63 research outputs found
Buprenorphine maintenance subjects are hyperalgesic and have no antinociceptive response to a very high morphine dose
Objective. Acute pain management in opioiddependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Design. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Setting. Ambulatory. Subjects. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range 5 2–22 mg); no dose change for 1.5–12 months. Ten healthy controls. Methods. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Results. Cold pressor responses (seconds): baseline: control 34 6 6 vs buprenorphine 17 6 2 (P 5 0.009); morphine infusion-end: control 52 6 11(P 5 0.04), buprenorphine 17 6 2 (P> 0.5); electrical stimulation responses (volts): baseline: control 65 6 6 vs buprenorphine 53 6 5 (P 5 0.13); infusion-end: control 74 6 5 (P 5 0.007), buprenorphine 53 6 5 (P> 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P 5 0.03); infusion-end: control 15 (P 5 0.09), buprenorphine 12 (P< 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 6 1, buprenorphine 136 6 10. Conclusions. Buprenorphine subjects, compared with controls, were hyperalgesic (cold pressor test), did not experience antinociception, despite high plasma morphine concentrations, and experienced respiratory depression. Clinical implications are discussed.Peter Athanasos, Walter Ling, Felix Bochner, Jason M. White, and Andrew A. Somogy
Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society
Management of chronic pain with chronic opioid therapy in patients with substance use disorders
Opioid maintained subjects and the effects of high dose morphine and adjuvant analgesics.
Research has shown that maintenance on methadone and buprenorphine for the treatment of opioid addiction can produce the effects of hyperalgesia. This presents difficulties in the management of moderate to severe acute pain in this population. The situation is complicated by a dearth of evidence-based guidelines for pain management. The main aims of the four studies described in this thesis were to examine whether very high intravenous morphine doses alone (55.2 mg)(targeting plasma morphine concentrations of 180 ng/ml), or in combination with ketorolac (185.4 mg)(targeting plasma ketorolac concentrations of 4000 ng/ml), tramadol (229 mg)(targeting plasma tramadol concentrations of 1000 ng/ml) or S(+)-Ketamine (S-ketamine) (14.5 mg)(targeting plasma S-ketamine concentrations of 60 ng/ml) (opioid adjuvants) produced antinociception or respiratory effects in methadone maintained subjects (methadone subjects) and buprenorphine maintained subjects (buprenorphine subjects). The antinociceptive tests of the cold pressor and electrical stimulation were utilised. The effects of different maintenance doses of methadone and buprenorphine were also examined. Methadone maintained subjects were stratified into once daily dose groups of 11-45 (n=6), 46-80 (n=6) and 81-115 (n=6) mg per day. Buprenorphine maintained subjects were stratified into once daily dose groups of 2 to 8 (n=4), 9 to 15 (n=4) and 16-22 (n=4) mg per day. A healthy control group was administered lower doses of morphine alone (11.95 mg), and with adjuvants. The same doses of adjuvants were used in each instance. In the first study high dose morphine failed to provide antinociception for the methadone subjects. High dose morphine significantly decreased respiration rate, but only by an average of 2 breaths per minute. Methadone subjects were hyperalgesic in the cold pressor test. There were no differences in the antinociceptive responses of the different stratified methadone groups to the high dose morphine. Methadone subjects maintained on the highest doses had the highest respiratory depression. In the second study buprenorphine subjects performed similarly to methadone subjects in at least three respects: firstly, high dose morphine had little antinociceptive effect; secondly, this dose significantly decreased respiration rate; and thirdly, buprenorphine and methadone subjects were similarly hyperalgesic in the cold pressor test. There were also no differences in the antinociceptive responses of the different buprenorphine groups to the high dose morphine. In the third study tramadol and ketorolac, when combined with high dose morphine, failed to provide antinociception in either the cold pressor or electrical stimulation tests to methadone subjects. The combination of S-ketamine and high dose morphine provided statistically but not clinically significant improvement in antinociception in the cold pressor test. In the fourth study ketorolac and high dose morphine did not provide antinociception in buprenorphine maintained subjects. While the combinations of S-ketamine or tramadol and high dose morphine provided statistically significant antinociception for buprenorphine maintained subjects in the cold pressor test, it was not clear whether this change represented a clinically significant improvement. High dose morphine alone, or combined with opioid adjuvants at these concentrations is unlikely to provide pain relief in this population. The use of higher concentrations of adjuvants in combination with high dose morphine needs to be further evaluated. Other strategies should also be explored that may provide effective pain relief in patients maintained on opioids for the treatment of opioid dependence.Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 201
Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.
Substance related disorders and dual diagnosis
Wherever nurses work they will come across people who have problems with substance use or abuse, whether the substances are licit or illicit. The same can be said of people who have problems with their mental health; they will be found in all areas in which nurses work. Nurses and other health professionals may also have times in their own lives when they experience difficulty with their own mental health or substance use. Problems with the use of substances and with mental health might occur separately or concurrently. It is important that all nurses understand the nature of these issues in order to offer the best care possible. This chapter explores issues of substance use, substance-related disorders and dual diagnosis (mental health problems coexisting with substance-use disorders). It begins by outlining the use of alcohol and other drugs (AOD) in Australia and New Zealand, and highlights the costs of AOD use (excluding tobacco) to the individual, family and community. The pharmacological dimension of psychoactive drugs is explored, terms are defined and the diagnostic criteria for substance abuse are presented. The skills needed to ask the right questions to obtain the best information and to provide a comprehensive AOD assessment are detailed. Specific interventions such as early interventions, brief interventions and harm reduction are explored. The processes for assessing and working with clients who are intoxicated or withdrawing from substances are described
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