Background: Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. Methods: To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes. Results: Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group. Conclusion: The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine.

Introduction Vincristine is a vesicant chemotherapeutic agent which may leak from the vessel at the infusion site to the perivascular tissue and cause extravasation. Extravasation, a severe complication of chemotherapeutic drugs, can result in tissue necrosis that is considered an oncological emergency. Case report We aimed to report a case of a 29-year-old woman with ALL-B cell (Acute lymphoblastic leukemia) on maintenance chemotherapy regimen including vincristine, methotrexate, prednisolone, and 6-mercaptopurine (POMP). 48 h after administering intravenous vincristine, the patient experienced burning, pain and tenderness at the injection site (left hand – cubital cavity). Management & outcome 7 days after the onset of symptoms, the patient was hospitalized with a large brown lesion at the site. She was prescribed betamethasone cream, DSMO (Dimethyl sulfoxide) solution, and oral levofloxacin on his second day after admission. The lesion was completely improved 10 days after initiation of therapy and there were no serious problems. Discussion Due to the ineffectiveness of antidote therapy for the management of delayed extravasation of vincristine and beneficial effect of our clinical approach, it could consider for the management of similar cases with delayed extravasation following vincristine administration.