isomer of morphine
used to treat moderate to severe pain
The D-isomer Dextromethorphan; is not addictive and a cough suppressant
methadone
Opioid agonist - better bioavialability and longer duration than morphine
treats heroin addication and moderate to severe pain
antagonist at NMDA receptor
heroin
opioid agonist - shcedule I
injected and snorted
chronic injection leads to collapse of vessels
drug is highly lipophilic and metabolized to morphine
use during pregnancy leads to a newborn addicted to heroin and with withdrawal
uses have an increased incidence of HIV and hepatitis
oxycotin had a heroin like effect when crushed and snorted.
tramadol
μ receptor agonist and reuptake inhibitor of NE and 5HT3
miminal opoid toxicities and used for chronic pain - neuropathic
typically combined with acetometaphen
Tapentadol - same but no effect at serotonin
methylnaltrexone
Treats opioid-induced constipation
Does not cross BBB - the compound is methylated
mixed - agonist and antagonist
pentazocine, Butorphanol, Nalbuphine
more affinity for Kappa receptor - retains analgesic effects with less addiction potential
less physical dependence and respiratory depression
psychomimetic effect - pentazocine (kappa)
precipitates withdrawal - decreases effect of full agonists
Buprenorphine
partial mu agonist and at higher doses is an antagonist
kappa receptor blockage
given sublinguil, transdermal and parenteral
similar toxicities to morphine
treats opioid dependence
precipitates withdrawal - decreases effect of full agonists
Naloxone/Naltrexone
opioid antagonist
Naloxone: IV; fast onset for opioid overdose
(1-3 min). Rapid offset. Repeated
administration until opioid is cleared.
approved for use in addicted newborns
Naltrexone - oral with long duration, used for maintenance therapy. Also reduces alcohol cravings
opioid abuse
heroin is most abused - euphoria followed by sedation
rapid tolerance and dependence
MOA at mu and kappa receptors (agonists)
overdose - IV naloxone and ventilation
symptoms - everything is down - stupor, bradycardia, decreased respiration and miosis
withdrawal - methadone or beprenorphine
symptoms of withdrawal - lacrimation, rhinorrhea, yawning, sweating, gooseflesh, tremors
schedule I opiods
Heroin
also Sch 1 - LSD, PCP
no medical use - high addiction
schedule II opiods
morphine
also, cocaine and amphetamine
medical uses - high addiction
schedule III drugs
barbiturates, anabolic steroids
medical use, moderate addiction potential
