Browsing by Subject "oxycodone"
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(2013)Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channel receptors which are widely distributed in human brain. nAChRs are often expressed pre-synaptically and they modulate the release of other neurotransmitters. nAChRs consist of five subunits: nine different subunits have been identified so far, forming multiple different nAChR subtypes with different pharmacological properties. nAChRs participate extensively in physiological functions and pathophysiological conditions. nAChRs mediate the effects of endogenous agonist, acetylcholine, as well as commonly used substance of abuse, nicotine. Addictive drugs such as nicotine and opioids cause adaptive changes in central nervous system. In addition to binding site of acetylcholine, various allosteric binding sites have been identified in nAChRs. Allosteric ligands are able to modulate the effect of agonist by binding to allosteric binding site. The aim of the experimental part of the pro gradu was to study in vitro interactions of nicotine and three different opioids, codeine, oxycodone and tramadol in SH-SY5Y cells. SH-SY5Y cells express endogenously α3* and α7-nAChRs. Binding assays were performed with radioactive ligand [3H]-epibatidine. Functional interactions of nicotine and the opioids were studied with 86Rb+- efflux assay. Codeine, oxycodone and tramadol exhibited receptor level interactions with nicotine in SH-SY5Y cells. Observed interactions were mediated by nAChRs. The opioids inhibited nAChR activation caused by nicotine without binding to the [3H]-epibatide binding site. Codeine, oxycodone and tramadol appear to affect as weak non-competitive antagonists of nAChRs. These results give further information of nicotine-opioid interactions at receptor level. There are indications that nicotine and opioids also have interactions in vivo, which may be partly explained with these receptor level interactions.
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(2012)Smoking is one of the major causes for premature deaths worldwide. Tobacco smoke contains nicotine, which activates the nicotinic acetylcholine receptors (nAChR) expressed by the human body. nAChRs are part of the cholinergic system and its endogenous neurotransmitter is acetylcholine. The nAChRs are excitatory and the often regulate the release of other neurotransmitters. Nicotine is one of the most addicting compounds known. The rewarding effects of nicotine are mediated through the activation of the mesolimbic dopamine pathway. The mesolimbic pathway is triggered also by the compounds activating the endogenous opioid system thus mediating the rewarding effects and opioid addiction. The nicotine - opioid interactions have been widely studied. It is observed that majority of opioid abusers and patients receiving opioid replacement therapy are smokers. It has been also detected that nicotine releases endogenous opioid peptides in vivo in the brain regions mediating both addiction and analgesia. In addition, the rewarding effect of nicotine attenuates in opioid receptor knock-out rodents. Furthermore, it has been observed that nicotine's rewarding effects can be reduced with opioid receptor antagonists. In order to prevent smoking's negative effects the use opioid antagonists for smoking cessation has been clinically researched with poor results. Many of the opioids in clinical use have diverse and direct interaction with the nAChRs in vitro. E.g. it has been observed that methadone and morphine have an effect on the function of the nAChRs. This may explain partially the smoking behaviour of replacement therapy patients. Opioids are prescribed mainly for the treatment of moderate to intense pain. Nicotine is too found to be analgesic in vivo but in humans its analgesic effect has been questionable. In the experimental part of thesis binding and functional interactions with human's α4β2-nAChR expressed by SH-EP1-hα4β2 cell line was researched with clinically commonly used opioids codeine, oxycodone and tramadol. Competitive binding was studied using [3H]-epibatidine binding assay and the functional effects were studied using 86Rb+-efflux assay. The results suggest that oxycodone and tramadol act as weak competitive antagonists of α4β2-nAChR in vitro in concentrations that are clinically irrelevant. According to the results, however, codeine acts as positive allosteric modulator of α4β2-nAChR potentiating the effects of nicotine in micromolar concentrations. The effect is similar to galantamine, used in treatment of Alzheimer's disease. The clinical relevance of codeine's potentiating nicotine's effect on the function of α4β2-nAChR cannot be estimated according to the results from these studies. Therefore, in order to confirm the results experiments with codeine need to be done in vivo using e.g. α4- and β2-knock-out mice in order to clarify α4β2-nAChR's role in the analgesic and rewarding effects of codeine. However, the results from the experimental part provide valuable information on the interactions of nicotine and opioids. Results from studies conducted with α4β2-nAChRs have not been published enough to determine the importance of the phenomenon in i.a. drug addiction and analgesia.
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(2023)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.
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(2020)Yksi kivunhoidon vaihtoehdoista on kipulääkkeen itseannostelulaitteen käyttö. Kirjallisuuden mukaan itseannostelulaitetta käyttävät potilaat näyttäisivät olevan kivuttomampia ja tyytyväisempiä kivunhoitoonsa verrattuna tavanomaista hoitajan säännöstelemää kipulääkitystä saaviin potilaisiin, mutta kipulääkekulutuksen ero lääkitysmenetelmien välillä vaihtelee. Tämän tutkimuksen tarkoituksena oli verrata opioidikulutusta, mahdollisia haittavaikutuksia ja sairaalahoitoaikaa kipulääkkeen itseannostelulaitetta käyttävien ja tavanomaista kipulääkitystä saavien potilaiden välillä polven tekonivelleikkauksen jälkeen. Lisäksi selvitimme hoitavan henkilökunnan mielipiteitä itseannostelulaitteeseen liittyen. Tutkimuksessa tarkasteltiin retrospektiivisesti 166 potilasta, joille tehtiin polven tekonivelleikkaus spinaalipuudutuksessa. Potilaista 82 sai leikkauksen jälkeen oksikodonia suonensisäisesti itseannostelulaitteen kautta ja 82 kontrollipotilasta sai tavanomaisesti kipulääkitystä hoitajien annostelemana. Ensisijaisena päätemuuttujana oli opioidikulutus 24 tunnin aikana leikkauksen jälkeen. Muita tarkasteltavia muuttujia olivat pahoinvointilääkkeiden käyttö ja sairaalahoitojakson pituus. Lisäksi teetimme kyselytutkimuksen, johon vastasi 31 hoitajaa. Opioidikulutuksessa tai pahoinvointilääkkeiden käytössä 24 tunnin aikana leikkauksen jälkeen ei havaittu merkitsevää eroa ryhmien välillä. Mediaani opioidikulutus morfiiniekvivalenttina annoksena oli itseannosteluryhmässä 41.1 mg (interquartile range, IQR: 39.6 mg) ja kontrolliryhmässä 40.5 mg (IQR: 16.2 mg). Sairaalahoitoajan mediaani oli 2 päivää (IQR: 1 päivä) itseannosteluryhmässä ja 3 päivää (IQR: 1 päivä) kontrolliryhmässä (P=0.02). Kyselytutkimukseen vastanneista hoitajista valtaosa piti laitetta helppokäyttöisenä ja työaikaa säästävänä sekä käyttäisi laitetta mielellään useammilla potilailla. Tuloksien perusteella kipulääkkeen itseannostelulaitteen käyttö polven tekonivelleikkauksen jälkeen ei näyttäisi lisäävän opioidikulutusta hoitajan annostelemaan kipulääkitykseen verrattuna, mutta kipulääkekulutuksen vaihteluväli oli itseannostelulaitteella suurempi. Emme myöskään havainneet eroa haittavaikutuksissa ryhmien välillä, mutta itseannostelulaitetta käyttäneet potilaat mahdollisesti kotiutuvat aikaisemmin.
Now showing items 1-4 of 4