Narcotic Analgesics Flashcards
What are the 3 opioid receptors and their distribution?
μ = primary and peripheral sensory neurons, periaqueductal grey matter, nucleus raphe magnus, rostral ventral medulla, thalamus, cortex
κ = hypothalamus, nociception areas
δ = olfactory bulb, cerebral cortex, presynaptic on primary afferent neurons, motor integration areas, and nociception areas
[Note that all 3 major receptors are present in high concentrations in the dorsal horn of the SC. Receptors are present both on SC pain transmission neurons and on the primary afferents that relay the pain message to them. Although opioid agonists directly inhibit dorsal horn pain transmission neurons, they also inhibit the release of excitatory transmitters from the primary afferents. Importantly, the μ receptor is associated with TRPV1 and substance-P-expressing nociceptors, whereas δ-receptor expression predominates in the nonpeptidergic population of nociceptors, including many primary afferents with myelinated axons]
Opioids classified as strong agonists
Fentanyl (+sufentanil, alfentanil,remifentanil) Hydromorphone Meperidine Morphine Methadone Oxymorphone Levorphenol
Fentanyl, hydromorphine, meperidine, morphine, methadone, and oxymorphone are considered strong opioid agonists. What is their MOA (receptors) and clinical application?
MOA: strong μ receptor agonists; variable κ and δ agonists
Clinical: severe pain, anesthesia adjuncts, dependence maintenance (methadone)
Which opioids are considered partial agonists (bind same receptors as strong agonists but with lower affinity)?
What are their clinical applications?
Codeine
Hydrocodone
Clinically: mild-to-moderate pain; cough (codeine), analgesic combinations with NSAIDs or acetaminophen
Which opioids are classified as mixed agonist-antagonists?
Buprenorphine
Nalbuphine
Pentazocine
Butorphanol
MOA and clinical application of Buprenorphine
Partial μ agonist and κ antagonist
Moderate to severe pain; dependence maintenance — reduces craving for alcohol
Of the mixed agonist-antagonists, ______ has a long duration of action, while _______ is parenteral only
Buprenorphine; nalbuphine
MOA and clinical application of Nalbuphine
κ agonist and μ antagonist
Clinically: moderate-to-severe pain
What are some opioid antagonists and what is their primary clinical application?
Naloxone
Naltrexone
Nalmefene
Used to reverse opioid overdose [naltrexone can be used for dependence maintenance]
Of the opioid antagonists, ______ has a duration of about 2 hours, while _____ and ____ last >10 hrs
Naloxone; naltrexone and nalmefene
Which opioid is utilized as an antitussive? What is its MOA?
Codeine, dextromethorphan
Full mechanism uncertain; weak μ agonist, inhibits NE and 5-HT transporters
______ is a weak μ agonist and blocks serotonin reuptake. It is used in cases of moderate pain, often as an adjunctive to opioids in chronic pain states. It causes seizures at toxic levels
Tramadol
What effects might the following physiological states have on opioid metabolism: obesity, elderly, infant, renal failure, or hepatic failure
Obesity: increased risk of overdose (central Vd not reflected by actual body weight)
Elderly: increased sensitivity to opioid, prolonged effect of infusion
Infant: prolonged effect
Renal failure: morphine or pethidine toxicity
Hepatic failure: increased sensitivity to opioids (in severe liver failure only)
General MOA of μ receptor agonists (presynaptic and postsynaptic)
All are linked to G-protein (GPCRs)
Presynaptic μ-receptor activation inhibits calcium influx into sensory neurons, which decreases NT release
Postsynaptic μ-receptor activation increases K+ efflux, which decreases postsynaptic response to excitatory neurotransmission
Which opioid is used for pulmonary edema?
Morphine
