• The Korean Journal of Pain
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• v.10 no.2
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• pp.208-213
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• 1997

Background: Pruritus is the most frequent undesirable symptom associated with epidural morphine. It is unpleasant and often difficult to treat. Naloxone is presently the drug of first choice for treating this symptom. Naloxone however decrease the pain threshold in some cases. Recently it was reported subhypnotic doses of propofol were efficient in relieving epidural-morphine-induced pruritus(EMIP). In a prospective. randomized, double-blinded clinical trial, we compared the efficacy of propofol and naloxone for treatment of EMIP. Methods: Forty patients with EMIP were allocated to receive either 20 mg propofol, or 1.5 ${\mu}g/kg$ naloxone intravenously. Pruritus and level of postoperative pain were assessed after 5 min, using pruritus rating scale and visual analogue scale. Results: The overall success rate in treating pruritus was similar in both groups (propofol 70% vs naloxone 65%). Twenty-five percent of the patients in the naloxone group had an increase in the level of postoperative pain versus none in the propofol group(P=0.018). Conclusions: These results suggest propofol and naloxone are equally effective in treating EMIP. However, the level of postoperative pain is significantly reduced when treated with propofol.

• Journal of Hospice and Palliative Care
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• v.20 no.2
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• pp.131-135
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• 2017

Purpose: Oral naloxone is combined with oxycodone to alleviate or prevent opioid-induced constipation in cancer pain patients. However, there is still concern that oral naloxone may precipitate opioid withdrawal symptoms in patients on opioids. We retrospectively investigated clinical characteristics of cancer patients who experienced opioid withdrawal symptoms. Methods: We reviewed medical records of all patients who were prescribed with oral oxycodone/naloxone at a tertiary cancer center from January 1, 2012 through December 31, 2016. Eligible patients were screened based on demographics, opioid and naloxone dosages, clinical manifestation and pain intensity. Results: Among a total of 1,641 patients, 10 patients were selected. Seven patients were male, and the average age was 68.1 years. The median dose of naloxone that induced withdrawal symptoms was 20 mg. Most common withdrawal symptom was shivering (seven patients) followed by cold sweating (five), and muscle twitching (five). Other symptoms included restlessness, fever, dizziness, and yawning. Pain was exacerbated from the median intensity of numeric rating scale (NRS) 3 to NRS 6. Conclusion: Opioid withdrawal symptoms may occur when switching to oral oxycodone/naloxone for cancer patients who have been treated with other strong opioids. A prospective, multicenter study on this issue should be conducted in future.

• Journal of Pharmaceutical Investigation
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• v.27 no.3
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• pp.225-231
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• 1997

For the effective administration of naloxone, we attempted to investigate the naloxone sustained-release implants. Using the biodegradable polymer, poly[(diethyl glutamate)-co-(ethyl glycinate)phosphazenes](PGGP), the implantable devices containing naloxone hydrochloride(NLX HCl) and naloxone base(NLX) were prepared. The release rates of NLX and NLX HCl were compared. Influences of NLX contents on release rates were examined. For pharmacokinetic studies, NLX and NLX HCl loaded devices were implanted subcutaneously in rabbits and then the plasma concentrations of NLX were determined by HPLC(ECD). NLX-containing devices were implanted with various doses and pharmacokinetic parameters according to dose were calculated. The relative bioavailabilities were evaluated and compared. Incorporation of NLX in the polymer leaded to a slow release. There were no differences of release rates based on drug contents. In pharmacokinetic parameters determined in 216 hours, NLX loaded devices resulted in enhanced bioavailability with the higher AUC (p<0.01) than NLX HCl loaded devices and MRT was significantly (p<0.05) increased. This result demonstrates that NLX is more suitable for sustained release devices than NLX HCl. Therefore it is anticipated that the effective concentrations of naloxone could be maintained for longer periods and bioavailabilities could be improved by naloxone sustained-release implants, with varying drug base/hydrochloride.

• The Korean Journal of Pain
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• v.11 no.1
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• pp.47-53
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• 1998

Background: Epidural coadministration of opioids and local anesthetics has provided excellent analgesia during postoperative period. However, it is usually associated with the occurance of many side effects which were induced by epidural morphine. Low dose of intravenous naloxone has been known to reduce morphine-induced side effects without reversing analgesia, but the effect of epidural naloxone has not been defined in human study. Therefore we evaluated side effects and analgesia when naloxone was administered via epidural route. Methods: Eighty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of four study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly at 1 hr before the end of surgery and continuous epidural infusion was started by Two-day Infusor containing morphine 4 mg in 0.125% bupivacaine 100 ml with either none of naloxone(Group 1, n=20), 2 ug/kg/day of naloxone(Group 2, n=20), 3 ug/kg/day of naloxone(Group 3, n=20) or 4 ug/kg/day of naloxone(Group 4, n=20). Study endpoints included visual analog scales(VAS) for pain, severity of nausea, itching, somnolence and respiratory depression. They were assessed at 2, 4, 8, 16, 32, and 48 hr postoperatively. Results: VAS for pain showed significant difference in Group 4 compared with Group 1 at all of the evaluation time. Itching score decreased significantly in Group 3 and 4 after 8 hr postoperatively and nausea score decreased significantly in Group 3 after 4 hr postoperatively. Alertness score decreased significantly in Group 3 and 4 especially in early postoperative period. Conclusion: This study suggests that epidural naloxone reduce morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect of epidural morphine.

• Journal of Hospice and Palliative Care
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• v.26 no.1
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• pp.18-21
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• 2023

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.124-132
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• 2005

Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 ($5{\mu}g$), 10 : 1 ($10{\mu}g$), and 1 : 1 ($100{\mu}g$) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2-3, 5-6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P < 0.05). In the three naloxone groups, the numbers of flinches were transiently reduced following the naloxone injection in the low- and medium-dose groups compared to those of the morphine group (P < 0.05). The duration of the reduced flinches was longer in the medium-dose group (P < 0.05). The high-dose group revealed immediate increases in flinches immediately after the naloxone injection compared to those of the morphine, low- and medium-dose groups (P < 0.05 for each). The spinal c-fos expression showed no significant patterns between the experimental groups. Conclusions: Our data suggest that relatively low-dose naloxone (1/20 to 1/10 dose-ratio of morphine) transiently potentiates morphine analgesia; whereas, high-dose (equal dose-ratio of morphine) reverses the analgesia, and the spinal c-fos expression does not always correlate with pain behavior in the rat formalin test.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.17-22
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• 1981

In the electrically stimulated guinea-pig ileum, which was incubated in the modified Krebs-Henseleit bicarbonate buffer solution containing various concentrations of electrolytes at $4^{\circ}C$ for 24 hours, the effect of naloxone on the inhibitory action of morphine was investigated. Incubation potentiated the inhibitory action of morphine. In the incubated preperation, the inhibitory action of morphine was potentiated in the $Na^+\;75mM$, and $K^+\;2.9mM$ groups, while that action of morphine was reduced in the $Ca^{++}\;3.6mM,\;Mg^{++}$ free and $Mn{++}\;0.2mM$ groups. Naloxone in incubation media potentiated in the inhibitory action of morphine. In the preparations which were incubated in various concentrations of electrolytes plus naloxone, the action of morphine was reduced in $Na^+\;75mM,\;K^+\;2.9mM$, and $Ca^{++}\;3.6mM$ groups, while that action of morphine was potentiated in $Mg^{++}$free and $Mn{++}\;0.2mM$ groups. Naloxone antagonised those actions of morphine. However, $pA_2$ values for naloxone (index for affinity for antagonist) was not changed. Thus changes in the inhitory action of morphine caused by incubation are probably not the result of changes in the affinity of receptor, but due to the alterations in the events which precede or follow the receptor binding by incubations.

• Journal of The Korean Society of Clinical Toxicology
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• v.10 no.1
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• pp.33-36
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• 2012

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.

• Journal of Ginseng Research
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• v.17 no.1
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• pp.22-28
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• 1993

This study was undertaken to determine the effects of ginseng total saponin (GTS) on stress- induced analgesia (SIA) in mice. intermittent foot shock (FS)-SIA was antagonized not by on but by naloxone in the tail flick FS-SIA which was not antagonized by naloxone in the T.F. test. On the other hand, GTS did not antagonize the continuous FS-SIA naloxone antagonized in the T.P. test. Also GTS antagonized psychological (PSIF)-SIA which was not antagonized by naloxone in the T.F. test. However, GTS did not antagonize the PSY-SIA which naloxone antagonized in the T.P. test. Forced swimming (FSIP)-SIA was not affected by both GTS and naloxone. These results suggest that the antapeonisms of intermittent FS-SIA in the T.F. test, continuous FS-SIA and PSY-SIA by GTS are mediated by non-opioid mechanisms but the antagonism of intermittent FS-SIA in the T.P. test by GTS is mediated by opioid mechanism.

• The Korean Journal of Zoology
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• v.33 no.2
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• pp.183-190
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• 1990

The present study exarnines the physiological alteradons in prolactin (PRL) messenger ribonucleic acid (mRNA) and serum PRL levels during the rat estrous cycle and the effed of naloxone, an endogenous oploid peptide receptor antagonist, on PRL gene expression during the rat estrous cycle. Adult female rats exhibiting at least two consecutive 4-day estrous cycles were used in this study. A single injection of naloxone (2mg/kg b.w.) or saline was given sc 30 mm prior to decapitation. Animals were sacrificed at 10:00 h of each stage of the estrous cycle, and at 2-h intervals from 10:00 h to 20:00 h during the proestrus. PRL mRNA and serum PRL levels were determined by a RNA-blot hybridization with the rat PRL cDNA probe and by a PRL radjoimmunoassay, respectively. PRL mRNA and serum PRL levels were not dramatically altered in the morning of each stage of diestrus I, II and proestrus, and naloxone failed to modify the two parameters. During estrus naloxone clearly suppressed serum PRL levels, but it was unable to modify PRL mRNA levels. A more detailed examination of the proestrus stage revealed that PRL mRNA and serum PRL levels were fluctuated as a function of time: PRL mRNA levels reached a maximum level at 12:00 h and gradually decreased until 18:00 h. PRL mRNA levels then rose at 20:00 h. No difference of PRL mRNA levels between the control and naloxone-treated groups was observed. Changes in serum PRL levek during proestrus were conversely related to changes in PRL mRNA: serum PRL levels were low from 10:00 h to 14:00 h, then increased and reached a maximum level at 16:00-18:00 h. Following then, serum PRL levels were decreased. Naloxone was effective in suppressing the charaderistic afternoon surge of PRL from 16:00 h to 20:00 h. These data clearly showed that alterations in PRL mRNA levels were conversely correlated with changes mn serum PRL levels on proestrus, indicating a differential regulation of PRL gene expression and secretion.