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

Mood disorders

Peter Athanasoshttp://trove.nla.gov.au/work/373945

The mechanics of workforce development

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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

The relationship between childhood trauma, adult trauma, mental illness, drug and alcohol use

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Electrocardiogram characteristics of methadone and buprenorphine maintained subjects

Copyright © 2008 Haworth Press, Inc.There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose +/- standard deviation, 69 +/- 29 mg) and buprenorphine (n = 19, mean daily dose 11 +/- 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 +/- 29 mg/day) than methadone subjects without U waves (60 +/- 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 +/- 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 +/- 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.Peter Athanasos; Aaron L. Farquharson; Peggy Compton; Peter Psaltis and Justin Ha