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COX-2 enzyme. nociceptive impulses. In that case, the relevant ques-
(C) It produces no GI bleeding. tion is how nociceptive impulses are transmitted via
(D) It is indicated only for the disease, osteoarthritis. the release of pronociceptive neurotransmitters. The
(E) It increases healing of GI ulcers. question then is to determine which intracellular
3. Morphine produces an analgesic effect due to process favors a block of release of neurotransmit-
(A) A block of potassium efflux from a neuron ters. The correct answer is C because calcium is re-
(B) An increase in c AMP accumulation in a quired for neurotransmitter release. Blocking potas-
neuron sium efflux and increasing calcium channel
(C) A decrease in intracellular calcium in a neuron phosphorylation produce functional depolarization
(D) Interaction with a Gs protein in the neuron and neurotransmitter release. Opioids are coupled
(E) An increase in calcium channel phosphoryla- to Gi (inhibitory proteins) that decrease cAMP.
tion in the neuron 4. C. The purpose of this question is to clarify the
4. -Opioid receptor activation is required to observe functional significance of the activation of opioid re-
(A) Respiratory depression ceptor types. Respiratory depression and bradycar-
(B) Bradycardia dia are associated with the 2-opioid receptor.
(C) Miosis Mydriasis is associated with the -receptor, which is
(D) Mydriasis no longer thought of as opioid. Opioids, via respira-
(E) Hypocapnia tory depression, induce hypercapnia, a build-up of
5. Which of the following statements about fentanyl carbon dioxide. The clinically relevant sign of opioid
patches is true? overdose and opioid use is miosis, pinpoint pupils,
(A) They produce no respiratory depression. mediated by -receptor activation.
(B) They produce anesthesia and analgesia. 5. E. Fentanyl patches have the same effect as fen-
(C) They produce no constipation. tanyl, only in a time-release manner. Thus, the pur-
(D) They can be used during pregnancy. pose of the question is delineation of opioid ef-
(E) They cannot be used in nonambulatory patients. fects respiratory depression and constipation. The
respiratory depression is life-threatening when the
ANSWERS patch is used in nonambulatory patients, and it is
1. D. The purpose of this question is to identify first therefore contraindicated for that purpose.
opioids that produce analgesia and then those with Similarly, fentanyl is a teratogenic drug contraindi-
a metabolite that compounds the analgesic effects cated for use during pregnancy. The fentanyl patch
of the drug by being an active analgesic. Naloxone does not induce anesthesia (loss of consciousness)
and nalmefene are not analgesics but opioid antag- but does produce analgesia.
onists. Codeine is metabolized to an active analgesic
metabolite, morphine. Meperidine and SUPPLEMENTAL READING
propoxyphene have nonanalgesic, excitatory, and Darland T et al. Orphanin FQ/nociceptin: A role in
proconvulsant metabolites. pain and analgesia, but so much more.
2. B. The purpose of this question is to clarify the uses Trends Neurosci 1998;21:215 221.
and limitations of use of the COX-2 selective in- Devi LA. Heterodimerization of G-protein-coupled re-
hibitor celecoxib. Celecoxib, by inhibiting COX-2 ceptors: Pharmacology, signaling and trafficking.
reversibly, will block the activity of both injury- Trends Pharmacol Sci 2001;22:532 537.
26 Opioid and Nonopioid Analgesics 329
Julius D and Basbaum AI. Molecular mechanisms of Wallace JL. Selective COX-2 inhibitors: Is the water
nociception. Nature 2001;413:203 210. becoming muddy? Trends Pharmacol Sci. 1999;20:
Marnett LJ and Kalgutkar M. Cyclooxygenase 2 in- 4 6.
hibitors: Discovery, selectivity and the future. Trends Zadina JE et al. Endomorphins: novel endogenous mu-
Pharmacol Sci 1999;20:465 469. opiate receptor agonists in regions of high mu-
Moran TD et al. Cellular neurophysiological actions of receptor density. Ann NY Acad Sci 1999;897:
nociceptin/orphanin FQ. Peptides 2000;21:969 976. 136 144.
Tseng, L. Evidence for -opioid receptor-mediated -
endorphin-induced analgesia. Trends Pharmacol Sci
2001;22:623 630.
Case Study Opioids and Head Trauma
45-year-old woman is found outside her car af- ANSWER: No opioid should be used immediately. The
Ater hitting a tree. The car appears severely use of an opioid at this stage will block the pupillary
damaged. There is no evidence as to how the responses in her eyes due to miosis, which will de-
woman escaped from the car. It is thought that she tract from immediate diagnosis of a concussion. In
was able to open her door and then fell from the addition, opioids will induce hypercapnia due to
car. When she is discovered, she is conscious but respiratory depression, vasodilation, bradycardia,
disoriented and complaining of severe pain of mul- and hypotension and make a patient in shock less
tiple origins. While in route to the emergency de- stable. Such effects will be intensified if the woman
partment, her pain increases in intensity. Which opi- was drinking prior to the accident. In addition, opi-
oid might be used to ease her pain immediately oids increase intracranial pressure via hypercapnia
upon her arrival at the hospital? and vasodilation, possibly increasing any damage to
the brain. In general a patient in severe pain may be
given a general anesthetic agent.
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