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Neuromodulation : Journal of the... Aug 2023Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery...
BACKGROUND
Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use.
MATERIALS AND METHODS
The stability study method was conceived according to the International Council for Harmonization guidelines. For polypropylene syringes, four different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over seven days. Two storage temperatures were tested (5 ± 3 °C and 25 ± 2 °C). For implantable pumps, two different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over 28 days and stored at 37 °C.
RESULTS
For the morphine-clonidine mixtures in polypropylene syringes, all mixtures remained stable for five days in both storage conditions (5 ± 3 °C and 25 ± 2 °C) because of relative concentrations systematically positioned between 90% and 110% (95% CIs of the mean of three samples). The two mixtures in implantable pumps remained stable for 28 days. For the sufentanil-clonidine mixtures in polypropylene syringes, cold conservation kept all the preparations stable for seven days, whereas a quick degradation was observed after only two days for ambient storage conditions. This result is similar to that with an implantable pump, in which the concentration is <90% on day 7 for low concentration mixtures. No visual modification, no significant pH modification, and no changes in turbidity assays were observed in either study.
CONCLUSION
This study shows the stability of the morphine-clonidine mixtures in syringes stored at 5 °C for five days and in implantable pumps stored at 37 °C for 28 days. For the sufentanil-clonidine mixtures, the results show stability in syringes for seven days at 5 °C. Pump results show stability of seven days for low concentrations and 28 days for high concentrations.
Topics: Humans; Morphine; Sufentanil; Clonidine; Polypropylenes; Pain
PubMed: 36038481
DOI: 10.1016/j.neurom.2022.07.008 -
ACS Chemical Neuroscience Oct 2018As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex... (Review)
Review
As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex phenanthrene alkaloid produced by Papaver somniferum, morphine has fascinated chemists seeking to disentangle pharmacologically beneficial analgesic effects from addiction, tolerance, and dependence liabilities. In this review, we will detail the history of morphine, from the first extraction and isolation by Sertürner in 1804 to the illicit use of morphine and proliferation of opioid use and abuse disorders currently ravaging the United States. Morphine is a molecule of great cultural relevance, as the agent that single-handedly transformed our understanding of pharmacognosy, receptor dynamics, and substance abuse and dependence disorders.
Topics: Analgesics, Opioid; Drug Tolerance; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Morphine; Opioid-Related Disorders; Pain; Papaver; Receptors, Opioid; United States
PubMed: 29757600
DOI: 10.1021/acschemneuro.8b00150 -
American Journal of Health-system... Nov 2016A case of severe bilateral sensorineural hearing loss associated with oral morphine is reported.
PURPOSE
A case of severe bilateral sensorineural hearing loss associated with oral morphine is reported.
SUMMARY
A 52-year-old Spanish man was admitted to the intensive care unit with a Glasgow Coma Scale score of 3, a fever, and sudden hearing loss with tinnitus in both ears. His medical history included type 2 diabetes mellitus, depression, sleep disorder, and hypertension. The patient also had pyelonephritis in 2011 and pulmonary embolism in 2014, requiring the placement of an inferior vena cava filter and chronic anticoagulation. His hearing loss appeared after the initiation of oral morphine, specifically on the eighth day of treatment, with increasing dosages of up to 120 mg daily. We did not find any other possible causes of the hearing loss. Ototoxicity is an adverse reaction of ibuprofen and acetaminophen, but the patient received only three doses of ibuprofen 600 mg and did not require acetaminophen. The patient's other medications did not have ototoxicity as an adverse reaction, and the patient confirmed not to have received any salicylate product. Brain magnetic resonance imaging discarded other possible causes of hearing loss. Our patient's hearing loss did not resolve after opioid discontinuation, and the use of hearing aids was necessary. According to the Naranjo et al. adverse drug reaction probability scale, this event would be classified as "probable."
CONCLUSION
A 52-year-old man developed tinnitus and hearing loss after receiving high doses of oral morphine sulfate. His hearing loss did not fully resolve after the discontinuation of morphine, and he required the use of hearing aids.
Topics: Analgesics, Opioid; Hearing Loss, Sensorineural; Humans; Male; Middle Aged; Morphine
PubMed: 27821396
DOI: 10.2146/ajhp151012 -
MMW Fortschritte Der Medizin May 2021
Review
Topics: Delayed-Action Preparations; Dyspnea; Health Status; Humans; Morphine; Pulmonary Disease, Chronic Obstructive
PubMed: 34033036
DOI: 10.1007/s15006-021-9986-4 -
Drug Development Research Sep 2021Morphine-6-O-sulfate (M6S), a polar, zwitterionic sulfate ester of morphine, is a powerful and safe analgesic in several rat models of pain. A sensitive liquid...
Morphine-6-O-sulfate (M6S), a polar, zwitterionic sulfate ester of morphine, is a powerful and safe analgesic in several rat models of pain. A sensitive liquid chromatography-tandem mass spectrometry bioanalytical method was developed and validated for the simultaneous determination of M6S and morphine (MOR) in rat plasma and brain after M6S administration. Morphine-d was used as internal standard. Multiple reaction monitoring was used for detection and quantitation of M6S, MOR, and morphine-d in the turbo ion spray positive mode. The chromatographic separation was carried out on an Alltech Altima C18 column. The analytical method was validated for linearity, precision, accuracy, specificity, and stability over a concentration range of 3-8000 ng/ml in rat plasma and 10-10,000 ng/ml in brain samples for both M6S and MOR. The validated method was applied to determine the PK profile of M6S in plasma after i.v., i.p., and oral dosing in male Sprague-Dawley rats. Rats were administered M6S by i.p. administration (5.6 and 10.0 mg/kg) or orally (10 and 30 mg/kg) and bioavailability compared to an i.v. injection (1 mg/kg) of M6S. The in vivo results indicate that M6S is not a prodrug of morphine, since M6S is not biotransformed into MOR in plasma after either i.p. or oral administration, and MOR was not detected in brain. The bioavailability of M6S was >93% and about 5% after i.p. and oral dosing, respectively. The low oral bioavailability of M6S may be due to poor permeation of the intestinal epithelial membrane. After i.p.-administration, M6S appears to reach brain tissues in low, but significant, concentrations.
Topics: Animals; Brain; Male; Morphine; Morphine Derivatives; Rats; Rats, Sprague-Dawley
PubMed: 33427316
DOI: 10.1002/ddr.21785 -
Journal of Anesthesia History Apr 2017
Topics: History, 19th Century; Humans; Morphine
PubMed: 28641830
DOI: 10.1016/j.janh.2017.03.001 -
Science Advances Jun 2023The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain...
The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTA) to the IPAC lateral region GABAergic neurons (IPACL) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcSh) to the IPAC medial region GABAergic neurons (IPACM) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAIPACL and NAcShIPACM were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.
Topics: Morphine; Ventral Tegmental Area; Reward; GABAergic Neurons; gamma-Aminobutyric Acid
PubMed: 37352353
DOI: 10.1126/sciadv.adg5849 -
Immunopharmacology and Immunotoxicology Dec 2022Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even...
BACKGROUND
Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis.
METHOD
DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine.
RESULT
Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, μ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice.
CONCLUSION
Our findings suggest that fentanyl exacerbates murine colitis Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.
Topics: Mice; Animals; Trinitrobenzenesulfonic Acid; Fentanyl; Mice, Inbred C57BL; Morphine
PubMed: 35848944
DOI: 10.1080/08923973.2022.2102993 -
Fundamental & Clinical Pharmacology Feb 2021Morphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other... (Review)
Review
Morphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other side effects including dependence, addiction, respiratory depression, and constipation, which limit its clinical usage. Therefore, identifying the new analgesics with fewer side effects which could increase the effect of morphine and reduce its side effects is crucial. Melatonin, a multifunctional molecule produced in the body, is known to play an important role in pain regulation. The strong anti-inflammatory effect of melatonin is suggested to be involved in the attenuation of the pain associated with inflammation. Melatonin also increases the anti-nociceptive actions of opioids, such as morphine, and reverses their tolerance through regulating several cellular signaling pathways. In this review, published articles evaluating the effect of the co-consumption of melatonin and morphine in different conditions were investigated. Our results show that melatonin has pain-killing properties when administered alone or in combination with other anti-nociceptive drugs. Melatonin decreases morphine consumption in different pathologies. Furthermore, attenuation of morphine intake can be accompanied by reduction of morphine-associated side-effects, including physical dependence, morphine tolerance, and morphine-related hyperalgesia. Therefore, it is reasonable to believe that the combination of melatonin with morphine could reduce morphine-induced tolerance and hyperalgesia, which may result from anti-inflammatory and antioxidant properties of melatonin. Overall, we underscore that, to further ameliorate patients' life quality and control their pain in various pathological conditions, melatonin deserves to be used with morphine by anesthesiologists in clinical practice.
Topics: Analgesics; Arachidonate 5-Lipoxygenase; Calcium; Drug Tolerance; Humans; Hyperalgesia; Melatonin; Morphine
PubMed: 32415694
DOI: 10.1111/fcp.12566 -
Psychopharmacology Aug 2022Alongside a pathological, excessive, motivation for substances of abuse, substance use disorder (SUD) patients often show a dramatic loss of interest for naturally...
RATIONALE
Alongside a pathological, excessive, motivation for substances of abuse, substance use disorder (SUD) patients often show a dramatic loss of interest for naturally rewarding activities, such as positive peer social interaction and food intake. Yet, pre-clinical evidence of the latter SUD features remains scarce and inconsistent.
OBJECTIVES
In the current study, we investigated the effect of non-rewarding and rewarding doses of morphine upon social behaviour, motivation for and intake of palatable food, in male and female C57BL/6J mice.
METHODS
First, the rewarding effects of two relatively low morphine doses (1.25 and 2.5 mg/kg) were assessed using a newly established single substance administration/conditioning trial conditioned place preference (CPP) paradigm. Then, morphine (1.25 and 2.5 mg/kg) effects upon social behaviour, motivation for and intake of palatable food were examined by the three-chamber (3-CH), an operant behaviour and a palatable food preference test, respectively.
RESULTS
Morphine (2.5 mg/kg) induced CPP in both male and female mice, whereas morphine (1.25 mg/kg) induced CPP only in female mice. Both morphine doses (1.25 and 2.5 mg/kg) reduced sociability, motivation for and intake of palatable food in male and female mice, independently of cognitive function or locomotor activity.
CONCLUSIONS
Female mice were more sensitive than male mice to the rewarding effects of morphine. Moreover, both a non-rewarding and a rewarding dose of morphine impaired the interest for naturally rewarding activities, indicating that brain reward systems might be more sensitive to the deleterious than to the rewarding effects of substances of abuse.
Topics: Animals; Brain; Conditioning, Operant; Dose-Response Relationship, Drug; Female; Male; Mice; Mice, Inbred C57BL; Morphine; Motivation; Reward
PubMed: 35396673
DOI: 10.1007/s00213-022-06131-7