Articles: narcotic-antagonists.
-
Palliative medicine · Apr 1996
Randomized Controlled Trial Clinical TrialAn investigation of the ability of oral naloxone to correct opioid-related constipation in patients with advanced cancer.
A dose-ranging study of the use of oral naloxone in opioid-related constipation in patients with far-advanced cancer is reported. Naloxone doses were calculated as a percentage of the morphine dose each patient was receiving. Seventeen patients entered the first phase of the study, which had a randomised, double-blind design. ⋯ It is concluded that oral naloxone at a daily dose of 20% or more of the prevailing 24 h morphine dose is a potentially valuable therapy for opioid-related constipation. However, opioid withdrawal was observed and it is suggested that initial individual naloxone doses should not exceed 5 mg. Further research is needed into the oral absorption of naloxone, as well as further studies of clinical efficacy and dosing.
-
J. Pharmacol. Exp. Ther. · Apr 1996
Effects of naloxone and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 and the protein kinase inhibitors H7 and H8 on acute morphine dependence and antinociceptive tolerance in mice.
Previous studies measuring opioid inhibition of cyclic adenosine monophosphate in SH-SY5Y cells supported the hypothesis that continuous agonist stimulation causes a gradual conversion of the mu opioid receptor to a sensitized or constitutively active state termed mu*. Conversion to mu* was prevented by the kinase inhibitor H7, but not its close analog H8. Naloxone was proposed to act as a negative antagonist (inverse agonist) blocking mu* activity, whereas D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) appeared to act as a neutral antagonist having no effect on mu* activity. ⋯ Morphine pretreatment (100 mg/kg, s.c., -5 hr) produced antinociceptive tolerance as shown by a 2.7-fold increase in the calculated morphine A50 value. Tolerance was reversed by H7, but not H8, treatment (50 nmol, i.c.v., -30 min). These results are consistent with the hypothesis that a sensitized or constitutively active mu* state plays a role in narcotic tolerance and dependence.
-
Anesthesia and analgesia · Mar 1996
Randomized Controlled Trial Comparative Study Clinical TrialNaloxone versus nalbuphine infusion for prophylaxis of epidural morphine-induced pruritus.
This randomized, double-blind study compared the efficacy of two mu-receptor antagonists, naloxone and nalbuphine, in the prophylactic management of pruritus in postcesarean section patients receiving epidural morphine. Dosages of study drugs were individualized by the use of a patient self-administration (PSA) device. All 51 patients were healthy women who received a uniform epidural anesthetic and epidural morphine (5 mg). ⋯ The potency ratio for naloxone:nalbuphine for antagonism of the pruritic effects of epidural morphine was approximately 40:1. Intervention to treat either unrelieved pruritus or pain, respectively, was necessary in the following numbers of patients: Group A, 0/1; Group B, 1/1; Group C, 2/2. Prophylactic infusions offer the potential for labor cost savings by minimizing the need for episodic therapeutic interventions to treat pruritus.
-
Randomized Controlled Trial Clinical Trial
The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia.
Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in understanding the mechanisms underlying placebo response. In the present study, we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain. First, we found that part of the placebo response was reversed by naloxone, confirming previous studies on the role of opioids in the placebo phenomenon. ⋯ The placebo effect can thus be modulated in two opposite directions: it can be partially abolished by naloxone and potentiated by proglumide. The fact that placebo potentiation by proglumide occurred only in placebo responders, but not in non-responders, suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide. These results suggest an inhibitory role for cholecystokinin in placebo response, although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms.
-
J Clin Psychopharmacol · Feb 1996
Randomized Controlled Trial Comparative Study Clinical TrialBuprenorphine versus methadone in the treatment of opioid dependence: self-reports, urinalysis, and addiction severity index.
This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharmacotherapy, treatment during the clinical trial included individual counseling, weekly group therapy, and on-site medical services. Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning, as assessed by the Addiction Severity Index, rates of urinalysis tests positive for opioids, and self-reports of opioid withdrawal symptoms, illicit opioid use, and cocaine use. ⋯ A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group. These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone. In addition, these results demonstrate the benefits of drug abuse treatment, both for drug and alcohol use and in other areas of psychosocial functioning.