naloxone and Nausea

Topics: Adult; Analgesics, Opioid; Chronic Pain; Constipation; Delayed-Action Preparations; Diarrhea; Drug Combinations; Gastrointestinal Tract; Humans; Naloxone; Nausea; Neoplasms; Oxycodone

To evaluate the effects of naloxone on opioid-induced side effects, the present meta-analysis was constructed.. Electronic databases including PubMed, EMBASE, and CNKI (China National Knowledge Internet) were used for literature search. Studies on comparison of opioid-side effects between naloxone-treated group and placebo or normal saline-related group were included in the meta-analysis. Heterogeneity analysis was performed with Chi-square and I test. Pooled analysis was based on fixed-effects model, if heterogeneity between the eligible studies was negligible (I < 50%, P > 0.05), otherwise, random-effects model was used. Sensitivity analysis was applied to assess the robustness of the results and publication bias was evaluated by Begg and Egger test.. Thirteen studies including 1138 patients were included in the meta-analysis. Pooled analysis indicated that naloxone could significantly reduce the occurrence of pruritus (RR [risk ratio] = 0.252, 95% CI [confidence interval] = 0.137-0.464), nausea (RR = 0.323, 95% CI = 0.245-0.428), and vomiting (RR = 0.338, 95% CI = 0.192-0.593) which were induced by opioids. However, naloxone did not relieve pain (standardized mean difference [SMD] = -0.052, 95% CI = -0.453 to 0.348) and somnolence (RR = 0.561, 95% CI = 0.287 to 1.097) in patients received opioid treatment. Additionally, there were no significant publication bias between the included studies (Begg test, P = 0.602; Egger test, P = 0.388).. Addition of naloxone might act as an effective treatment for prophylaxis of opioid-induced pruritus, nausea, and vomiting in clinical practice.

Topics: Humans; Naloxone; Narcotic Antagonists; Nausea; Opioid-Related Disorders; Pruritus; Randomized Controlled Trials as Topic

The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients' daily functioning.. Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments.. Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, -5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies.. Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.

Topics: Chronic Pain; Constipation; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Headache; Humans; Naloxone; Nausea; Oxycodone; Phenols; Quality of Life; Tapentadol; Vomiting

Forty cancer patients were randomly assigned to two groups (n = 20). All had incapacitating pain unresponsive to the usual non opioid analgesic drugs. An epidural catheter was set up at the level of the most painful metamere, and made to pass subcutaneously so as to exit either in the supraclacicular fossa, or on the patient's flank. At T0, the patients were given 4 mg morphine hydrochloride diluted in 10 ml normal saline. Thirty min later, patients in the naloxone group (group N) were given a 0.4 mg bolus, followed by a constant rate infusion of 5 micrograms.kg-1.h-1, of naloxone hydrochloride during 18 h. Patients in group P (placebo) were given normal saline instead. The degree of pain was studied with a visual analogue scale and analgesia was assessed by a clinician on a five point scale. These two parameters were obtained half an hour after the injection of morphine and 2, 4, 6 and 24 hours later. At the same time, the patients were questioned about adverse side-effects: nausea, vomiting, pruritus, dysuria, urinary retention. Respiratory depression was assessed clinically and biologically (blood gas measurements at the afore mentioned times). Heart rate, systolic and diastolic blood pressure were also measured. There was no statistically significant difference between the groups in quality and duration of analgesia. Pain reached its lowest level 4 h after the injection of morphine, returning to half its original value at the 24th h. This was also true for the incidence of nausea (11 in group N, 5 in group P), vomiting (3 in both groups), and urinary retention (6 in group P, 5 in group N).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Analgesia, Epidural; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Nausea; Neoplasms; Pain; Pain Measurement; Pruritus; Respiration Disorders; Urinary Retention; Vomiting

Chemotherapy-induced nausea and vomiting are primarily regulated by chemoreceptor trigger zone (CTZ)-vomiting center (VC) pathways. Dopaminergic (D2), histaminic (H1), and muscarinic cholinergic (Ach) receptors are present in these sites, and specific receptor antagonists are potent but not "universal" antiemetics when used alone or in combination. Recently, neurons containing the endogenous opiate enkephalin were also identified near the CTZ and the VC. Furthermore, opiates stimulate vomiting at the CTZ and inhibit vomiting at the VC in dogs and in cats. A dose-related increase in nausea and vomiting in response to the opiate antagonist naloxone has also been demonstrated in patients receiving cancer chemotherapy. These observations support a role for endogenous opiates in regulating chemotherapy-induced nausea and vomiting; further, they suggest that narcotic agents may be effective antiemetics in this setting.

Topics: Antineoplastic Agents; Chemoreceptor Cells; Child; Endorphins; Humans; Naloxone; Nausea; Neoplasms; Vomiting

Butorphanol (Stadol) is a synthetic agonist-antagonist analgesic from the 14-hydroxymorphinan series. Animal studies display analgesia, antitussive effects, low gastrointestinal activity, limited respiratory depression, some cardiovascular and skeletal muscle actions, diuresis, slight miosis and opiate antagonism. Butorphanol is metabolized in the liver with renal excretion, yielding a half-life of 3-4 h. Pain relief is good to excellent with parenteral administration in 90% of patients with moderate to severe pain. Surgical anesthetic indications involve preoperative and preinduction supplementation, balanced anesthesia and postoperative pain. Side effects are sedation, nausea, elevated pulmonary vascular pressures and rarely CNS excitation. Limited respiratory depression exists. Butorphanol is a potent analgesic agent with a favorable side effect profile.

Topics: Anesthesia; Animals; Antitussive Agents; Butorphanol; Chemical Phenomena; Chemistry; Depression, Chemical; Diuretics; Dose-Response Relationship, Drug; Humans; Morphinans; Morphine; Naloxone; Nausea; Oxymorphone; Pain; Pulmonary Wedge Pressure; Rats; Respiration; Substance-Related Disorders

A prolonged-release formulation of oxycodone/naloxone has been shown to be effective in European populations for the management of chronic moderate to severe pain. However, no clinical data exist for its use in Korean patients. The objective of this study was to assess efficacy and safety of prolonged-release oxycodone/naloxone in Korean patients for management of chronic moderate-to-severe pain.. In this multicenter, single-arm, open-label, phase IV study, Korean adults with moderate-to-severe spinal disorder-related pain that was not satisfactorily controlled with weak opioids and nonsteroidal anti-inflammatory drugs received prolonged-release oral oxycodone/naloxone at a starting dose of 10/5 mg/day (maximum 80/40 mg/day) for 8 weeks. Changes in pain intensity and quality of life (QoL) were measured using a numeric rating scale (NRS, 0-10) and the Korean-language EuroQol-five dimensions questionnaire, respectively.. Among 209 patients assessed for efficacy, the mean NRS pain score was reduced by 25.9% between baseline and week 8 of treatment (. Prolonged-release oxycodone/naloxone provided significant and clinically relevant reductions in pain intensity and improved QoL in Korean patients with chronic spinal disorders. (ClinicalTrials.gov identifier: NCT01811238).

Topics: Aged; Analgesics, Opioid; Back Pain; Chronic Pain; Constipation; Delayed-Action Preparations; Dizziness; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Naloxone; Nausea; Oxycodone; Pain Measurement; Quality of Life; Republic of Korea; Severity of Illness Index; Spinal Diseases

Opioid-induced side effects, such as pruritus, nausea, and vomiting are common and may be more debilitating than pain itself. A continuous low-dose naloxone infusion (0.25 μg/kg/h) ameliorates some of these side effects in many but not all patients without adversely affecting analgesia. We sought to determine the optimal dose of naloxone required to minimize opioid-induced side effects and to measure plasma morphine and naloxone levels in a dose escalation study.. Fifty-nine pediatric patients (24 male/35 female; average age 14.2 ± 2.2 years) experiencing moderate to severe postoperative pain were started on IV patient-controlled analgesia morphine (basal infusion 20 μg/kg/h, demand dose 20 μg/kg, 5 doses/h) and a low-dose naloxone infusion (initial cohort: 0.05 μg/kg/h; subsequent cohorts: 0.10, 0.15, 0.25, 0.40, 0.65, 1, and 1.65 μg/kg/h). If 2 patients developed intolerable nausea, vomiting, or pruritus, the naloxone infusion was increased for subsequent patients. Dose/treatment success occurred when 10 patients had minimal side effects at a naloxone dose. Blood samples were obtained for measurement of plasma morphine and naloxone levels after initiation of the naloxone infusion, processed, stored, and measured by tandem mass spectrometry with electrospray positive ionization.. The minimum naloxone dose at which patients were successfully treated with a <10% side effect/failure rate was 1 μg/kg/h; cohort size varied between 4 and 11 patients. Naloxone was more effective in preventing pruritus than nausea and vomiting. Concomitant use of supplemental medicines to treat opioid-induced side effects was required at all naloxone infusion rates. Plasma naloxone levels were below the level of assay quantification (0.1 ng/mL) for infusion rates ≤0.15 μg/kg/h. At rates >0.25 μg/kg/h, plasma levels increased linearly with increasing infusion rate. In each dose cohort, patients who failed therapy had comparable or higher plasma naloxone levels than those levels measured in patients who did not fail treatment. Plasma morphine levels ranged between 3.52 and 172 ng/mL, and >90% of levels ranged between 10.2 and 61.6 ng/mL. Plasma morphine levels were comparable between patients who failed therapy and those patients who achieved symptom control.. Naloxone infusion rates ≥1 μg/kg/h significantly reduced, but did not eliminate, the incidence of opioid-induced side effects in postoperative pediatric patients receiving IV patient-controlled analgesia morphine. Patients who failed therapy generally had plasma naloxone and morphine levels that were comparable to those who had good symptom relief suggesting that success or failure to ameliorate opioid-induced side effects was unrelated to plasma levels.

Topics: Adolescent; Analgesia, Patient-Controlled; Analgesics, Opioid; Antiemetics; Antipruritics; Baltimore; Child; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Nausea; Odds Ratio; Pain Measurement; Pain, Postoperative; Prospective Studies; Pruritus; Regression Analysis; Severity of Illness Index; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Vomiting

Early studies showed that naloxone infusion decreases the incidence of morphine-related side effects from intravenous patient-controlled analgesia. This study aimed to determine whether naloxone preserved analgesia while minimizing side effects caused by intravenous tramadol administration.. Eighty patients undergoing general anesthesia for cervical vertebrae surgery were randomly divided into four groups. All patients received 1 mg/kg tramadol 30 minutes before the end of surgery, followed by a continuous infusion with 0.3 mg x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(-1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20). Visual analog scales (VAS) for pain during rest and cough, nausea five-point scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia and side effects were evaluated by blinded observers.. Seventy-eight patients were included in this study. The intravenous tramadol administration provided the satisfied analgesia. There was no significant difference in either resting or coughing VAS scores among naloxone groups and control group. Compared with control group, sedation was less in groups II, III, and IV at 6, 12, and 24 hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6, 12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P < 0.01).. A small-dose naloxone infusion could reduce tramadol induced side effects without reversing its analgesic effects.

Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Anesthesia, General; Cervical Vertebrae; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Narcotic Antagonists; Nausea; Tramadol

Patients with sickle cell disease experience painful crises that often require hospitalization for a continuous infusion of morphine that may cause significant pruritus. We conducted a pilot study to determine the feasibility of simultaneous continuous co-infusion of naloxone with morphine, test novel assessment instruments for pruritus, and explore whether pruritus could be reduced while maintaining effective analgesia. Patients with sickle cell disease and painful crisis requiring continuous infusion morphine received continuous co-infusion of naloxone at 0.25 (low dose) or 1.0 mcg/kg x hr (high dose). Pain scores were obtained using the FACES scale and a 100-mm visual analog scale (VAS). Itching was quantified by a modified VAS score. Evaluable data were obtained on 16 patients. Simultaneous co-infusion of naloxone and morphine was feasible, did not seem to reduce the analgesic efficacy of morphine, and was associated with no adverse effects. The high dose group reported a lower median "VAS worst itch" score than the low dose group (4.8 vs. 7.3, P = 0.08). Simultaneous continuous infusion of naloxone with morphine in pediatric patients with sickle cell disease and pain crisis was feasible and well tolerated. A quantitative pruritus score allowed us to systematically measure pruritus. Further evaluation by randomized, placebo-controlled study of 1 mcg/kg x hr naloxone in this setting is required.

Topics: Adolescent; Anemia, Sickle Cell; Child; Drug Therapy, Combination; Female; Humans; Hyperalgesia; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nausea; Pain; Pain Measurement; Pilot Projects; Pruritus; Vomiting

We compared the effects of systemic morphine on normal (heat and cold) pain and paradoxical burning pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin. Twelve healthy volunteers participated in a randomised, double-blind, cross-over study to compare the effects of intravenous administration of morphine (0.025 or 0.1mg/kg) or placebo (saline). Stimuli were applied to the palm of the right hand with a thermode ("thermal grill") composed of six bars, whose temperatures were controlled by Peltier elements. For each session, we measured the heat and cold pain thresholds and then successively measured the intensity of: (i) paradoxical pain evoked by a combination of non-noxious warm and cold stimuli; (ii) "normal" pain evoked by suprathreshold heat or cold stimuli; (iii) non-painful sensations evoked by warm or cold stimuli at temperatures used to produce paradoxical pain. Measurements were performed before 20min after the administration of morphine or placebo and 5min after the administration of the morphine antagonist, naloxone. The administration of 0.1mg/kg of morphine, but not 0.025mg/kg, induced a significant and naloxone-reversible reduction of paradoxical pain intensity, which was directly correlated with the reduction of normal cold pain. No differences were observed for non-painful thermal sensations. The paradoxical burning pain evoked by a thermal grill can be modified pharmacologically by analgesics and share some mechanisms with normal pain. This unique experimental "illusion of pain" may represent a new model to test analgesics in healthy volunteers.

Topics: Adult; Cold Temperature; Cross-Over Studies; Double-Blind Method; Female; Hand; Hot Temperature; Humans; Illusions; Injections, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nausea; Pain; Pain Measurement; Pain Threshold; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Young Adult

There is an increasing body of evidence supporting the need for prophylactic management of the adverse events (AEs) associated with long-term opioid use in patients with chronic pain. Symptoms of bowel dysfunction, such as constipation, may have a significant impact on a patient's quality of life and willingness to continue opioid therapy, and therefore should be managed proactively to ensure that the patient can continue effective pain management. The fixed-dose combination (FDC) prolonged-release (PR) oxycodone/naloxone (OXN) may be an effective therapeutic approach to delivering analgesia, with a reduced risk for opioid-induced constipation.. The aim of this paper was to report the pharmacokinetic results from a single-dose study and a multiple-dose bioequivalence study of OXN versus separate formulations of oxycodone PR and naloxone PR administered concurrently in healthy subjects.. Both studies were open-label, randomized crossover studies in healthy adult male and female subjects. In the single-dose study, subjects were randomly assigned to 1 of 4 treatment groups: OXN FDC (44 x 10/55-mg, 2 x 20/110-mg, or 1 x 40/20-mg dose strength [each given at a total combined dose of 40/220 mg]) or oxycodone PR 40 mg + naloxone PR 20 mg given in separate formulations. In the multiple-dose study, 34 subjects were randomly assigned to 1 of 3 treatment groups: OXN FDC 40/20 mg, oxycodone PR 40 mg, or naloxone PR 20 mg. Treatments were considered bioequivalent if the 90% CIs for relative bioavailability calculations fell within a predetermined range of 80% to 125%. AEs were assessed by the investigator at each study visit.. The single-dose study included 28 subjects (22 men, 6 women; mean [SD] age, 32.3 [5.44] years; weight, 75.5 [9.3] kg; and body mass index [BMI], 24.2 [2.5] kg/mm(2)). The mean plasma oxycodone concentration-time curves for OXN and oxycodone PR + naloxone PR were similar. With oxycodone, the mean (SD) AUC(t) values with OXN 10/5, 20/10, and 40/20 mg and oxycodone PR + naloxone PR were 473.49 (72.16), 491.22 (82.18), 488.89 (91.04), and 502.28 (84.13) ng . h/mL, respectively; mean C(max) values were 34.91 (4.36), 35.73 (4.93), 34.46 (5.03), and 40.45 (4.71) ng/mL. For naloxone-3-glucuronide (the primary analyte of naloxone), the mean (SD) AUC(t) values with OXN 10/5, 20/10, and 40/20 mg and oxycodone PR + naloxone PR were 539.93 (142.24), 522.45 (128.57), 520.10 (133.18), and 523.37 (119.75) ng . h/mL, respectively; mean C(max) values were 62.01 (15.96), 63.62 (19.51), 61.95 (18.37), and 63.55 (16.75) ng/mL. There were no statistically significant differences between the treatments, and each of the treatment comparisons resulted in 90% CIs within the range for bioequivalence. The multiple-dose steady-state bioequivalence study included 34 subjects (28 men, 6 women; mean [SD] age, 36 [9.4] years; weight,78.9 [11.7] kg; and BMI, 24.6 [1.9] kg/m(2)). No significant differences were observed between the treatments, with the exception of naloxone-3-glucuronide C(min,ss) values. Mean C(min,ss) values of 22.6 and 24.0 ng/mL were obtained for the OXN combination and naloxone PR tablet, respectively. In the multiple-dose study, the most frequently reported AEs with OXN,oxycodone PR, and naloxone PR were headache (7%, 26%, and 17%, respectively), anorexia (10%, 16%, and 13%), and nausea (10%, 13%, and 7%).. The results from the single-dose study were consistent with the regulatory definition of bioequivalence of the FDCs and single components across the range of doses administered. The pharmacokinetic properties of the OXN FDC were similar to those of oxycodone PR + naloxone PR given as separate formulations, based on the regulatory definition. These findings were consistent with the results of the multiple-dose steady-state bioequivalence study. In this population of healthy volunteers, the pharmacokinetic properties of oxycodone apparently were not significantly influenced by administering oxycodone in a combination product, and the availability of naloxone-3-glucuronide from OXN was similar to that from the naloxone PR tablet. These findings suggest that the coadministration of oxycodone PR and naloxone PR in an FDC would not significantly affect the bioavailability of either of its constituents in these subjects.

Topics: Administration, Oral; Adult; Anorexia; Area Under Curve; Biological Availability; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Female; Half-Life; Headache; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Nausea; Oxycodone; Receptors, Opioid; Tablets; Therapeutic Equivalency

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.

Topics: Adult; Analgesics, Opioid; Buspirone; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Nausea; Pain; Respiratory Insufficiency; Serotonin 5-HT1 Receptor Agonists

We tested the hypothesis that low-dose naloxone delivered with intravenous (IV) bolus morphine to emergency department patients in pain would reduce nausea.. Randomized, double-blind, placebo-controlled trial. Patients receiving 0.10 mg/kg morphine IV bolus rated pain, nausea, and pruritus on 100-mm visual analog scales at enrollment and 20 minutes. Patients were randomized to 0.25 microg/kg naloxone or equal volume placebo administered with IV morphine.. One hundred thirty-one enrolled, 99 (76%) treated according to protocol with sufficient data for analysis. At 20 minutes the difference between groups (naloxone-placebo) was 1 mm (95% CI [confidence interval], -9 to 11) for nausea, 1 mm (95% CI, -3 to 3) for pruritus, 4% (95% CI, -1 to 9) for vomiting, and 0% (95% CI, -5 to 5) for rescue antiemetics. Pain was significantly reduced in both groups.. Addition of 0.25 microg/kg naloxone to bolus morphine does not improve nausea, pruritus, vomiting, or reduce use of rescue antiemetics when administered to emergency department patients in pain.

Topics: Adult; Analgesia; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Nausea; Pain Measurement; Prospective Studies; Pruritus; Treatment Outcome; Vomiting

Topics: Administration, Oral; Administration, Rectal; Adolescent; Adult; Aged; Arrhythmias, Cardiac; Colic; Constipation; Dizziness; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Hypotension; Infusions, Intravenous; Injections, Intravenous; Injections, Subcutaneous; Intubation, Gastrointestinal; Male; Middle Aged; Naloxone; Narcotic Antagonists; Nausea; Neostigmine; Parasympathomimetics; Retrospective Studies; Treatment Outcome

To determine whether epidural naloxone preserved analgesia while minimizing side effects caused by epidural morphine.. Eighty patients undergoing combined epidural and general anesthesia for hysterectomy were randomly assigned to one of four groups. All received 2 mg epidural morphine bolus one hour before the end of surgery and a continuous epidural infusion was started containing 4 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (Group 1, n = 20), 0.083 microg x kg(-1) x hr(-1) of naloxone (Group 2, n = 20), 0.125 microg x kg(-1) x hr(-1) of naloxone (Group 3, n = 20) or 0.167 microg x kg(-1) x hr(-1) of naloxone (Group 4, n = 20). Analgesia and side effects were evaluated by blinded observers.. The combination of epidural morphine and bupivacaine provided good analgesia. Eight hours after the end of surgery, the pain score in the group receiving the highest dose of naloxone was lower than in the control group (VAS 1.2 vs. 2.0, P<0.05) but there was less pruritus in the high-dose naloxone group (itching score 1.3 vs. 1.9, P<0.05). Pain scores were no different in any of the naloxone groups from the control group. Itching was less in both of the higher dose naloxone groups (P<0.05 at 8, 16, and 32 hours). The incidence of vomiting in the control group was 40% vs. 5% for high dose naloxone group (P<0.05).. Epidural naloxone reduced morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect.

Topics: Adult; Analgesia, Epidural; Analgesics, Opioid; Bupivacaine; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Nausea; Pruritus

The effects of naloxone on side effects provoked by apomorphine (APO) administration in patients with parkinsonian syndrome have been studied. The group under study included eight patients with Parkinson's disease and four with parkinsonism who received 100 micrograms/kg s.c. APO acutely to test dopaminergic responsiveness. All patients were treated with 20 mg domperidone tablets t.i.d. and then for 2 consecutive days (in double blind fashion) were given a 2-hour i.v. saline infusion alone or with naloxone (8 mg) starting 30 min before APO administration. In both groups, naloxone delayed the appearance of sleepiness, and reduced the intensity of yawning, sleepiness, nausea, and vomiting as compared with saline. These findings indicate a potential usefulness of naloxone and other opioid antagonists in preventing acute APO side effects.

Topics: Apomorphine; Double-Blind Method; Female; Humans; Male; Naloxone; Nausea; Parkinson Disease; Sleep Stages; Vomiting; Yawning

Forty cancer patients were randomly assigned to two groups (n = 20). All had incapacitating pain unresponsive to the usual non opioid analgesic drugs. An epidural catheter was set up at the level of the most painful metamere, and made to pass subcutaneously so as to exit either in the supraclacicular fossa, or on the patient's flank. At T0, the patients were given 4 mg morphine hydrochloride diluted in 10 ml normal saline. Thirty min later, patients in the naloxone group (group N) were given a 0.4 mg bolus, followed by a constant rate infusion of 5 micrograms.kg-1.h-1, of naloxone hydrochloride during 18 h. Patients in group P (placebo) were given normal saline instead. The degree of pain was studied with a visual analogue scale and analgesia was assessed by a clinician on a five point scale. These two parameters were obtained half an hour after the injection of morphine and 2, 4, 6 and 24 hours later. At the same time, the patients were questioned about adverse side-effects: nausea, vomiting, pruritus, dysuria, urinary retention. Respiratory depression was assessed clinically and biologically (blood gas measurements at the afore mentioned times). Heart rate, systolic and diastolic blood pressure were also measured. There was no statistically significant difference between the groups in quality and duration of analgesia. Pain reached its lowest level 4 h after the injection of morphine, returning to half its original value at the 24th h. This was also true for the incidence of nausea (11 in group N, 5 in group P), vomiting (3 in both groups), and urinary retention (6 in group P, 5 in group N).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Analgesia, Epidural; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Nausea; Neoplasms; Pain; Pain Measurement; Pruritus; Respiration Disorders; Urinary Retention; Vomiting

To evaluate the role of endogenous opiates in chemo-therapy-induced nausea and vomiting, the narcotic-antagonist naloxone was administered to six pediatric patients receiving cancer chemotherapy. Naloxone was administered by continuous intravenous (i.v.) infusion after randomized, double-blind controlled assignment at a dose of 0, 10 or 40 micrograms/kg/h for 12 h. Each patient was studied for four consecutive and identical courses of chemotherapy (eight courses for each naloxone dose or 24 courses in all). A dose-related increase in nausea (nausea score 2.5 +/- 2.24, 3.83 +/- 2.73, and 5.75 +/- 2.86/12 h, p = 0.003), vomiting (emetic events 6.0 +/- 7.50, 8.08 +/- 6.71, and 10.3 +/- 8.91/12 h, p = 0.035), and patient aversion (course preference rank 1.5 +/- 0.45, 2.83 +/- 1.17, and 3.25 +/- 0.42/4 courses, p = 0.014) was observed. The infusion of naloxone in the absence of chemotherapy was without effect. These results support a role for endogenous opiates in regulating chemotherapy-induced nausea and vomiting, and further suggest that narcotic agents may be effective antiemetics in this setting.

Topics: Adolescent; Antineoplastic Agents; Chemoreceptor Cells; Child; Child, Preschool; Clinical Trials as Topic; Drug Synergism; Endorphins; Female; Humans; Male; Naloxone; Nausea; Neoplasms; Random Allocation; Vomiting

In a double-blind sequential trial, the influence of transdermal electrical nerve stimulation (TENS) was studied in patients who were treated with total infusions of metoclopramide 3.5 mg/kg to counter the emetic action of cisplatin 60-90 mg/m2. Transdermal electrical nerve stimulation further reduced the emetic episodes in ten of 11 treatment pairs (2 alpha = .10). This effect was blocked by naloxone. More surprisingly, TENS reduced the incidence of extrapyramidal effects of metoclopramide (i.e., akathisia and dystonia). These effects may be explained by the involvement of central nervous and peripheral TENS-induced production of opioid neuromodulators. An alternate hypothesis is the stimulation of serotonergic mechanisms via neuromodulation by opioid peptides, or by involvement of both systems.

Topics: Adult; Aged; Cisplatin; Clinical Trials as Topic; Double-Blind Method; Electric Stimulation; Female; Humans; Male; Metoclopramide; Middle Aged; Naloxone; Nausea; Neoplasms; Random Allocation; Skin; Vomiting

Twelve male volunteers given apomorphine (20 micrograms/kg/hr) for 40 min by i.v. infusion had significant changes in growth hormone, prolactin, vasopressin, pulse rate, sedation and nausea. Naloxone, (20 mg i.v.) or placebo given in a double-blind manner 10 min before the end of the apomorphine infusion as a concealed bolus did not alter the effects of apomorphine. Vasopressin rise correlated significantly with nausea intensity. We conclude that acute opiate receptor blockade does not reverse most apomorphine effects.

Topics: Adolescent; Adult; Apomorphine; Arginine Vasopressin; Blood Pressure; Drug Interactions; Growth Hormone; Heart Rate; Humans; Male; Naloxone; Nausea; Prolactin; Receptors, Opioid

The effects of naloxone were studied in 82 patients undergoing intracranial surgery under general anaesthesia with fentanyl or phenoperidine. After the operation was finished the patients' alertness, sensitivity to pain, blood pressure, pulse rate, respiratory rate, tidal and minute volume were recorded parallel with arterial blood gas analyses prior to and immediately after the administration of varying amounts of naloxone i.v. in a single dose. These parameters were also repeatedly controlled for several hours in the postoperative period. The results show that a single i.v. naloxone dose of 1 mug/kg b.w. is effective in the rapid and definite reversal of the respiratory depression caused by the analgesics. This dose was neither correlated to the total amount of analgesics given, nor to the time period which elapsed between the last dose of the analgesic drug and the administration of naloxone. No side effects or complications were encountered when the indicated doses of naloxone were given. It is concluded that, even in a small single dose, naloxone effectively antagonises the respiratory depression caused by fentanyl and phenoperidine without totally eliminating the immediate postoperative analgesic effects of these agents.

Topics: Adolescent; Adult; Aged; Anesthesia, General; Blood Pressure; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Female; Fentanyl; Humans; Male; Middle Aged; Naloxone; Nausea; Neuroleptanalgesia; Neurosurgery; Partial Pressure; Phenoperidine; Pulse; Respiration; Shivering; Tidal Volume; Vomiting

The effects of intravenous naloxone on several of the actions of intravenous morphine (mean dose 30 mg/70 kg) were studied in six volunteer subjects. Naloxone produced a well defined reversal of the respiratory depression, analgesia, and miotic and subjective effects of the morphine. The agonist action of morphine outlasted the antagonist action of a single dose of naloxone. The effect of repeated doses of naloxone was also short-lived, but continuous infusions were effective in maintaining reversal.

Topics: Arousal; Blood Pressure; Carbon Dioxide; Catheterization; Constriction; Humans; Male; Morphine; Naloxone; Nausea; Pain; Pupil; Respiration

Acute naloxone-precipitated morphine withdrawal (MWD) produces a conditioned place aversion (CPA) in rats even after one or two exposures to high-dose (20 mg/kg, sc) morphine followed 24-h later by naloxone (1 mg/kg, sc). However, the somatic withdrawal reactions produced by acute naloxone-precipitated MWD in rats have not been investigated. A recently discovered fatty acid amide, N-oleoylglycine (OlGly), which has been suggested to act as a fatty acid amide hydrolase (FAAH) inhibitor and as a peroxisome proliferator-activated receptor alpha (PPARα) agonist, was previously shown to interfere with a naloxone-precipitated MWD-induced CPA in rats.. The aims of these studies were to examine the somatic withdrawal responses produced by acute naloxone-precipitated MWD and determine whether OlGly can also interfere with these responses.. Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight. OlGly (5 mg/kg, ip) interfered with naloxone-precipitated MWD-induced abdominal contractions, lying on belly, diarrhea and mouthing movements in male Sprague-Dawley rats, by both a cannabinoid 1 (CB. These results suggest that the aversive effects of acute naloxone-precipitated MWD reflect nausea, which is suppressed by OlGly.

Topics: Animals; Female; Glycine; Male; Medically Unexplained Symptoms; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Nausea; Oleic Acids; Rats; Rats, Sprague-Dawley; Shrews; Substance Withdrawal Syndrome

Topics: Acetaminophen; Adult; Buprenorphine; Cocaine-Related Disorders; Diagnosis, Differential; Diarrhea; Drug Combinations; Female; Humans; Illicit Drugs; Naloxone; Narcotic Antagonists; Nausea; Opioid-Related Disorders; Oxycodone; Substance Abuse Detection; Vomiting

An increasing and serious heroin overdose problem in Oslo has mandated the increasing out-of-hospital use of naloxone administered by paramedics. The aim of this study was to determine the frequencies and characteristics of adverse events related to this out-of-hospital administration by paramedics.. A one-year prospective observational study from February 1998 to January 1999 was performed in patients suspected to be acutely overdosed by an opioid. A total of 1192 episodes treated with naloxone administered by the Emergency Medical Service system in Oslo, were included. The main outcome variable was adverse events observed immediately after the administration of naloxone.. The mean age of patients included was 32.6 years, and 77% were men. Adverse events suspected to be related to naloxone treatment were reported in 45% of episodes. The most common adverse events were related to opioid withdrawal (33%) such as gastrointestinal disorders, aggressiveness, tachycardia, shivering, sweating and tremor. Cases of confusion/restlessness (32%) might be related either to opioid withdrawal or to the effect of the heroin in combination with other drugs. Headache and seizures (25%) were probably related to hypoxia. Most events were non-serious. In three episodes (0.3%) the patients were hospitalized because of adverse events.. Although adverse events were common among patients treated for opioid overdose in an out-of-hospital setting, serious complications were rare. Out-of-hospital naloxone treatment by paramedics seems to save several lives a year without a high risk of serious complications.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Confusion; Drug Overdose; Emergency Medical Services; Female; Headache; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Nausea; Norway; Prospective Studies; Seizures; Substance-Related Disorders; Tachycardia; Tremor; Vomiting

The effect of duodenal osmoreceptor stimulation on gallbladder motility was evaluated in 18 normal subjects during intraduodenal infusion of 280, 560 and 840 mosm/liters NaCl solutions. Gallbladder emptying was found to be dose-dependent between 560 and 840 mosm/liter (P less than 0.01 vs basal volume). The effect of duodenal infusion of hypertonic saline on gallbladder emptying was prevented by atropine and partially antagonized by naloxone, indicating that cholinergic and endorphinergic pathways may be involved in regulating this reflex. Since proglumide, a cholecystokinin (CCK) antagonist, did not affect gallbladder emptying induced by hypertonic saline, it seems likely that CCK is not released by increasing duodenal osmolality. A significant reduction in gallbladder volume was obtained when hyperosmolar saline was delivered into the duodenum, whereas no emptying was seen when infused into the gastric antrum or the jejunum, suggesting that osmoreceptors that activate gallbladder emptying are located only in the duodenum. Additionally, all subjects manifested central symptoms (nausea or vomiting) during duodenal infusion of hypertonic saline, suggesting that central mechanisms might be activated by a change in duodenal osmolality. Our data indicate that the osmolality of duodenal contents might regulate gallbladder motility by neural atropine- and naloxone-sensitive pathways.

Topics: Adult; Atropine; Dose-Response Relationship, Drug; Duodenum; Female; Gallbladder; Humans; Male; Middle Aged; Naloxone; Nausea; Osmolar Concentration; Proglumide; Sodium Chloride

The effects of high dose naloxone in humans have not been studied extensively. We treated 36 patients who had acute ischemic cerebral infarction with high doses of naloxone to evaluate potential efficacy and toxicity. All patients were treated with a 160-mg/m2 (4-mg/kg) loading dose followed by 80 mg/m2.h (2 mg/kg.h) x 24 h. There were no statistically significant changes in group mean arterial pressure, respiratory rate, or heart rate in response to the loading dose or infusion, although clinically significant changes did occur in four patients. Twenty-three patients had adverse reactions possibly related to naloxone, the most common of which were nausea (n = 20), bradycardia and/or hypotension (n = 3), myoclonus (n = 1), and hypertension (n = 1). Seven patients had naloxone discontinued for possible adverse reactions. All adverse reactions abated with discontinuation of naloxone and/or pharmacologic therapy when indicated. No deaths were attributable to naloxone treatment. High dose naloxone appears to be well tolerated in the majority of elderly patients with acute cerebral infarction.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cerebral Infarction; Female; Humans; Male; Middle Aged; Naloxone; Nausea

In rats, the conditioned place and taste aversions produced by 31.8 mg/kg lithium chloride were compared with those produced by 10 mg/kg gallamine in Experiment 1 and 20 mg/kg or 2.5 mg/kg naloxone in Experiments 2 and 3, respectively. Lithium produced stronger taste aversions than gallamine or the two doses of naloxone, but gallamine and naloxone each produced stronger place aversions than lithium. These findings support the distinction between two kinds of drug-induced aversive effects, having different associative properties. One effect, called sickness, is more associable with taste than with place cues; the second effect is, like pain, more associable with place than with taste.

Topics: Animals; Association; Avoidance Learning; Chlorides; Gallamine Triethiodide; Lithium; Lithium Chloride; Male; Naloxone; Nausea; Pain; Rats; Rats, Inbred Strains; Spatial Behavior; Taste

A prospective study of the effect and side-effects of epidural morphine for pain relief in 1085 patients after thoracic, abdominal, urologic, or orthopaedic surgery was performed. Morphine chloride was diluted in saline or bupivacaine and administered through an epidural catheter placed at a segmental level appropriate for the type of surgery. The initial dose was 4 or 6 mg morphine and supplementary doses were given when needed to obtain complete freedom from pain during deep breathing or nursing care. The total dose of epidural morphine from end of surgery until the next morning varied from 4 to 18 mg. 97% of hip arthroplasty patients, 91% of prostatectomy patients and thoracotomy patients, 90% of patients after major lower extremity surgery and 88% of patients after laparotomy were completely satisfied with the postoperative course. For hip arthroplasty and major extremity surgery, an initial dose of 4 mg of epidural morphine was as effective as 6 mg. After prostatectomy, laparotomy, and thoracotomy, an initial dose of 6 mg gave significantly better effect than 4 mg. Pruritus occurred in 11%, nausea or vomiting in 34%, and respiratory depression in 0.9% of the total patient population. Urinary retention occurred in 42% of patients not having urinary catheters in place. Postoperative nausea or vomiting was more frequent in women than in men (P less than 0.001). There was a higher incidence of nausea or vomiting in men experiencing pain than in men who were completely pain-free after abdominal surgery (P less than 0.001). Respiratory depression was rare and occurred as a gradually decreasing respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, Epidural; Catheterization; Depression, Chemical; Epidural Space; Humans; Morphine; Naloxone; Nausea; Pain, Postoperative; Prospective Studies; Pruritus; Respiration; Time Factors; Vomiting

Healthy male volunteers (N = 24) participated in a four-way crossover study to compare the rate and extent of absorption of naltrexone after administration of 50 mg tablets as 50, 100, and 200 mg doses and a 10 mg/ml reference syrup. A high-performance liquid chromatographic method was employed to measure naltrexone and 6-beta-naltrexol in plasma and urine. Compared to the syrup, the 50 mg tablets were absorbed more slowly but equally well. There was excellent linearity between the administered dose and the area under the plasma concentration-time profile, as well as total urinary recovery of both drug and metabolite. The mean half-lives for naltrexone and beta-naltrexol were approximately 4 and 12 hours, respectively. The fraction of drug reaching the systemic circulation was estimated to be 5% of the administered dose because of extensive first-pass metabolism. Less than 1% of the dose was excreted in the urine as naltrexone after 48 hours, while 25% was recovered as unconjugated beta-naltrexol. The renal clearance of naltrexone and beta-naltrexol was approximately 127 ml/min and 283 ml/min, respectively. The total systemic clearance for naltrexone was approximately 94 L/hr.

Topics: Administration, Oral; Adult; Dosage Forms; Dose-Response Relationship, Drug; Half-Life; Humans; Kinetics; Male; Naloxone; Naltrexone; Nausea; Tablets; Therapeutic Equivalency

In a restricted sequential trial in healthy parturient women, the pain relief from pethidine 100 mg and pethidine 100 mg combined with naloxone 0.4 mg was compared. Pethidine alone gave better relief. The incidence of minor side-effects was high with both treatments but dizziness was reduced slightly by naloxone. It was concluded that naloxone antagonized the analgesia without abolishing the side-effects of pethidine.

Topics: Anesthesia, Obstetrical; Female; Humans; Labor Stage, First; Labor, Obstetric; Meperidine; Naloxone; Nausea; Pregnancy; Time Factors; Vomiting

In 70 patients (maxillo-facial-, neurosurgical-, abdominal- and gynaecological operations) the technique of "analgetic anaesthesia" using high doses of fentanyl (0.025 mg/kg body weight) and naloxone as its antagonist (0.02 mg/kg body weight) has been employed. All patients were artificially ventilated with N2O/O2 in a 3:1 ratio. Muscle relaxation was achieved with pancuronium-bromide (0.08 mg/kg). The patients had no apparent heart or lung disease. The youngest patient was 4 years of age, the oldest 82 years of age (average age 48.9). The necessity for a reinjection of fentanyl (half the initial dose) was determined by continously monitoring heart rate. This variable appeared to be the most subtle index indicating a reduction in analgesia. Sufficient analgesia was maintained once the heart rate stayed 20% below preanaesthetic levels. At the end of the operation naloxone reversed the respiratory depression. There was no evidence indicating postoperative pain, which may have required administration of additional analgesics. If deep analgesia was maintained up to the last surgical procedures no emesis appeared in the post operative period. The incidence of emesis was higher 10% compared to the classical neuroleptanalgesia with droperidol this was often noted in cases where blood accumulated in the stomach (maxillo-facial operations) (70%). In 3% of all cases psychomotor agitation with delirium appeared right after the injection of naloxone. This lasted for about 15 minutes. We suspect that due to the sudden and powerful effect of naxolone, in replacing fentanyl from its receptor site, acute withdrawal symptoms may be precipitated.

Topics: Adolescent; Adult; Aged; Analgesia; Autonomic Nervous System; Child; Child, Preschool; Female; Fentanyl; Genital Diseases, Female; Humans; Hypertension; Hypotension; Male; Maxilla; Middle Aged; Naloxone; Nausea; Neurosurgery; Tachycardia; Vomiting

Topics: Adult; Ambulatory Care; Drug Evaluation; Female; Heroin Dependence; Humans; Legislation, Drug; Male; Middle Aged; Naloxone; Naltrexone; Nausea; New York City; Pilot Projects; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; United States

Topics: Administration, Oral; Adolescent; Adult; Attitude to Health; Constipation; Cyclazocine; Drug Evaluation; Headache; Heroin Dependence; Humans; Male; Naloxone; Nausea; Outpatient Clinics, Hospital; Patient Dropouts; Personality; Psychological Tests; Vertigo