Browsing by Subject "oxycodone"

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  • Lahtinen, Katarina; Reponen, Elina; Vakkuri, Anne; Palanne, Riku; Rantasalo, Mikko; Linko, Rita; Madanat, Rami; Skants, Noora (2021)
    Objectives: Severe post-operative pain is common after total knee arthroplasty. Patient-controlled analgesia is an alternative method of pain management, whereby a patient administers his or her own pain medication. Patients seem to prefer this method over nurse-administered analgesia. However, it remains unclear whether patients using patient-controlled analgesia devices use higher or lower doses of opioids compared to patients treated with oral opioids. Methods: This retrospective study examined 164 patients undergoing total knee arthroplasty. Post-operatively, 82 patients received oxycodone via intravenous patient-controlled analgesia devices, while the pain medication for 82 patients in the control group was administered by nurses. The main outcome measure was the consumption of intravenous opioid equivalents within 24 h after surgery. Secondary outcome measures were the use of anti-emetic drugs and the length of stay. Furthermore, we evaluated opioid-related adverse event reports. Results: The consumption of opioids during the first 24 h after surgery and the use of anti-emetic drugs were similar in both groups. The median opioid dose of intravenous morphine equivalents was 41.1 mg (interquartile range (IQR): 29.5-69.1 mg) in the patient-controlled analgesia group and 40.5 mg (IQR: 32.4-48.6 mg) in the control group, respectively. The median length of stay was 2 days (IQR: 2-3 days) in the patient-controlled analgesia group and 3 days (IQR: 2-3 days) in the control group (p=0.02). The use of anti-emetic drugs was similar in both groups. Conclusions: The administration of oxycodone via intravenous patient-controlled analgesia devices does not lead to increased opioid or anti-emetic consumptions compared to nurse-administered pain medication after total knee arthroplasty. Patient-controlled analgesia might lead to shortened length of stay.
  • Lilius, T.; Kangas, E.; Niemi, M.; Rauhala, P.; Kalso, E. (2018)
    Background: Ketamine attenuates morphine tolerance by antagonising N-methyl-D-aspartate receptors. However, a pharmacokinetic interaction between morphine and ketamine has also been suggested. The interaction between oxycodone and ketamine is unclear. We studied the effects of ketamine and norketamine on the attenuation of morphine and oxycodone tolerance focusing on both the pharmacodynamic and pharmacokinetic interactions. Methods: Morphine 9.6 mg day(-1) or oxycodone 3.6 mg day(-1) was delivered to SpragueeDawley rats by subcutaneous pumps. Once tolerance had developed, the rats received subcutaneous injections of ketamine or norketamine. Tail-flick, hot-plate, and rotarod tests were performed. Drug concentrations were measured with high-performance liquid chromatographyetandem mass spectrometry. Results: Anti-nociceptive tolerance to morphine and oxycodone developed similarly by Day 6. Acute ketamine 10 mg kg(-1) and norketamine 30 mg kg(-1) attenuated morphine tolerance for 120 and 150 min, respectively, whereas in oxycodonetolerant rats the effect lasted only 60 min. Both ketamine and norketamine increased the brain and serum concentrations of morphine, and inhibited its metabolism to morphine-3-glucuronide, whereas oxycodone concentrations were not changed. Morphine, but not oxycodone, pretreatment increased the brain and serum concentrations of ketamine and norketamine. Ketamine, but not norketamine, significantly impaired the motor coordination. Conclusions: Ketamine and norketamine attenuated morphine tolerance more effectively than oxycodone tolerance. Ketamine and norketamine increased morphine, but not oxycodone brain concentrations, which may partly explain this difference. Norketamine is effective in attenuating morphine tolerance with minor effects on motor coordination. These results warrant pharmacokinetic studies in patients who are co-treated with ketamine and opioids.
  • Valitalo, Pyry; Kokki, Merja; Ranta, Veli-Pekka; Olkkola, Klaus T.; Hooker, Andrew C.; Kokki, Hannu (2017)
    Purpose The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. Methods Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. Results The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. Conclustions Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.
  • Havia, Mari (Helsingfors universitet, 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.
  • Viisanen, Hanna; Lilius, Tuomas O.; Sagalajev, Boriss; Rauhala, Pekka; Kalso, Eija; Pertovaara, Antti (2020)
    Descending facilitatory circuitry that involves the rostroventromedial medulla (RVM) exerts a significant role in the development of antinociceptive tolerance and hyperalgesia following chronic morphine treatment. The role of the RVM in the development of antinociceptive tolerance to oxycodone, another clinically used strong opioid. is not yet known. Ketamine, an N-methyl-o-aspartate (NMDA) receptor antagonist, attenuates opioid antinociceptive tolerance, but its effect on RVM cell discharge in opioid-tolerant animals is not known. Here, we compared chronic effects of morphine and oxycodone on the discharge properties of RVM cells and attempted to attenuate chronic treatment-induced changes with ketamine. Parallel recordings of RVM cell discharge and limb withdrawal response were performed under light pentobarbital anesthesia in male rats following sustained systemic treatment with morphine or oxycodone at equianalgesic doses. Ongoing activity and the response to noxious heat and pinch were determined in pronociceptive RVM ON-cells and antinociceptive OFF-cells on the sixth treatment day. Proportions of RVM cell types were not changed. Chronic oxycodone induced antinociceptive tolerance both in limb withdrawal and RVM cell activity. Chronic morphine induced antinociceptive tolerance in limb withdrawal that was accompanied by pronociceptive heat response changes in RVM ON- and OFF-cells. A behaviorally subantinociceptive dose of acute ketamine reversed antinociceptive tolerance both to morphine and oxycodone in limb withdrawal and reversed the chronic morphine-induced pronociceptive discharge changes in RVM cells. The results indicate that an NMDA receptor-dependent descending pronociceptive circuitry involving the RVM has an important role in behavioral antinociceptive tolerance to morphine but not oxycodone. NEW & NOTEWORTHY Morphine and oxycodone are two clinically used strong opioids. Chronic treatment with oxycodone as well as morphine can lead to analgesic tolerance and paradoxical hyperalgesia. Here we show that an N-methyl-n-aspartate receptor-dependent pronociceptive change in discharge properties of rostroventromedial medullary neurons controlling spinal nociception has an important role in antinociceptive tolerance to morphine but not oxycodone. Interestingly, chronic oxycodone did not induce pronociceptive changes in the rostroventromedial medulla.
  • Meijer, Juri (Helsingfors universitet, 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.
  • Lahtinen, Katarina (Helsingin yliopisto, 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.