Opioids Flashcards
-any drug, natural or synthetic, that acts at opioid receptors
opioids
-derived from opium poppy, contains many opiate compounds including morphine and codeine
opiates
- at least 3 receptor types (mu, kappa, delta)
- all are Gprotein coupled
- close calcium channels, reducing evoked transmitter release (presynaptic)
- open potassium channels, hyperpolarizing membranes (postsynaptic)
morphine
_____ receptors produce analgesic, sedative, and euphoric effects of opiates, as well as most of untoward side effects
mu
_____ receptors appear to contribute to analgesia at spinal levels
delta
____ receptors may also contribute to analgesia, but primarily results in dysphoria
kappa
- opioid receptors in peripheral tissues
- dorsal horn of spinal cord (IPSPs, inhibition of NT release)
- ventral caudal thalamus
afferent pain transmission from periphery to CNS
- periaqueductal grey matter
- rostral ventral medulla
- dorsal horn of the spinal cord
pain modulating descending paths from the CNS
- analgesia
- euphoria/dysphoria
- sedation
- respiratory depression
- cough suppression
- miosis (parasympathetic, cholinergic)
- truncal rigidity
- nausea and vomiting
CNS effects of opioids
- arterial and venous dilation
- constipation
- biliary colic
- decreased RBF
- decreased uterine tone
- endocrine alterations: increase ADH, prolactin, somatotropin, decreased LH
- histamine: flushing, sweating, rashes and itching
peripheral effects of opioids
- acute or chronic pain (analgesic, no apparent max dose, less effective for neuropathy)
- acute pulm edema or MI, decreases sensation of crisis
- cough, antitussive
- diarrhea
- anesthesia, preop meds
uses of opioids
- respiratory depression (primary cause of death)
- dysphoria
- nausea, vomiting
- constipation
- seizures at high doses, delta mediated
opioid toxicity
- clinically apparent in 2 weeks
- develops to euphoria, resp depression, analgesia, sedation, nausea, cough suppression, antidiuresis
- minimal or none to constipation, seizures, miosis
tolerance
dysphoria, rinorrhea, lacrimation, yawning, chills, vomiting, diarrhea, anorexia, insomnia, anxiety, hostility
-no tolerance but craving can persist
opioid withdrawal
equal to 10mg morphine
equianalgesic dose
morphine, methadone, meperidine, hydromorphone, oxymorphone, fentanyl, alfentanil
high efficacy analgesics (severe pain, trauma, post surgical)
- poor oral bioavailability
- duration 4-5 hours
morphine
- longer acting, 6 hours, plasma half life 24 hours
- good oral bioavailability
- used as maintenance in opioid addicts
methadone
- medium acting 2-4 hours
- antimuscarinic, may cause tachycardia
- metabolized to active metabolite
- psychoactive, can cause seizures
meperidine
- short acting, 1hr
- 100X more potent than morphine
- acts at mu receptors
- poor oral bioavailability
- transdermal available
fentanyl
- very short acting, 15-45min
- very potent, parenteral only
- for brief, painful procedures
alfentanil
codeine, hydrocodone, oxycodone, propoxyphene, tramadol
low to medium efficacy analgesics
low efficacy, metabolized into morphine by CYP2D6
codeine
full agonist, moderate/high efficacy
oxycodone
- propoxyphene like metabolites, inhibits NE and 5HT reuptake
- may have efficacy for neuropathic pain
tramadol
- believed to have less addictive potential and risk of respiratory depression
- used for moderate to severe pain
- also used for opioid addiction
partial or mixed agonist-antagonist analgesics
- mu partial agonist
- maintenance of opioid dependance as depot or in combo with naloxone
buprenorphine
buprenorphine, butorphanol, nalbuphine, pentacozine
partial or mixed agonist-antagonist analgesics
-antidiarrheals, poor permeation of BBB
diphenoxylate, loperamide
codeine and dextromethorphan
antitussives
- opioid antagonist used for acute overdose
- 1-2 hr duration
- high affinity for mu receptors
- used in combo with buprenorphine for maintenance of opioid dependance, and in combo with oxycodone for chronic pain
naloxone, for acute opioid overdose
used to prevent relapse in recovering addicts, or buproprion for weight loss
naltrexone
methylnaltrexone or naloxegol, poor BBB penetration
opioid antagonist, used for constipation
many opioids have low bioavailability due to 1st pass metabolism, except which two?
methadone and codeine
______ is more potent than morphine but has poor BBB permeability, glucoronidated
M-6G
______ and ______ are metabolized into morphine
codeine and heroin
- head injuries
- pregnancy
- impaired pulm function
- hepato or renal compromised patients
- endocrine disorders
contraindications of opioids
pure agonists and mixed-agonist/antagonist _______ analgesia, can precipitate withdrawal symptoms
decrease
opioids + other sedative hypnotics ______ sedation and respiratory depression
increase
opioids + antipsychotics _____ sedation and respiratory depression, _____ risk of seizures
increase, increase
opioids + MAOIs ______ risk of hyperpyrexic coma and hypertension
increase
