Articles: narcotic-antagonists.
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Training and distributing naloxone to drug users is a promising method for reducing deaths associated with heroin overdose. Emergency Medical Service (EMS) providers have experience responding to overdose, administering naloxone, and performing clinical management of the patient. Little is known about the attitudes of EMS providers toward training drug users to use naloxone. ⋯ Providers with greater number of years working in EMS were more likely to view naloxone trainings as effective in reducing overdose death. Provider concerns included drug users' inability to properly administer the drug, program condoning and promoting drug use, and unsafe disposal of used needles. Incorporating information about substance abuse and harm reduction approaches in continuing education classes may improve the attitudes of provider toward naloxone training programs.
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Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin over-dose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. ⋯ Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.
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Randomized Controlled Trial Clinical Trial
Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex.
Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4 times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004 mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was significantly greater than that of placebo (P < .001), oxycodone qid (P = .006), and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality of analgesia (P = .002), duration of pain control each day (P = .05), patients' global assessments (P = .04), and the Western Ontario and MacMaster Universities Osteoarthritis Index total score (P = .03). The incidence of side effects was comparable between active treatments. In this Phase II dose-ranging study, Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid. ⋯ Preclinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence. Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence.
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To examine the relationship between key patient variables and variation in naloxone dose (from the standard dose of 1.6 mg IMI) administered by ambulance paramedics in the prehospital management of heroin overdose. ⋯ The concurrent use of alcohol with heroin resulted in the use of greater than standard doses of naloxone by paramedics in resuscitating overdose patients. It is possible that the higher dose of naloxone is required to reverse the combined effects of alcohol and heroin. There was also a link between initial patient presentation and the dose of naloxone required for resuscitation. In light of these findings, it would appear that initial patient presentation and evidence of alcohol use might be useful guides as to providing the most effective dose of naloxone in the prehospital setting.
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Clinical Trial
Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans.
Previous studies have shown that a single dose of methylnaltrexone, a unique peripheral opioid antagonist, reverses opioid-induced gut hypomotility in humans. Because repeated drug doses are likely to be needed to treat patients with opioid-induced or postsurgical bowel dysfunction, the authors have now examined the safety, pharmacological activity, and pharmacokinetics of a multiple-dose regimen of methylnaltrexone, administered as 12 consecutive intravenous doses (0.3 mg/kg every 6 hours) in 12 healthy subjects. Steady state was achieved rapidly, and after repeated dosing for 3 days, methylnaltrexone decreased oral-cecal transit time from a pretreatment baseline value of 101.3 +/- 29.4 min (mean +/- SD) to 82.5 +/- 20.7 min. ⋯ There was essentially no accumulation of methylnaltrexone, based on the ratio of AUC values after doses 12 and 1. This study showed that repeated administration of intravenous methylnaltrexone is well tolerated in humans, with no significant adverse events or changes in opioid subjective ratings and no clinically noteworthy alterations in pharmacokinetics. The observation of a significant reduction in the gut transit time after repeated administration of methylnaltrexone to these opioid-naive volunteers suggests that endogenous opioids modulate human gut motility.