• The Korean Journal of Pain
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• 제10권2호
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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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• 제20권2호
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• pp.131-135
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• 2017

목적: 경구 oxycodone/naloxone 복합제는 아편유사제에 의해 유발되는 변비를 완화시키거나 예방하는 목적으로 사용되고 있다. Naloxone에 의해 oxycodone의 진통 효과가 상쇄되거나 금단증상이 나타난다는 보고는 거의 없었으나 저자는 실제 임상에서 몇몇 금단증상 예를 경험하였기에 이 환자들에 대한 조사 연구를 수행하였다. 방법: 2012년 1월 1일부터 2016년 12월 31일까지 경남 지역 암센터에 방문했던 진행성 암환자들로 oxycodone/naloxone extended-release tablets를 투약 받고 마약 금단증상이 나타났던 환자들의 의무기록을 후향적으로 조사하였다. 결과: 연구 기간 중 경구 oxycodone/naloxone을 처방 받은 1,641명의 암 환자 중, 총 10예(0.6%) 에서 마약 금단 증상을 겪었다. 금단증상 관련 통증 강도의 변화는 oxycodone/naloxone 투여 전 NRS 3에서 평균 NRS 6점으로 증가하였다. 금단증상 중 오한이 10예 중 7예에서 나타나 가장 많이 나타난 증상이었으며 그 외에 식은땀, 전신 쇠약감, 근육경련, 복부경련(각 5예), 불안(4예), 열, 어지럼증, 의식혼란, 하품(각 2예)의 순으로 빈번하게 관찰되었다. 결론: Oxycodone/naloxone extended-release 복합제에 의한 마약 금단증상은 흔하지는 않아도 적은 수의 환자에서라도 나타날 수 있다. 향후 이에 대한 다기관, 전향적 연구가 필요하다.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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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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• 제11권1호
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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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• 제26권1호
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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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• 제18권2호
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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.

• 대한약리학회지
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• 제17권2호
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• pp.17-22
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• 1981

Guinea-pig ileum을 naloxone을 가(加)하거나 가(加)하지 않은 전해질(電解質) 농도(濃度)가 다른 modified Krebs-Henseleit bicarbonate buffer solution에 $4^{\circ}C$에서 24시간 incubation한 다음, morphine의 수축(收縮) 억제작용(抑制作用)으 관찰(觀察)하여 다음과 같은 성적(成績)을 얻었다. 1) Incubation 자체(自體)로써 morphine의 작용(作用) 강화(强化)되었다. 2) Incubation media 내(內) 전해질(電解質) 변동(變動)은 $Na^+\;75mM$ 군(群)과 $K^+2.9mM$ 군(群)에서는 morphine의 작용(作用)이 강화(强化)되었고, $Ca^{++}\;3.6mM$ 군(群), $Mg^{++}$ free 군(群)과 $Mn^{++}\;0.2mM$ 군(群)에서는 약화(弱化)되었다. 3) Incubation media내(內) naloxone은 morphine의 작용(作用)을 강화(强化)하였다. Incubation media 내(內) naloxone을 가(加)하고 전해질(電解質)을 변동(變動)시킨 실험(實驗)에서 $Na^+\;75mM$ 군(群), $K^+2.9mM$ 군(群)과 $Ca^{++}3.6mmM$ 군(群)에서는 naloxone에 의(依)하여 morphine 작용(作用)이 약화(弱化)되었고, $Mg^{++}$ free 군(群)과 $Mn^{++}\;0.2mM$ 군(群)에서는 강화(强化)되었다. 4) Naloxone에 대(對)한 $pA_2$치(値)는 전군(全群)에서 변동(變動)이 없었다. 5) 이상(以上) 실험성적(實驗成績)은 naloxone opiate receptor에 대(對)한 작용외(作用外)에 세포막 또는 근세포수축기구(筋細胞收縮機構)에 영향(影響)을 미처 morphine의 작용(作用)에 영향(影響)을 줄 수 있음을 시사(示唆)한다.

• 대한임상독성학회지
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• 제10권1호
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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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• 제17권1호
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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.

• 한국동물학회지
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• 제33권2호
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• pp.183-190
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• 1990

본 연구는 prolactin(PRL)유전자 발현, 분비의 생리적 변화와 성주기 특정 시기의 PRL mRNA수준 및 분비에 미치는 내인성 오피오이드의 영향을 조사하였다. 최소한 두번의 연속적인 성주기를 거친 성숙한 흰쥐에서 성주기의 각 시기(10:00시)에, proestrus시기에는 10:00-20:00 시동안에는 2시간 간격으로 도살하였고, naloxone (2mg/kg b.w.)은 도살 30분전에 피하주사 하였다. PRL mRNA의 수준의 흰쥐의 PRL cDNA를 probe로 하여 RNA-blot hybridization방법에 의해서, 혈중 PRL농도 변화는 방사면역측정법에 의해 측정하였다. 뇌하수체 PRL mRNA의 수준과 혈중 PRL수준은 diestrus I, II and proestrus그리고 estrus시기의 10:00시에는 급격한 변화를 보이이 않았다. 이때 naloxone처리는 영향을 미치지 못했다. proestrus시기를 세분화하여 조사한 결과 PRL mRNA의 수준은 정오에 최고 수준에 도달하였고, 오후 6:00까지 점차적으로 감소하였다. 그후 8:00시에 다시 증가하였다. estrus동안 naloxone은 혈중의 PRL수준을 명백히 억제하였으나 PRL mRNA수준에는 영향이 없었다. proestrus시기 동안 혈중 PRL변화와 뇌하수체 PRL mRNA변화는 서로 상이하게 조절되며,PRL mRNA수준이 흰쥐 성주기 동안 변화하고 있는 사실에서 PRL 유전자 발현이 생리적으로 조절되고 있음을 시사한다.