morphine/oxycodone (Q8011) / QRxPharma - LARVOL DELTA

Impact of oxycodone for the treatment of acute postoperative pain in cesarean section: A review. (PubMed, Medicine (Baltimore)) - "These included documents disputed oral oxycodone and patient-controlled intravenous analgesia (PCIA) morphine, compared oral oxycodone and intravenous morphine, investigated sustained-release oral oxycodone and intrathecal morphine, investigated slow release tapentadol and controlled-release oxycodone, investigated ketoprofen, combination of acetaminophen + oxycodone, acetaminophen, and placebo, evaluated oral oxycodone and epidural ropivacaine + sufentanil, evaluated oral oxycodone and PCIA piritramide, evaluated the combination oxycodone + acetaminophen and separately administered oxycodone/acetaminophen, compared the immediate-release oxycodone and controlled-release oxycodone, compared the oral and intravenous oxycodone, disputed PCIA oxycodone or morphine, compared epidural oxycodone and morphine, evaluated PCIA oxycodone, sufentanil or their combination. Oxycodone showed superior or similar postoperative analgesic efficacy compared with other opioids in various..."

Journal • Review • Pain

The effectiveness and safety of the rapid titration strategy of background controlled-release oxycodone hydrochloride for patients with moderate-to-severe cancer pain: A retrospective cohort study. (PubMed, Front Med (Lausanne)) - "258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied...No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P < 0.01), with the most frequent AEs in Group A, lowest in Group B. The rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain."

Journal • Retrospective data • Oncology • Pain

Oxycodone for cancer-related pain. (PubMed, Cochrane Database Syst Rev) - "The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of..."

Journal • Review • Addiction (Opioid and Alcohol) • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

Discovery, Structure-Activity Relationship, and Mechanistic Studies of 1-((3R,4S)-3-((Dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)-2-(2,4,5-trifluorophenyl)ethan-1-one as a Novel Potent Analgesic. (PubMed, J Med Chem) - "Management of moderate to severe pain relies heavily on opioid analgesics such as morphine, oxycodone, and fentanyl in clinics. Mechanistic studies showed that it elicited its analgesic effect via the active metabolite (3R,4S)-10a. The mechanism of (3R,4S)-10a-induced activation of the μ opioid receptor (MOR) was proposed by means of molecular dynamics (MD) simulation."

Journal • Pain

A Promising Chemical Series of Positive Allosteric Modulators of the μ-Opioid Receptor that Enhance the Antinociceptive Efficacy of Opioids but not their Adverse Effects. (PubMed, Neuropharmacology) - "We herein report in vitro and in vivo characterization of two small molecules from a chemical series of MOR PAMs that exhibit: (i) MOR PAM activity and receptor subtype selectivity in vitro, (ii) a differential potentiation of the antinociceptive effect of oxycodone, morphine, and methadone in mouse models of pain that roughly correlates with in vitro activity, and (iii) a lack of potentiation of adverse effects associated with opioid administration, such as somatic withdrawal, respiratory depression, and analgesic tolerance. This series of MOR PAMs holds promise for the development of adjuncts to opioid therapy to mitigate against overdose and opioid use disorders."

Adverse events • Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry • Substance Abuse

Comparison of opioid rotation on pain, symptoms, and daily opioid dose in a supportive care clinic. (PubMed, Ann Palliat Med) - "These findings suggest OR is associated with decreased pain scores without increasing MEDD. Of the agents compared, only rotations to methadone correlated with both a significant reduction in pain scores and in MEDD."

Journal • Oncology • Pain

Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans - pilot study outcomes. (PubMed, Psychopharmacology (Berl)) - "Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Ophthalmology • Pain • Psychiatry • Substance Abuse

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation. (PubMed, Ann Pharmacother) - "A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam. Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements."

Clinical • Journal • Acute Respiratory Distress Syndrome • Anesthesia • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Direct-Acting Antivirals interactions with opioids, alcohol or illicit drugs in HCV-infected patients. (PubMed, Liver Int) - "We discussed the pharmacokinetics (PKs) and pharmacodynamics (PD) of currently prescribed direct antiviral agents (NSA5 inhibitors: daclatasvir, elbasvir, ledipasvir, pibrentasvir, velpatasvir; NS5B inhibitor: sofosbuvir; NS3/4A protease inhibitors: glecaprevir, grazoprevir, voxilaprevir) and most common substances of abuse (opioids: buprenorphine, fentanyl, heroin, methadone, morphine, oxycodone; stimulants: amphetamines, cathinones, cocaine; cannabinoids; ethanol). Based on pharmacological considerations, neither efficacy loss, nor adverse drug event associated with detrimental interaction are expected with opioids, stimulants, cannabinoids, and ethanol. In summary, our literature review shows that the interaction potential of DAA with most opioids and illicit drugs is limited and should not be a hurdle to the initiate DAA."

Clinical • Journal • Review • Hepatitis C • Hepatology • Infectious Disease • Substance Abuse

Prescribing of Nonsteroidal Anti-inflammatory Drugs, Tramadol, and Opioids in Children: Patterns of Its Utilization. (PubMed, J Pharm Bioallied Sci) - "Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged 12 y.o.) with the majority for naproxen (13-15 y.o. (28.2%) and 16-17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12-15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16-17 y.o. Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol."

Clinical • Journal • Pain • Pediatrics

Ten Years of Strong Opioid Analgesics Consumption in Malaysia and Other Southeast Asian Countries. (PubMed, J Pharm Bioallied Sci) - "Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain."

Journal • Oncology • Pain

Les opioïdes par voie orale en remplacement de la codéine pour contrôler la douleur chez les enfants. (PubMed, Paediatr Child Health) - "Les données sur la sécurité et l'efficacité de l'hydromorphone et du tramadol par voie orale chez les enfants sont également limitées. Lorsqu'on y recourt au lieu de la codéine, la morphine par voie orale est l'opiacé dont la sécurité et l'efficacité sont les mieux démontrées chez les enfants. Des recherches devront être réalisées pour explorer d'autres approches relatives aux médicaments opioïdes et non opioïdes, afin d'orienter les traitements analgésiques fondés sur des données probantes qui soulageront la douleur modérée à grave chez les enfants."

Journal • Review

The use of oral opioids to control children's pain in the post-codeine era. (PubMed, Paediatr Child Health) - "There are also limited data on the safety and efficacy of oral hydromorphone and tramadol use for children. Oral morphine is the opiate alternative to codeine for which there is the most evidence of safety and efficacy in children. Research is needed to investigate both other opioids and non-opioid approaches to guide evidence-based analgesic therapy and treatment for moderate-to-severe pain in children."

Clinical • Journal • Review • Pain

EFFECTS OF OPIOID POTENCY AND DURATION OF USE ON ANORECTAL FUNCTION AND SYMPTOM SEVERITY IN PATIENTS WITH OPIOID-INDUCED CONSTIPATION (DDW 2020) - "The opioid potency was categorized weak (tramadol, codeine) to strong (hydrocodone, morphine, oxycodone, hydromorphone, fentanyl)... In a retrospective analysis of OIC patients, opioid potency did not impact anorectal function, sensation or symptom frequency or severity in chronically constipated patients. Duration of opioid use was associated with an abnormal simulated defecation response but no other ARM parameters or BET. These results suggest that the association between opioids and dyssynergic defecation may not be influenced by opioid potency or duration of therapy."

Clinical • Addiction (Opioid and Alcohol) • Constipation

[VIRTUAL] Drug utilization evaluation report for the use of gabapentin and pregabalin at CHI Franciscan (ASHP 2020) - "Purpose: Gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) are FDA approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome...Common opioids were oxycodone, morphine and hydrocodone. Benzodiazepines included diazepam, alprazolam, and clonazepam. Antidepressants noted were mirtazapine, sertraline, escitalopram, and bupropion. Lastly, antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and valproic acid were observed...Benzodiazepine combinations yielded the highest mortality rate of 36%, followed by opioid combinations and cyclobenzaprine, 32% and 30% respectively... Gabapentinoids taken with CNS depressants should be monitored. Patients will be at high risk of developing respiratory depression or increased risk of opioid overdose death. Best safety practices involve initiating gabapentinoids at the lowest dose and providing education to patients to recognize signs and..."

Addiction (Opioid and Alcohol) • Chronic Obstructive Pulmonary Disease • CNS Disorders • Depression • Epilepsy • Immunology • Movement Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain • Psychiatry • Renal Disease • Respiratory Diseases • Restless Legs Syndrome • Sleep Disorder

[VIRTUAL] Assessment of narcotic, sedative, and neuromuscular blocker needs in COVID-19 patients requiring invasive mechanical ventilation (ASHP 2020) - "Narcotics included in this study were fentanyl, hydromorphone, morphine, oxycodone, and methadone...Median daily propofol, midazolam, lorazepam, diazepam, and dexmedetomidine doses (IQ) were 2,721 (1372, 4207)mg, 39 (12, 101)mg, 1.5 (0.6, 3)mg, 12 (8, 19)mg, and 202 (128, 485)mcg, respectively... This analysis suggests that patients with severe COVID-19 who are receiving invasive mechanical ventilation require significant doses of narcotics, sedatives, and paralyzing agents to maintain adequate sedation and ventilation. This study was able to quantify the median daily doses of these agents that were administered to patients with severe COVID-19 infection. The results of this study will help in creating models to predict inventory needs."

Clinical • Anesthesia • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

[VIRTUAL] Trends in hydrocodone combination product exposures reported to California Poison Control System (CPCS) following DEA rescheduling (ASHP 2020) - " We collected monthly exposure data reported to CPCS from 2012 to 2019 and conducted interrupted time series analyses to assess changes in exposures after rescheduling for HCPs, tramadol, oxycodone, morphine, codeine, fentanyl, and heroin. Rescheduling hydrocodone-containing products was associated with a decrease in exposures to prescription opioids reported to CPCS. Our findings suggest that rescheduling may contribute to reducing prescription opioid exposures. Future research could investigate associations between this regulatory change and severe outcomes and whether the same effect was observed in other states that did implement other interventions."

Addiction (Opioid and Alcohol)

Hydromorphone in Cancer Patients-A Retrospective Study (PubMed, Gan To Kagaku Ryoho) - "The administered opioids before switching to hydromorphone were morphine, oxycodone, and tapentadol...No severe adverse effects were observed. The oral hydromorphone extended-release formulation was administered every 24 h, as a tiny tablet formulation that is preferable owing to easy administration and adherence."

Journal • Retrospective data • Gastrointestinal Disorder • Oncology • Pain

Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain. (PubMed, Neuropharmacology) - "In a chemotherapeutic-induced neuropathy pain model SR-17018 is more potent and efficacious than morphine or oxycodone, moreover, this efficacy is retained upon repeated dosing of SR-17018. These findings demonstrate that, with the exception of the tail flick test, SR-17018 retains efficacy upon chronic treatment across several pain models."

Journal • Preclinical • Pain

How successful is parenteral oxycodone for relieving terminal cancer dyspnea compared with morphine? A multicenter prospective observational study. (PubMed, J Pain Symptom Manage) - "Parenteral oxycodone may be equally effective and safe as morphine in the treatment of terminal dyspnea in cancer patients. Future randomized controlled trials should confirm the efficacy and safety of opioids other than morphine for terminal dyspnea."

Clinical • Journal • Observational data • Lung Cancer • Oncology • Palliative care • Solid Tumor

Chronic Pain Treatment Strategies in Parkinson's Disease. (PubMed, Neurol Int) - "One of the most used combination drugs for PD is Levodopa-Carbidopa, a dopamine precursor that is converted to dopamine by the action of a naturally occurring enzyme called DOPA decarboxylase. Pramipexole, a D2 dopamine agonist, and apomorphine, a dopamine agonist, and Rotigotine, a dopamine receptor agonist, have showed efficacy on PD-associated pain...Opioids and opioid-like medications such as oxycodone, morphine, tramadol, and codeine are also commonly employed in treatment of chronic pain in PD. Other opioid related medications such as Tapentadol, a central-acting oral analgesic with combined opioid and noradrenergic properties, and Targinact, a combination of the opioid agonist oxycodone and the opioid antagonist naloxone have shown improvement in pain. Anticonvulsants such as gabapentin, pregabalin, lamotrigine, carbamazepine and tricyclic antidepressants (TCAs) can be trialed when attempting to manage chronic pain in PD...A treatment plan can be devised that may..."

Journal • Review • CNS Disorders • Mood Disorders • Movement Disorders • Musculoskeletal Diseases • Neuralgia • Pain • Parkinson's Disease • Peripheral Neuropathic Pain • Psychiatry

Opioids for chronic non-cancer neuropathic pain. An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least four weeks duration. (PubMed, Eur J Pain) - "Some opioids provided a short-term substantial pain relief in highly selected patients in some neuropathic pain syndromes."

Journal • Retrospective data • Review • Diabetic Neuropathy • Musculoskeletal Pain • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

Real-World Data on Nonmedical Use of Tramadol from Patients Evaluated for Substance Abuse Treatment in the NAVIPPRO Addiction Severity Index-Multimedia Version (ASI-MV) Network. (PubMed, Drug Saf) - "Tramadol had a significantly lower rate of NMU than comparator opioids and was less likely to be diverted or used via higher-risk non-oral routes. These findings support previous evaluations by WHO and the United States Drug Enforcement Agency that concluded that tramadol has a low potential for abuse."

Clinical • Journal • Real-World Evidence • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies. (PubMed, Front Immunol) - "A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "opioids," "Natural killer cells," "cytokines," and "lymphocytes." The results achieved concerning the effects of fentanyl, methadone, oxycodone, buprenorphine, remifentanil, tramadol, and tapentadol on immune responses in animal studies, in healthy volunteers and in patients are reported. With some limitations due to the different methods used to measure immune system parameters, the large range of opioid doses and the relatively scarce number of participants in the available studies, we conclude that it is not correct to generalize immunosuppression as a common side effect of all opioid molecules."

Journal • Review • Immune Modulation • Inflammation

The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis. (PubMed, Sci Rep) - "Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary."

Journal • Retrospective data • Oncology • Pain