- Opioid and benzodiazepine use during therapeutic hypothermia in encephalopathic neonates. [Journal Article]J Perinatol 2019JP
- CONCLUSIONS: Sedation/analgesia during therapeutic hypothermia is prevalent but not uniform across centers. Prospective studies are needed to assess if exposure independently predicts intensity and duration of physiologic support.
- Fatalities in poisoned patients managed by medical toxicologists. [Journal Article]Clin Toxicol (Phila) 2019; :1-4CT
- CONCLUSIONS: Most ToxIC registry exposures resulting in death involve intentional exposure, without sex predominance. One in 10 fatalities involved a child. Analgesics, non-opioids, and opioids are the most commonly implicated agents in both fatal and non-fatal intoxications, which highlights the centrality of these agents as major sources of both morbidity and mortality.
- Child and adolescent benzodiazepine exposure and overdose in the United States: 16 years of poison center data. [Journal Article]Clin Toxicol (Phila) 2019; :1-7CT
- CONCLUSIONS: The rate and severity of reported pediatric benzodiazepine exposure is increasing over time. Adolescent exposures are of specific concern, as co-ingestion and intentional abuse were found to be more common in this group. Medical providers and caretakers should be cognizant of this growing epidemic to avoid preventable harm to adolescents, young children, and infants.
- Real-world use of the sufentanil sublingual tablet system for patient-controlled management of acute postoperative pain: a prospective noninterventional study. [Journal Article]Curr Med Res Opin 2019; :1CM
- CONCLUSIONS: The SSTS is a valuable option for real-life POPM and is effective in a wide range of surgical procedures. Trial registration: European Union electronic Register of Post-Authorization Studies (EU PAS Register) number: EUPAS14689.
- A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor. [Journal Article]Proc Natl Acad Sci U S A 2019PN
- An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (K i low micromolar) μ-opioid agonists, which led to the design of bilorphin, a potent and selective μ-opioid receptor (MOPr) agonist (K i 1.1 nM). In sha…
An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (K i low micromolar) μ-opioid agonists, which led to the design of bilorphin, a potent and selective μ-opioid receptor (MOPr) agonist (K i 1.1 nM). In sharp contrast to all-natural product opioid peptides that efficaciously recruit β-arrestin, bilorphin is G protein biased, weakly phosphorylating the MOPr and marginally recruiting β-arrestin, with no receptor internalization. Importantly, bilorphin exhibits a similar G protein bias to oliceridine, a small nonpeptide with improved overdose safety. Molecular dynamics simulations of bilorphin and the strongly arrestin-biased endomorphin-2 with the MOPr indicate distinct receptor interactions and receptor conformations that could underlie their large differences in bias. Whereas bilorphin is systemically inactive, a glycosylated analog, bilactorphin, is orally active with similar in vivo potency to morphine. Bilorphin is both a unique molecular tool that enhances understanding of MOPr biased signaling and a promising lead in the development of next generation analgesics.
- Persistent and Chronic Postoperative Opioid Use in a Cohort of Patients with Oral Tongue Squamous Cell Carcinoma. [Journal Article]Pain Med 2019PM
- CONCLUSIONS: Patients with oral tongue cancers have a high risk of developing persistent and chronic postsurgical opioid use.
- Association between buprenorphine/naloxone and high-dose opioid analgesic prescribing in Kentucky, 2012-2017. [Journal Article]Drug Alcohol Depend 2019; 205:107606DA
- CONCLUSIONS: Our results indicate a significant reciprocal relationship between HDOAP and buprenorphine/naloxone prescribing and a clinically meaningful effect of buprenorphine/naloxone prescribing on reducing HDOAP. Future studies on buprenorphine/naloxone treatment expansion should take into account this bi-directional association in the context of longitudinal data and evaluate for public health benefits beyond the reduction of HDOAP.
- Insuffisance surrénalienne secondaire : actualités diagnostiques et thérapeutiques: News in diagnosis and therapeutics of secondary adrenal insufficiency. [Journal Article]Ann Endocrinol (Paris) 2019; 80 Suppl 1:S1-S9AE
- Immunotherapy and opioids treatment are new causes of secondary adrenal insufficiency (SAI). Prevalence of SAI with immunotherapy is more frequent with combined therapy (8% vs 4 to 10% with CTLA4 blocking antibody and 1% with PD1 blocking antibody). Although hypophysitis are more frequently observed with CTLA4 blocking antibody, some cases of Isolated SAI have been reported in patients treated by…
Immunotherapy and opioids treatment are new causes of secondary adrenal insufficiency (SAI). Prevalence of SAI with immunotherapy is more frequent with combined therapy (8% vs 4 to 10% with CTLA4 blocking antibody and 1% with PD1 blocking antibody). Although hypophysitis are more frequently observed with CTLA4 blocking antibody, some cases of Isolated SAI have been reported in patients treated by PD1 blocking antibody. SAI could be transient, requiring long-term monitoring. The use of opioid analgesics is increasing in many countries, thus becoming a public health problem. Prevalence of opioid-related SAI is unclear but recent prospective studies reveal a prevalence between 5 and 20%. The main risk factor to develop this pathology is morphine-equivalent daily dose. Diagnosis relies on 8.00 am plasma cortisol measurement and cortisol increase after Synacthen® administration. Recent cortisol immuno-assays, in agreement with mass spectrometry, give lower reference values, encouraging reevaluation of the current cut-off of 500 nmol/L. New modified-release hydrocortisone preparations have been recently developed to better mimic the physiological cortisol rhythm and to improve compliance in adrenocortical deficient patients. Nowadays, continuous subcutaneous hydrocortisone infusion seems to be a unique replacement therapy allowing adequate circadian biorhythm but should be restricted to specific patients due to the complexity of this substituting strategy. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.
- Inpatient pain management in sickle cell disease. [Journal Article]Am J Health Syst Pharm 2019AJ
- CONCLUSIONS: SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4-7) or severe (grade 8-10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported.Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC.
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- Use and Efficacy of Analgesic Agents in Sheep (Ovis aries) Used in Biomedical Research. [Journal Article]J Am Assoc Lab Anim Sci 2019JA
- Sheep (Ovis aries) are widely used as large animal models in biomedical research. However, current literature on the use ofanalgesics in sheep generally focuses on an industry or farm level of use. This structured review evaluates use and efficacy of analgesics administered to sheep in a biomedical research setting. Electronic databases were searched with terms related to analgesia in research sh…
Sheep (Ovis aries) are widely used as large animal models in biomedical research. However, current literature on the use ofanalgesics in sheep generally focuses on an industry or farm level of use. This structured review evaluates use and efficacy of analgesics administered to sheep in a biomedical research setting. Electronic databases were searched with terms related to analgesia in research sheep. After application of exclusion criteria, 29 peer-reviewed publications were evaluated from 1995 to 2018. Drugs used for analgesia in sheep include opioids, α2 agonists, NSAID, local anesthetics, NMDA receptor antagonists, and calcium channel blockers. Opioid agonists have previously been considered short acting and of questionable efficacy in sheep, but newer modalities may provide effective analgesia. NSAID may exhibit an analgesic effect only when inflammatory pain is present and may not be beneficial for use in acute pain models. α2 agonists provide effective yet short-lived analgesia; however, side effects are of concern. Local anesthetics were previously widely used as stand-alone agents, as alternatives tothe use of general anesthetics in sheep. These agents have since fallen out of favor as sole agents. Despite this, they provide a valuable analgesic effect when used as adjuncts to general anesthetic regimes. The NMDA antagonist ketamine provided good analgesia and is likely underutilized as an analgesic agent in sheep. Future controlled studies should further evaluate the analgesic properties of ketamine in sheep.