Dose-Response Pharmacology of Intrathecal Morphine in Human Volunteers

Bailey, Peter L.; Rhondeau, Steven; Schafer, Patrick G.; Lu, Jeff Zhiqiang; Timmins, Bryan; Foster, William; Pace, Nathan L.; Stanley, T. H.

doi:10.1097/00000542-199307000-00010

Cited by 220 publications

(134 citation statements)

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“…46 More importantly, the potency and duration of analgesic action of spinal morphine are similar between humans and monkeys. 44,47,48 In addition, the relative ratios of opioid receptor subtypes, MOP, KOP, and DOP, in the monkey central nervous system are similar to those of receptor densities observed in the cortex and thalamus of humans. 35,42,49 Furthermore, several clinically used MOP agonists in terms of their potencies and therapeutic profiles can be manifested and simulated very well in monkey models.…”

Section: ■ Species Differences In Pharmacological Profiles Of Opioid-supporting

confidence: 52%

The Therapeutic Potential of Nociceptin/Orphanin FQ Receptor Agonists as Analgesics without Abuse Liability

Lin

2012

ACS Chem. Neurosci.

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Although mu opioid (MOP) receptor agonists are the most commonly used analgesics for the treatment of moderate to severe pain in the clinic, the side effects of MOP agonists such as abuse liability limit their value as a medication. Research to identify novel analgesics without adverse effects is pivotal to advance the health care of humans. The nociceptin/ orphanin FQ peptide (NOP) receptor, the fourth opioid receptor subtype, mediates distinctive actions in nonhuman primates which suggests the possibility that activity at this receptor may result in strong analgesia in the absence of virtually all of the side effects associated with MOP agonists. The present review highlights the recent progress of pharmacological studies of NOP-related ligands in primates. Selective NOP agonists, either peptidic or nonpeptidic, produce full analgesia in various assays in primates, when delivered systemically or intrathecally. Yet small molecule NOP agonists do not serve as reinforcers, indicating a lack of abuse liability. Given that NOP agonists have low abuse liability and that coactivation of NOP and MOP receptors produces synergistic antinociception, it is worth developing bifunctional NOP/MOP ligands. The outcomes of these studies and recent developments provide new perspectives to establish a translational bridge for understanding the biobehavioral functions of NOP receptors in primates and for facilitating the development of NOP-related ligands as a new generation of analgesics without abuse liability in humans.

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Section: ■ Species Differences In Pharmacological Profiles Of Opioid-supporting

confidence: 52%

The Therapeutic Potential of Nociceptin/Orphanin FQ Receptor Agonists as Analgesics without Abuse Liability

Lin

2012

ACS Chem. Neurosci.

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“…ITM can also produce dose dependent delayed respiratory depression. 13,17 In a large study of 5,969 patients receiving intrathecal opioids, a 3% incidence of delayed respiratory depression was reported, none of which was life-threatening. 18 Nevertheless case reports of respiratory depression with relatively low doses of ITM exist, particularly involving elderly patients.…”

mentioning

confidence: 99%

Low dose intrathecal morphine facilitates early extubation after cardiac surgery: results of a retrospective continuous quality improvement audit

Parlow

Steele

O’Reilly

2005

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : To document one centre's experience with a multimodal analgesic approach, with or without low dose intrathecal morphine (ITM), in facilitating "fast-track" recovery in patients undergoing cardiac surgery.M Me et th ho od ds s: : Records of 131 consecutive patients who underwent first time elective cardiac surgery during a four-month period in 2000 were reviewed. Patients were divided into two groups: those receiving and those not receiving preoperative low dose ITM (< 5 µg·kg -1 ) as part of a multimodal analgesic technique. Demographic and surgical characteristics, postoperative morphine use, time to extubation and requirement for antiemetics were recorded. R Re es su ul lt ts s: : Overall, 75% of patients were extubated within two hours, and 93% within six hours. Fifty-five patients received, and 76 did not receive, ITM (mean ± SD 259 ± 53 µg) along with a multimodal analgesic technique (parasternal infiltration, acetaminophen and indomethacin, and postoperative iv morphine). Anesthetic technique involved modest dose opioids, volatile agent and propofol infusion. The groups were similar with respect to preoperative, intraoperative and anesthetic characteristics.Mean extubation time for fast-track patients receiving vs not receiving ITM was 75 ± 65 vs 117 ± 85 min (P = 0.003). Intravenous morphine use for the first 12 hr after surgery was also reduced in the ITM group (4.6 ± 4.1 vs 10.0 ± 14.8 mg, P = 0.009). There was no difference in rescue antiemetic or antipruritic requirements, failed fast-tracking, or serious adverse events.C Co on nc cl lu us si io on ns s: : Multimodal postoperative analgesia allowed for uneventful early extubation and low opioid requirements. Low dose ITM further facilitated early extubation, and reduced postoperative analgesic requirements. MIT (4,6 ± 4,1 vs 10,0 ± 14,8 mg, P = 0,009

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“…In addition, side-effects should not occur once opioidinduced analgesia has ended. The incidence of nausea and vomiting has also been reported to decrease in a dosedependent manner [5]. Therefore the use of low-dose intrathecal morphine (100 mg in our study) is justi®ed for such procedures because of the duration of postoperative pain and because of the extremely low risk of respiratory side-effects with these doses in otherwise healthy patients [1±5].…”

Section: Discussionmentioning

confidence: 81%

“…With a dose of 300±400 mg, analgesia for 24 h or more is expected [5] cholecystectomy and spinal analgesia ............................................................................................................................................................................................................................................ respiratory depression while, with lower doses (100± 200 mg) [2,4,5], the duration of action is shorter (< 24 h) and similar to the duration of hospital stay after laparoscopic cholecystectomy. This dose is also convenient with regard to side-effects, especially respiratory depression, which is reported to occur only if doses > 200 mg are used [5]. In addition, side-effects should not occur once opioidinduced analgesia has ended.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary retention or delayed urinary output is not dose dependent [5] and cannot be predicted reliably. The use of , 55, pages 118±124 ........................................................................................................................................................................................................................................... spinal opioid analgesia in ambulatory surgery must therefore be carefully evaluated and clear information should be made available to patients.…”

Section: Discussionmentioning

confidence: 99%

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Analgesic effect of low‐dose intrathecal morphine and bupivacaine in laparoscopic cholecystectomy

et al. 2000

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SummaryWe assessed the peri-operative analgesic ef®ciency of low-dose intrathecal morphine combined with a low dose of bupivacaine after elective laparoscopic cholecystectomy since postoperative pain in such procedures, although less than after a conventional open technique, may be signi®cant, particularly during the ®rst 12±24 h. After informed consent, 34 ASA I or II patients were randomly allocated to one of two groups to receive either a lumbar intrathecal injection of morphine (75 or 100 mg) combined with 5 mg of isobaric bupivacaine (spinal group) or a subcutaneous injection of a saline solution (control group). Intra-operatively, opioid requirements, blood pressure response and heart rate changes after insuf¯ation were recorded. Postoperatively, morphine requirements, pain scores and opioid-related side-effects were assessed by a physician blinded to the randomisation. Intra-operative opioid requirements did not differ signi®cantly between groups. Mean (SD) postoperative morphine requirements were signi®cantly lower in the spinal group [13 (10) vs. 23 (10) mg; p 0.04] as were postoperative pain scores (p < 0.001). Sideeffects were of comparable incidence and severity between groups. Low-dose intrathecal morphine combined with low-dose bupivacaine provided effective postoperative analgesia for elective laparoscopic cholecystectomy.

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Dose-Response Pharmacology of Intrathecal Morphine in Human Volunteers

Cited by 220 publications

References 0 publications

The Therapeutic Potential of Nociceptin/Orphanin FQ Receptor Agonists as Analgesics without Abuse Liability

The Therapeutic Potential of Nociceptin/Orphanin FQ Receptor Agonists as Analgesics without Abuse Liability

Low dose intrathecal morphine facilitates early extubation after cardiac surgery: results of a retrospective continuous quality improvement audit

Analgesic effect of low‐dose intrathecal morphine and bupivacaine in laparoscopic cholecystectomy

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