OBJECTIVETo prepare morphine-loaded chitosan microspheres by emulsion ionic cross-linking and investigate the effect of initial morphine quantity and different cross-linking degrees on drug loading, encapsulation efficiency and in vitro drug release.

METHODSChitosan (with a relative molecular mass of 50,000 and deacetylation degree no less than 90%) at 100 mg and morphine at 20, 30, 40, or 50 mg were dissolved by 2% acetate and dripped slowly into 15 ml soy-bean oil containing 0.75 ml Span80. After full emulsification at 35 degrees C; for 1.5 h, the mixture was dripped slowly into sodium tripolyphosphate (10 mg/ml) at the mass ratio of 5:1, 7:1, or 9:1 to allow cross-linking for 2 h. The drug loading, encapsulation efficiency and in vitro drug release of the preparations were measured.

RESULTSThe drug loading in the microsphere increased while the encapsulation efficiency reduced with the increment of the initial morphine quantity. High cross-linking degree resulted in prolonged release time of the drug loaded in the preparations.

CONCLUSIONThe microspheres loaded with morphine allows sustained release of morphine.

Chitosan ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; administration & dosage ; Microspheres ; Morphine ; administration & dosage

The transdermal administration of narcotics is one of the alternative ways of providing adequate pain relief for the patients with chronic cancer pain. A Phase 4 trial was conducted to evaluate the efficacy and safety of Fentanyl-TTS in adult patients with cancer-related pain in Korea. METHODS: Patients with histologically confirmed malignancy, who have pain related to the cancer and/or therapy, pain necessitating the use of opoid analgesics, age of 18 yr or older, ability to communicate effectively with study personnel, and signed on informed consent were included. The patients were titrated with a short-acting narcotic to control their cancer pain before they are converted to a fentanyl-transdermal therapeutic system(TTS). Short acting parenteral morphine and MS contin were used as rescue medications. All patients were evaluated initially and were followed up with a pain visual analogue scale(VAS), quality of life(QOL)-VAS. Patients were asked to keep the daily record for 21 days about pain VAS, QOL-VAS, amount of rescue morphine used, and side effects. RESULTS: Twenth two patients were enrolled from January 1996 to October 1997. The dose of fentanyl-TTS required, ranged between 25 and 75 ug/hr (25 microgram/hr in 13, 50 microgram/hr in 4, and 75 microgram/hr in 2). The mean dose of morphine required before the use of the fentanyl-TTS was 135.3 mg (20-285 mg/day), but it was decreased after the use of the fentanyl-TTS. Pain VAS and QOL-VAS were in adquate level during the fentanyl- TTS treatment. Patients favored continuous use of fentanyl after the study was finished. Side effect of fentanyl-TTS was minimal. CONCLUSION: Transdermal fentanyl seems to be a convenient and effective analgesic for the control of cancer related pain in Korean. A controlled trial comparing fentanyl-TTS to morphine needs to be followed.
Administration, Cutaneous ; Adult* ; Analgesics ; Fentanyl ; Humans ; Informed Consent ; Korea ; Morphine ; Narcotics

Fentanyl, a synthetic, highly selective opioid micro-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.
Administration, Cutaneous ; Caregivers ; Fentanyl ; Heating ; Hot Temperature ; Humans ; Molecular Weight ; Morphine ; Solubility ; Steam Bath ; Transdermal Patch

BACKGROUND: Intravenous patient controlled analgesia (IV-PCA) is a most common used delivery system for intravenous administration of opioids during acute post operative pain management. The objective of this study is to compare the rate of opioid induced adverse reactions and effectiveness among two IV-PCA opioids, morphine, fentanyl, in laparoscopic cholecystectomy pain management. METHODS: Sixty patients in ASA physical status 1 and 2 scheduled for laparoscopic cholecystectomy were allocated randomly to either morphine IV-PCA used (n = 30, Group M) group or fentanyl IV-PCA used (n = 30, Group F) group. In each group, numerical rating scale (NRS) score, sedation score and incidence of side effect were checked. RESULTS: NRS score of Group F showed lower than that of Group M during PACU and 3 hrs after the recovery room (P < 0.05). There were no significant differences in sedation score among two groups. The incidences of adverse reactions were similar in the two groups, though the incidence of nausea and pruritus were higher in the Group M. CONCLUSIONS: Fentanyl IV-PCA is more advantageous than morphine IV-PCA for laparoscopic cholecystectomy in view of early pain control and adverse reaction incidences.
Administration, Intravenous ; Analgesia, Patient-Controlled ; Analgesics, Opioid ; Cholecystectomy, Laparoscopic ; Fentanyl ; Humans ; Incidence ; Morphine ; Nausea ; Pain Management ; Pruritus ; Recovery Room

Agmatine ; administration & dosage ; pharmacology ; Analgesia ; methods ; Animals ; Injections, Spinal ; Male ; Morphine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects

OBJECTIVETo evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR).

METHODSThirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured.

RESULTSThe pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05).

CONCLUSIONPreoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.

Administration, Oral ; Aged ; Analgesia, Epidural ; Anti-Inflammatory Agents ; Arthroplasty, Replacement, Knee ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Lactones ; administration & dosage ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; prevention & control ; Premedication ; Sulfones ; administration & dosage

Intraspinal narcotic anesthesia was performed in 180 open heart surgery patients. 0.1 mg/Kg of morphine or 1.5 mg/Kg of meperidine was administered as the primary anesthetic in the subarachnoid space using the barbotage technique. Of the 180 patients scheduled for open heart surgery, morphine was administered to 95 patients, meperidine to 55 and a mixture of morphine and meperidine to 30 patients. From a clinical point of view, there were no significant cardiovascular problems, however, respiratory depression seemed to be most serious after morphine administration. Mild complications such as pruritus (11.1%), voiding difficulty (10.6%), intraoperative awareness (4.4%) and spinal headache were observed, however these were mild, not major clinical problems and were acceptable. Postoperative analgesic effect and respiratory controllability were excellent.
Anesthesia, Spinal/adverse effects/*methods ; *Cardiac Surgical Procedures ; Humans ; Meperidine/*administration & dosage/adverse effects ; Morphine/*administration & dosage/adverse effects ; Respiratory Insufficiency/chemically induced

Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.
Animals ; Baclofen ; administration & dosage ; Conditioning, Classical ; GABA-B Receptor Agonists ; administration & dosage ; Locomotion ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Morphine ; Nucleus Accumbens ; drug effects ; Opioid-Related Disorders ; Reward

BACKGROUND: This study evaluated the benefits and safety of a multimodal pain control protocol, which included a periarticular injection of local anesthetics, in patients undergoing total hip arthroplasty. METHODS: Between March 2006 and March 2007, 60 patients undergoing unilateral total hip arthroplasty were randomized to undergo either a multimodal pain control protocol or a conventional pain control protocol. The following parameters were compared: the preoperative and postoperative visual analogue scales (VAS), hospital stay, operative time, postoperative rehabilitation, additional painkiller consumption, and complication rates. RESULTS: There was no difference between the groups in terms of diagnosis, age, gender, and BMI. Although both groups had similar VAS scores in the preoperative period and on the fifth postoperative day, there was a significant difference between the groups over the four-day period after surgery. There were no differences in the hospital stay, operative time, additional painkiller consumption, or complication rate between the groups. The average time for comfortable crutch ambulation was 2.8 days in the multimodal pain control protocol group and 5.3 days in the control group. CONCLUSIONS: The multimodal pain control protocol can significantly reduce the level of postoperative pain and improve patients' satisfaction, with no apparent risks, after total hip arthroplasty.
Adult ; Aged ; Amides/administration & dosage ; Analgesia/*methods ; *Arthroplasty, Replacement, Hip ; Clinical Protocols ; Female ; Humans ; Injections, Intra-Articular ; Length of Stay ; Male ; Methylprednisolone/administration & dosage ; Middle Aged ; Morphine/administration & dosage ; Narcotics/administration & dosage ; Pain/prevention & control ; Pain Measurement ; Pain, Postoperative/prevention & control

OBJECTIVETo compare the efficacy of preemptive epidural analgesia combined with postoperative epidural analgesia, postoperative epidural analgesia alone and intravenous analgesia for postoperative pain relief and their effects on plasma interleukin-6 (IL-6) concentration following radical surgery for gastric carcinoma.

METHODSSixty-six patients with gastric carcinoma scheduled for gastrectomy were randomly divided into 3 groups, namely group P (n=22), group E (n=22) and group V (n=22), to receive preemptive epidural analgesia combined with postoperative epidural analgesia, exclusive postoperative epidural analgesia, and exclusive postoperative intravenous analgesia, respectively. Hemodynamic data were recorded for all the patients during the operation, and visual analogue scale (VAS) was used to assess the pain intensity at 4, 8, 16, 24, 48 and 72 h after surgery. Plasma IL-6 concentration was determined before surgery and at 24, 48, 72 h after surgery.

RESULTSNo significant changes occurred in the hemodynamics during the preoperative periods. VAS and IL-6 were lower in group P than in group E and V, and group E had lower measurement than group V (P<0.05).

CONCLUSIONPreemptive epidural analgesia combined with postoperative epidural analgesia provides more satisfactory pain relief and more effectively prevents IL-6 increment than exclusive epidural analgesia or intravenous analgesia after gastrectomy for gastric carcinoma.

Adult ; Amides ; administration & dosage ; Analgesia, Epidural ; methods ; Analgesics ; administration & dosage ; Female ; Fentanyl ; administration & dosage ; Gastrectomy ; methods ; Humans ; Infusions, Intravenous ; Interleukin-6 ; blood ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; Stomach Neoplasms ; blood ; surgery ; Treatment Outcome