Articles: narcotic-antagonists.
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Letter Case Reports
Tramadol overdose requiring prolonged opioid antagonism.
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Almost all patients treated with opioids suffer from constipation. Numerous laxatives are used to overcome the problem, but none has yet been found to yield favourable results in all patients. Several studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impairment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied. ⋯ The medical history of the 3 patients in whom naloxone failed to abolish constipation revealed neurological disturbances. Treatment of these patients included the use of neuroleptics, antiemetics, and other drugs. In this context, it should be noted that oral naloxone can be expected to abolish only opioid-induced constipation. In conclusion, it was found that the treatment of opioid-induced constipation by administration of oral naloxone produced positive results. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.
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Clin. Pharmacol. Ther. · Jan 1997
Effects of liver disease on the disposition of the opioid antagonist nalmefene.
The pharmacokinetics of nalmefene and its glucuronide metabolite were investigated in 12 patients with liver disease (four patients with mild, five patients with moderate, and three patients with severe liver disease) and 12 age-, weight-, and gender-matched control subjects. ⋯ The clearance of nalmefene was significantly reduced in the presence of liver disease. However, because nalmefene will be primarily used in the acute care setting for reversal of opioid-induced effects, it is not likely that these alterations will necessitate a dosage modification.
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The opioid antagonist, naloxone, produces equivocal effects on the magnitude of nociceptive responses in several animal models of persistent pain, including the formalin test. Hindpaw injection of dilute formalin produces not only inflammation but also phasic (Phase 1) and persistent (Phase 2) behavioral and cardiovascular nociceptive responses in the rat. ⋯ Although the 100 mg/kg per h dose significantly decreased these responses, it also produced muscle rigidity and profound bradycardia. We conclude that endogenous opioids do not significantly modulate the nociceptive processing induced by subcutaneous formalin.
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Randomized Controlled Trial Clinical Trial
Safety and tolerance of methylnaltrexone in healthy humans: a randomized, placebo-controlled, intravenous, ascending-dose, pharmacokinetic study.
N-methylnaltrexone bromide (methylnaltrexone) is a quaternary opioid antagonist with a limited ability to cross the blood-brain barrier. In animal models it reverses at peripheral receptors such side effects of opioids as decreased gastrointestinal motility, emesis, and cough suppression without affecting the desired analgesic effect mediated by central nervous system receptors. Methylnaltrexone thus may be a clinically useful compound for the prevention and treatment of opioid-induced side effects. ⋯ There were no significant subjective changes, no release of histamine, and no changes in physical examination or laboratory studies during the course of the study. Pharmacokinetic analysis revealed an elimination half-life of 117.5 minutes (+/-53.2), and a clearance of 38.8 L/hr (+/-17.4) with a methylnaltrexone dose of 0.64 mg/kg. Our results indicate that methylnaltrexone is well tolerated at doses of 0.32 mg/kg in healthy humans.