Browsing by Subject "morphine"

The nucleus accumbens (NAc) is located in the ventral striatum and plays a critical role in drug addiction. NAc receives dopaminergic projections from ventral tegmental area (VTA) which is activated after administration of various abused drugs. Activation of VTA increases the release of dopamine in NAc. Increased dopamine levels induce the release of acetylcholine from striatal cholinergic interneurons. These cholinergic interneurons have been related to the development of addiction and other emotion-related disorders such as depression. Previous studies have shown that a lesion of cholinergic interneurons led to an increase in morphine-induced conditioned place preference in mice. Moreover, an activation of cholinergic interneurons by designer receptors (DREADD) has reduced food consumption motivated by food restriction. The purpose of this study was to investigate whether accumbal cholinergic interneurons mediate alcohol- and morphine-induced conditioned place preference and locomotor activity. The activation of cholinergic interneurons was controlled using DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology. DREADDs are G protein-coupled receptors. Cellular function and activation can be modulated by these receptors. DREADDs are activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). Fluorescent protein, mCherry, is attached to DREADDs so that the expression of receptors in brain tissue can be observed. Cre-spesific adeno-associated viruses (AAV) with DREADD gene were injected bilaterally to the nucleus accumbens of ChATcre mice in stereotactic surgery. The effects of alcohol and morphine were tested with conditioned place preference procedure. Mice were divided to three groups after DREADDs: activating receptor Gq (n = 10), inhibiting receptor Gi (n = 9) and control mC (n = 9). There were both male and female mice in every group. Alcohol did not induce conditioned place preference in any group. The locomotor activity of mice significantly increased after alcohol injection compared to saline injection. However, cholinergic interneurons had no effect on the increased locomotor activity. Morphine-induced conditioned place preference was expressed in every group but there were no significant differences between DREADDs and control group when the first 15 minutes and the whole 30 minutes of the place preference test was analysed. Though, Gq-receptor seemed to decrease the place preference compared to control group when the place preference test was observed in five minute intervals. Morphine also significantly increased the locomotor activity of mice, but there were no differences between the groups. Sex had no influence on the place preference, but female mice were more active than male mice during the alcohol conditioning and the alcohol place preference test. The locomotor activity of female mice also increased more than the activity of male mice after morphine injection. The effect of accumbal cholinergic interneurons on alcohol-induced conditioned place preference remained unclear. Activation of cholinergic interneurons suppressed morphine-induced conditioned place preference compared to control group but not enough so that the effect could be seen during the whole place preference test. The mice were same in the morphine test as in the alcohol test so the mice were conditioned to alcohol before morphine and therefore the results of morphine-induced conditioned place preference are not reliable.

The medication process in palliative care is prone to medication errors and their significant consequences.The complex nature of palliative care medication includes frequent use of parenteral drugs and drug mixtures. Many of the medications used parenterally are considered high-alert medications which carry a significant risk of harm if used in error. By investing in medication safety initiatives, quality of palliative care can be improved, and costs reduced. The aim of this study was to identify the most common compositions of parenteral morphine and oxycodone mixtures administered in patient units providing special level (level B) palliative and hospice care in Helsinki. Identifying the most common compositions enables further researchon standardizing mixtures and centralizing compounding to improve medication safety. This study was conducted as a retrospective medical record review. The data was extracted from the electronic client and patient record system Apotti and consisted of medication administration records of 120 patients receiving special level B palliative and hospice care in Helsinki At-home Hospital and two patient wards in Suursuo Hospital. The data was analyzed with descriptive statistics using Microsoft Excel program. Patient characteristics, including age and ICD-10 diagnosis groups were analyzed. The most common drug combinations used in the mixtures and the combinations with the most variation were identified. Four drug combinations with the most unique compositions were selected for further analysis in which drug concentrations and daily drug doses were analyzed based on continuous infusion rates. 182 drug mixtures including morphine and 147 including oxycodone were identified. A diluent (NaCl 0.9%) was used in 225 mixtures and most often (178/225) the mixtures were diluted into volume of 20 ml. The most frequently used drug combination was comprised of morphine, midazolam, and haloperidol (26.4%), followed by the combination of oxycodone, midazolam, and haloperidol (21.8%). These combinations were also among the four combinations with the most unique compositions with the combination of oxycodone and midazolam and the combination of morphine, midazolam, haloperidol and glycopyrronium. In the four drug combinations with the most unique compositions, the variation was often relatively minor, and the largest variations were observed in opioid components: especially morphine was used in a wide variety of concentrations (2.00–17.91 mg/ml) and daily doses (15–260 mg). Most of the mixtures selected for further review (89/96) were compounded to provide a continuous infusion over a period of four days. In the studied units, mixtures with comparable compositions and features were frequently utilized, suggesting that standardization may be a feasible way to improve medication safety and quality of care in palliative care. As most of the mixtures were administered via PCA, standardization could be particularly advantageous. While it may be possible to standardize and centrally compound mixtures used in this study, more research is needed in several aspects, including physiochemical properties of the mixtures, meeting the clinical requirements in the units, and understanding the underlying factors behind medicine prescribing.