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European Journal of Clinical... Jun 2015The aim of the study was to determine the extent of inter-individual variation in clearance of intravenous morphine in children and to establish which factors are... (Review)
Review
OBJECTIVES
The aim of the study was to determine the extent of inter-individual variation in clearance of intravenous morphine in children and to establish which factors are responsible for this variation.
METHODS
A systematic literature review was performed to identify papers describing the clearance of morphine in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL, and Cochrane library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.
RESULTS
Twenty-eight studies were identified. After quality assessment, 20 studies were included. Only 10 studies gave clearance values for individual patients. The majority of the studies were in critically ill patients. Inter-individual variability of morphine clearance was observed in all age groups, but greatest in critically ill neonates (both preterm and term) and infants. In critically ill patients, the CV was 16-97% in preterm neonates, 24-87% in term neonates, 35 and 134% in infants, 39 and 55% in children, and 74% in adolescents. The CV was 37 and 44% respectively in non-critically ill neonates and infants. The mean clearance was higher in children (32 and 52 ml min(-1) kg(-1)) than in neonates (2 to 16 ml min(-1) kg(-1)).
CONCLUSIONS
Large inter-individual variation was seen in morphine clearance values in critically ill neonates and infants.
Topics: Child; Critical Illness; Humans; Individuality; Morphine
PubMed: 25845657
DOI: 10.1007/s00228-015-1843-x -
The American Journal of the Medical... Sep 2015
Topics: Analgesics, Opioid; Gastroparesis; Humans; Male; Middle Aged; Morphine; Tomography, X-Ray Computed
PubMed: 25798832
DOI: 10.1097/MAJ.0000000000000450 -
Neuropharmacology Feb 2023Morphine tolerance (MT) caused by long-term use of morphine is a major medical problem. The underlying molecular mechanisms of morphine tolerance remain unclear. Here,...
Morphine tolerance (MT) caused by long-term use of morphine is a major medical problem. The underlying molecular mechanisms of morphine tolerance remain unclear. Here, we establish the morphine tolerance model in mice and verify whether a novel circRNA, circRalgapa1 is involved in morphine tolerance and its specific molecular mechanism. We show that the expression of circRalgapa1 in the spinal cord is significantly down-expressed in the spinal cord of morphine-tolerant mice. CircRalgapa1 is mainly located in the neuronal cytoplasm and co-localizes with miR-873a-5p. Mechanically, circRalgapa1 acts as competing endogenous RNAs (ceRNAs) to regulate the inhibitory of miR-873a-5p on A20 (also known as tumor necrosis factor α-induced protein 3, TNFAIP3). Functionally, overexpression of circRalgapa1 by intrathecal injection of adeno-associated virus (AAV- circRalgapa1) attenuated the formation of morphine tolerance and partially reversed the development of morphine tolerance. Moreover, overexpression of miR-873a-5p blocked the effect of AAV-circRalgapa1 on alleviating morphine tolerance in mice. In conclusion, chronic morphine administration-mediated down-regulation of circRalgapa1 in the spinal cord contributes to morphine tolerance via miR-873a-5p/A20 axis in mice. Overexpression of circRalgapa1 may be a promising RNA-based therapy for morphine tolerance.
Topics: Animals; Mice; Cytoplasm; Down-Regulation; MicroRNAs; Morphine; Spinal Cord; RNA, Circular; Drug Tolerance
PubMed: 36455645
DOI: 10.1016/j.neuropharm.2022.109353 -
Journal of Veterinary Pharmacology and... Jul 2023The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been...
The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four-way balanced crossover design, with a 2-week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (C : 11.6-37.8 ng/mL (0.6 mg/kg); 15.8-42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti-nociceptive effects of morphine following oral administration.
Topics: Animals; Administration, Oral; Analgesics, Opioid; Biological Availability; Horses; Morphine; Morphine Derivatives; Cross-Over Studies
PubMed: 36883679
DOI: 10.1111/jvp.13122 -
Journal of Palliative Care Apr 2022Previous research unambiguously establishes the importance of knowledge and education about opioids and pain management in medical care. This article aimed at...
Previous research unambiguously establishes the importance of knowledge and education about opioids and pain management in medical care. This article aimed at describing the perception of the general public on the uses and the risks of morphine in palliative care in an Ecuadorian sample, where training and access to those services is limited. We used an online recruited sample of 257 participants for this cross-sectional descriptive study. Participants responded to an online self-report survey regarding morphine's effects and its relationship with addiction and death in a palliative care context. Analyses indicate that there is a lack of understanding about the effectiveness of morphine and that, overall, participants did not associate morphine with death and dying. Results also show that people in health-related occupations did not differ from the general public in beliefs about the addiction and the effectiveness of morphine. However, occupation and education effects were noted for several other items, as well as whether the participants had direct experiences with palliative care as either a patient or a caregiver. There is still misinformation about opioids such as morphine in the general public and health professionals in Ecuador. Although personal experiences with pain control and palliative care are linked to better knowledge about opioids, education is still necessary to overcome the myths around them. Future research could address the found misconceptions to increase health literacy through education policies and interventions.
Topics: Analgesics, Opioid; Cross-Sectional Studies; Ecuador; Humans; Morphine; Palliative Care
PubMed: 34128421
DOI: 10.1177/08258597211026398 -
Brain and Nerve = Shinkei Kenkyu No... Dec 2023Christie's Sad Cypress features an impressive trick with morphine and apomorphine. I read the book as if I were this killer, and also thought about the effects of...
Christie's Sad Cypress features an impressive trick with morphine and apomorphine. I read the book as if I were this killer, and also thought about the effects of morphine and apomorphine.
Topics: Humans; Morphine; Apomorphine; Cupressus
PubMed: 38097220
DOI: 10.11477/mf.1416202530 -
Central Nervous System Agents in... 2022Chronic morphine stimulates prolonged stimulation of opioid receptors, especially μ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the sudden...
BACKGROUND
Chronic morphine stimulates prolonged stimulation of opioid receptors, especially μ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the sudden termination of the use of morphine after chronic intake causes the withdrawal syndrome.
OBJECTIVES
Hence, this study was designed to find an alternative treatment for morphine withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum) for the treatment of morphine-exposed neuroblastoma cell lines.
METHODS
SK-N-SH, a commercialised neuroblastoma cell line, was used in two separate study designs; the antagonistic and pre-treatment of morphine. The antagonistic treatment was conducted through concurrent exposure of the cells to morphine and E. cuneatum or morphine and methadone for 24 hrs. The pre-treatment design was carried out by exposing the cells to morphine for 24 hrs, followed by 24 hrs exposure to E. cuneatum or methadone. The cytosolic fraction was collected and assessed for proteins expression involved in cellular adaptation, including mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signalregulated kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA) and protein kinases C (PKC).
RESULTS
The antagonistic treatment showed the normal level of MEK 1/2, ERK 2, PKA and PKC by the combination treatment of morphine and E. cuneatum, comparable to the combination of morphine and methadone. Neuroblastoma cells exposed to morphine pre-treatment expressed a high level of MEK 1/2, ERK 2, PKA and PKC, while the treatments with E. cuneatum and methadone normalised the expression of the cellular adaptation proteins.
CONCLUSION
E. cuneatum exerted anti-addiction properties by lowering the levels of cellular adaptation proteins it's effects is comparable to that of methadone (an established anti-addiction drug).
Topics: Analgesics, Opioid; Humans; Methadone; Morphine; Neuroblastoma
PubMed: 35578883
DOI: 10.2174/1871524922666220516151121 -
Blocking Palmitoylation of Apelin Receptor Alleviates Morphine Tolerance in Neuropathic Cancer Pain.International Journal of Biological... 2024Neuropathic cancer pain (NCP) is an important symptom in patients with cancer. However, significant analgesic tolerance and other side effects critically hamper the...
Neuropathic cancer pain (NCP) is an important symptom in patients with cancer. However, significant analgesic tolerance and other side effects critically hamper the administration of morphine. Protein palmitoylation mediated by the DHHC family may be involved in the glial activation and inflammatory responses underlying organ failure. In this study, we investigated the key role of protein palmitoylation in cancer pain and sought to target palmitoylation to suppress morphine tolerance. We found that long-term use of morphine led to the accumulation of the morphine metabolite, morphine-3-glucuronide, and activated ERK1/2 and microglia to release inflammatory factors through the apelin receptor APLNR. Palmitoyltransferase ZDHHC9 was upregulated in NCP, and APLNR was palmitylated to protect it from lysosomal degradation and to maintain its stability. We also designed competitive inhibitors of APLNR palmitoylation to inhibit the development of NCP, release of inflammatory factors, and attenuation of morphine tolerance. Therefore, targeting APLNR palmitoylation in combination with morphine is a potent method for cancer pain treatment. Our data provide a basis for the future clinical use of related drugs combined with morphine for the treatment of cancer-related pain.
Topics: Humans; Morphine; Apelin Receptors; Cancer Pain; Lipoylation; Neuralgia; Neoplasms
PubMed: 38164190
DOI: 10.7150/ijbs.86888 -
International Journal of Developmental... May 2023Maternal morphine exposure reduces motivation for basic cognitive tasks, followed by executive function deficits in attention and accuracy. It also induces...
Maternal morphine exposure reduces motivation for basic cognitive tasks, followed by executive function deficits in attention and accuracy. It also induces depression-like behaviors and has negative consequences for learning and memory in offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal separation (MS) can originate behavioral and neuropsychiatric abnormalities later in life. It seems that adolescents are more susceptible to the effects of early-life stress; Therefore, this study aimed to evaluate the effects of chronic morphine consumption (21 days before and after mating and gestation) and MS (180 min/day from postnatal day [PND] 1-21) on the cognitive and behavioral performance of male offspring in mid-adolescence. Six groups, including control, MS, V (vehicle), morphine, V+MS, and morphine+MS, were tested for open field (OF), novel object recognition (NOR), and the Morris water maze (MWM). The results of the OF test showed that MS increased locomotor activity and movement velocity. Inner and outer zone durations did not differ among groups. The body stretching of the morphine+MS rats was significantly more than the MS rats. Moreover, the MS and morphine+MS groups showed significantly less sniffing behavior in the OF test. The MS group showed deficits in spatial learning in the MWM test, but recognition memory in the NOR and spatial memory in the MWM tests were not significantly different among groups. We concluded that MS could induce impairments in spatial learning and locomotor activity that could be worsened by maternal morphine exposure in adolescent male rats.
Topics: Rats; Animals; Male; Morphine; Rats, Wistar; Maze Learning; Maternal Deprivation; Cognition; Locomotion; Mammals
PubMed: 36794284
DOI: 10.1002/jdn.10251 -
Journal of Neuroimmune Pharmacology :... Jun 2022HIV-associated neurocognitive disorders (HAND) are a collective name for neurological disorders associated with HIV-1 infection. The incidence and severity of HAND are...
HIV-associated neurocognitive disorders (HAND) are a collective name for neurological disorders associated with HIV-1 infection. The incidence and severity of HAND are increased by concomitant opioid use disorder, such as heroin and morphine abuse. Our previous study showed that the HIV-1 envelope protein gp120 and morphine synergistically induce apoptosis in rat hippocampal neurons. However, the underlying mechanism remains unclear. We hypothesized that morphine and gp120 activated the neuronal apoptosis signaling pathway via their typical membrane receptors. If they shared key signaling molecules, their induction of neuronal apoptosis could be inhibited by blocking these targets. We found that morphine and gp120V3 loop synergistically induced hippocampal neuron apoptosis, mediated by activating the extracellular signal-regulated kinase (ERK) pathway, increasing the intracellular Ca2 + concentration and expression of caspase-, and reducing the mitochondrial membrane potential. The ERK inhibitor PD98509 and the phosphatidylinositol 3-kinase activator IGF-1 blocked this effect. These results indicate that ERK plays a crucial role in the apoptosis of hippocampal neurons in HAND.
Topics: Rats; Animals; HIV; Morphine; Neurons; HIV Infections; Apoptosis
PubMed: 33791922
DOI: 10.1007/s11481-021-09989-0