Drug and alcohol dependence
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Drug Alcohol Depend · Jan 2000
Comparative StudyTrends in opiate-related deaths in the United Kingdom and Australia, 1985-1995.
This paper compares data on rates of opiate overdose mortality in the UK and Australia between 1985 and 1995. Data on rates of ICD 9-coded overdose mortality were obtained from the Office of National Statistics in the UK and from the Australian Bureau of Statistics mortality register. ⋯ The proportion of all deaths attributed to opioid overdose was substantially higher in Australia than in the UK, but methadone appeared to contribute to more opioid overdose deaths in the UK (50%) than in Australia (18%). Given deficiencies in the available data, the reasons for these differences between the two countries are uncertain but a plausible hypothesis is that the greater availability and ease of access to methadone maintenance in the UK contributes to both the lower rate of opioid overdose mortality and the greater apparent contribution that methadone makes to opioid overdose deaths in that country.
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Drug Alcohol Depend · Jun 1999
Comparative Study Clinical TrialOral and intravenous methadone use: some clinical and pharmacokinetic aspects.
A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. ⋯ This difference reached an almost statistically significant value (P = 0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.
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Drug Alcohol Depend · May 1999
Inhibitors of cytochrome P450 differentially modify discriminative-stimulus and antinociceptive effects of hydrocodone and hydromorphone in rhesus monkeys.
The present study was conducted to investigate the role of cytochrome P450 in the discriminative-stimulus and antinociceptive effects of hydrocodone (HC) and hydromorphone (HM) in rhesus monkeys. In morphine-deprived monkeys, morphine dose-dependently reversed naltrexone-lever responding, an effect also produced by HC and HM. HC and HM also produced antinociception in a warm-water tail withdrawal procedure. ⋯ In contrast, naltrexone, but not budipine (10.0 mg/kg) or quinidine (10.0 mg/kg), dose-dependently antagonized the antinociceptive effects of HC. Budipine and quinidine decreased the concentration of HM in plasma without significantly affecting the levels of HC, suggesting that these CYP2D6 inhibitors decreased the conversion of HC HM. Thus, some behavioral effects of HC are not modified by a marked inhibition of CYP2D6, suggesting that these effects of HC are not due to its conversion to HM but, rather, that both HC and HM act directly on mu receptors.
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Drug Alcohol Depend · Oct 1998
Randomized Controlled Trial Clinical TrialEfficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine.
Opioid compounds are commonly used analgesics. After opioid administration, troublesome subjective effects, such as dysphoria, dizziness, nausea, and pruritus, have been reported. While some if not all of these are believed to occur due to central nervous system effects of opioids, the anecdotal reports heard from volunteers in our other studies suggest that a peripheral opioid antagonist reduced some of these effects. ⋯ Oral methylnaltrexone 19.2 mg/kg significantly decreased these four ratings. Plasma methylnaltrexone concentrations at two different oral doses were also measured to correlate between pharmacological effects of the compound and its plasma levels. Our results suggested that methylnaltrexone has a potential therapeutic value in decreasing some undesirable subjective effects associated with opioid medications.