Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of two different doses of oral naltrexone on the adverse effects and the analgesia associated with intrathecal morphine was compared in a double-blind, placebo-controlled study. Thirty-five patients undergoing cesarean section were provided postoperative analgesia by 0.25 mg intrathecal morphine. Sixty minutes later they were given 6 mg naltrexone, 3 mg naltrexone, or placebo as an oral solution. Pain relief was assessed by the Visual Analog Scale. Requirements for additional analgesics and side effects were recorded. Duration of analgesia was shorter in the 3- and 6-mg naltrexone groups than in the placebo group, 10.0 +/- 2.6, 12.4 +/- 2.6, and 19.2 +/- 4.5 h (mean +/- SEM), respectively, but values did not reach statistical significance. The incidence of pruritus and vomiting was significantly less in the 6-mg naltrexone group than in the other two groups (P less than 0.05). Somnolence was significantly less in the 3- and 6-mg naltrexone groups than in the placebo group (P less than 0.05). Naltrexone (6 mg) is an effective oral prophylactic against the pruritus and vomiting associated with intrathecal morphine for analgesia after cesarean section, but it is associated with shorter duration of analgesia.
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PMID:Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. 220 28

Naltrexone, an opioid antagonist recently advocated for the control of stereotypic behavioral patterns in horses and dogs, induced an intense dose-related pruritic reaction in a dog with tail-chasing and self-mutilating behavior. Used in human beings primarily as an adjunct in the treatment of opioid abusers, naltrexone's adverse effects include dermatologic signs, such as alopecia and pruritus, observed in < 1% of human patients. In contrast to previously reported findings, naltrexone treatment was of limited benefit to the dog of this report. During administration of the drug, stereotypic patterns were reduced but did not disappear. Although naltrexone may be effective in controlling certain obsessive-compulsive disorders, its inconsistent therapeutic value, prohibitive cost to pet owners, and side effects such as the pruritus observed in the dog of this report may restrict use of this drug.
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PMID:Naltrexone-induced pruritus in a dog with tail-chasing behavior. 842 34

Itching is a well known side-effect of opiate therapy. To gain insight into the possible contribution of opiate receptors to itching we compared the antipruritic effect of naltrexone (Nemexin), an opiate antagonist, to an H1-receptor antagonist and to placebo. In a double blind cross-over study on 15 healthy volunteers, 25 mg naltrexone or placebo was orally given 60 min prior to a histamine stimulus. In a second, otherwise identical experiment, 10 mg cetirizine, an H1 blocker, or placebo was orally given 12 h before the experiment to the same group of volunteers. Histamine was applied iontophoretically to the forearm skin and the following parameters were assessed thereafter: weal and flare size, itch intensity and the extension of the area of alloknesis ('itchy skin') around the application site. Naltrexone had no effect on the vascular histamine reactions 'weal' and 'flare', whereas cetirizine abolished the weal reactions and greatly diminished the flare reactions. Both naltrexone and cetirizine significantly diminished histamine induced itching. In contrast to placebo and cetirizine, naltrexone abolished alloknesis completely in four of 15 volunteers and in the others alloknesis was greatly reduced after naltrexone. Since vascular reactions to histamine are of peripheral origin, whereas alloknesis depends on central nervous mechanisms, our findings suggest a pronounced centrally mediated action of naltrexone on histamine induced pruritus.
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PMID:Opiate and H1 antagonist effects on histamine induced pruritus and alloknesis. 941 11

Intense, generalized pruritus associated with mycosis fungoides was relieved using subcutaneous naloxone but intensified when changed to the new oral opioid antagonist, naltrexone. Rechallenge again led to worsening in pruritus. This unexpected adverse effect is surprising as naltrexone and naloxone are currently thought to work via similar opioid receptor binding. The worsening of the itch may have been due to adaptation in opioid receptor expression induced by prolonged naloxone therapy, possibly highlighting differential opioid receptor affinity between naltrexone and naloxone, or may have represented an idiosyncratic adverse reaction. Naltrexone and naloxone have been reported to reduce pruritus due to cholestasis, uraemia, morphine epidurals, and possibly atopic dermatitis and urticaria. Naltrexone has the convenience of oral administration and a longer half-life. The role of the opioid system and naltrexone in pruritus is reviewed.
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PMID:Naltrexone: a case report of pruritus from an antipruritic. 943 14

Renal itch is localized or generalized itch, affecting patients with chronic renal failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. It does not result from raised serum urea levels. The prevalence of renal itch has increased with the growing population in chronic renal failure and is a considerable cause of morbidity. The prevalence of itch increases with deteriorating renal function but does not improve significantly with dialysis. The pruritus is independent of duration of dialysis or cause of renal failure. The aetiology of renal itch is unclear. There is little evidence of a major role for histamine and antihistamines are rarely beneficial. Hyperparathyroidism, abnormal cutaneous innervation and endogenous opioids have been postulated as contributory factors. Treatment of renal itch is difficult. Naltrexone, oral activated charcoal, UVB phototherapy and ondansetron have been shown to be effective. Topical capsaicin may be of benefit in patients with localized pruritus. The definitive treatment for renal itch remains renal transplantation.
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PMID:Renal itch. 1073 30

A simple, sensitive, selective and reliable reversed-phase high-performance liquid chromatographic (HPLC) method with UV detection is described for the determination of naltrexone in plasma samples. Naltrexone and the internal standard, naloxone, were isolated from plasma either with a liquid-liquid extraction method using ethyl acetate or with a solid-phase extraction method using Sep-Pack C18 cartridge before chromatography. The extracts were dried under a stream of nitrogen and the samples were reconstituted in the mobile phase, then 20 microL were injected on a Waters Symmetry C18 column (5 microm particle size, 4.6 x 150 mm). The mobile phase consisted of 0.06% triethylamine (pH 2.8)-acetonitrile (92:8, v/v) pumped at 1 mL/min. The peak-area ratio versus plasma concentration was linear over the range of 10-500 ng/mL and the detection limit was less than 8 ng/mL. Quantification was by ultra-violet detection at 204 nm. The present method was applied to the determination of the plasma concentration of naltrexone in dialyzed patients. Patients (n = 8) with severe generalized pruritus received 50 mg of naltrexone orally per day for 2 weeks. The variability in the therapeutic response in treated patients required plasma concentration investigations of this opioid antagonist.
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PMID:High-performance liquid chromatographic determination of naltrexone in plasma of hemodialysis patients. 1085 Jun 17

Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.
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PMID:Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema. 1236 98

6beta-Naltrexol is the major metabolite of the opioid receptor antagonist, naltrexone, in humans. However, there are no functional studies of 6beta-naltrexol in primates. The aim of this study was to compare the in vitro and in vivo potencies of naltrexone and 6beta-naltrexol in rhesus monkeys. Affinity and potency were determined using radioligand displacement and stimulation of 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in monkey brain membranes. In vivo apparent pA(2) analysis was applied to compare the mu-opioid receptor (MOR) antagonist potency of both compounds in nondependent monkeys. In addition, the potencies of both compounds were determined in precipitating withdrawal manifested by increased respiratory parameters in acute morphine-dependent monkeys. In vitro assays revealed that naltrexone displayed 2-fold higher affinity and potency than 6beta-naltrexol for the MOR binding site and for MOR agonist-stimulated [(35)S]GTPgammaS binding, respectively. 6beta-Naltrexol (0.32-3.2 mg/kg) dose-dependently produced parallel rightward shifts of the dose-response curve of alfentanil-induced antinociception. Nevertheless, the apparent pA(2) value of 6beta-naltrexol (6.5) was 100-fold less potent than that of naltrexone (8.5) determined previously. 6beta-Naltrexol was also less potent than naltrexone in antagonizing other MOR-mediated effects including respiratory depression and itch/scratching. Naltrexone (0.0032-0.032 mg/kg) and 6beta-naltrexol (0.32-3.2 mg/kg) retained the same potency difference in precipitating withdrawal to a similar degree. Furthermore, 6beta-naltrexol failed to block naltrexone-precipitated withdrawal in morphine-dependent monkeys. These results indicate that naltrexone and 6beta-naltrexol display similar pharmacological actions with a large in vivo potency difference in monkeys such that 6beta-naltrexol may play a minimal role in the therapeutic or antagonist effects of naltrexone in primates.
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PMID:Differential in vivo potencies of naltrexone and 6beta-naltrexol in the monkey. 1625 20

Generalized pruritus secondary to cholestasis is a difficult dermatologic condition to treat. We present a case of a 17-month-old child with congenital biliary atresia with generalized pruritus refractory to treatment with oral antihistamines, topical steroids, cholestyramine, and rifampin but improved remarkably with the addition of naltrexone. Naltrexone is a well-tolerated medication with little adverse effects. We believe that naltrexone may be an effective adjuvant treatment in the management of cholestatic pruritus in the pediatric population.
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PMID:The use of naltrexone in the management of severe generalized pruritus in biliary atresia: report of a case. 1857 62

Protease-activated receptor (PAR)-2 and PAR-4 are implicated in nonhistaminergic itch. We investigated dose dependence, tachyphylaxis, and cross-tachyphylaxis of itch-associated scratching elicited by intradermal injections of PAR-2 and PAR-4 agonists, serotonin (5-hydroxytryptamine, 5-HT), and histamine in ICR mice, as well as mu-opioid modulation of PAR-2 agonist-evoked scratching. Each agent elicited dose-related increases in scratch bouts. Scratching elicited by the PAR-4 agonist and histamine both exhibited significant tachyphylaxis but no cross-tachyphylaxis with each other. Scratching evoked by 5-HT did not exhibit significant tachyphylaxis but did exhibit significant cross-tachyphylaxis to scratching evoked by the PAR-2 and PAR-4 agonists and histamine. Naltrexone and high-dose morphine (10 mg/kg) attenuated PAR-2 agonist-evoked scratching, whereas lower dose morphine (1 mg/kg) had no effect. High-dose morphine also significantly increased circling behavior, which may have interfered with scratching. The PAR-2 agonist and 5-HT produced overlapping distributions of Fos-like immunoreactivity in the superficial dorsal horn. These results indicate that PAR-2 and PAR-4 agonists, histamine, and 5-HT elicit itch-related scratching and activate superficial dorsal horn neurons that may participate in scratch reflex and ascending itch signaling pathways.
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PMID:Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice. 1929 90


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