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Opioid tolerance

Frédérique Rodieux, Laszlo Vutskits, Klara M Posfay-Barbe, Walid Habre, Valérie Piguet, Jules A Desmeules, Caroline F Samer
Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children's inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults...
2018: Frontiers in Pharmacology
Adam B King, Matthew D Spann, Patrick Jablonski, Jonathan P Wanderer, Warren S Sandberg, Matthew D McEvoy
BACKGROUND: Patients frequently remain in the hospital after bariatric surgery due to pain, nausea, and inability to tolerate oral intake. Enhanced recovery after surgery (ERAS) concepts address these perioperative complications and therefore improve length of stay for bariatric surgery patients. OBJECTIVES: To determine if ERAS concepts increase the proportion of patients discharged on postoperative day 1. Secondary objectives included mean length of stay, perioperative opioid use, emergency department visits, and readmissions...
February 13, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Samuel Obeng, Yunyun Yuan, Abdulmajeed Jali, Dana E Selley, Yan Zhang
Evidence has shown that downstream signaling by mu opioid receptor (MOR) agonists that recruit β-arrestin2 may lead to the development of tolerance. Also, it has been suggested that opioid receptor desensitization and cyclic AMP overshoot contributes to the development of tolerance and occurrence of withdrawal, respectively. Therefore, studies were conducted with 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ), a MOR selective partial agonist discovered in our laboratory, to characterize its effect on β-arrestin2 recruitment and precipitation of a cyclic AMP overshoot...
March 9, 2018: European Journal of Pharmacology
N Dietis, H Niwa, R Tose, J McDonald, V Ruggieri, M Filaferro, G Vitale, L Micheli, C Ghelardini, S Salvadori, G Calo, R Guerrini, D J Rowbotham, D G Lambert
BACKGROUND AND PURPOSE: Targeting more than one opioid receptor type simultaneously may have analgesic advantages in reduced side effect profile. We have evaluated the mixed MOP (μ, mu) agonist/DOP (δ, delta) antagonist UFP-505 in vitro and in vivo. EXPERIMENTAL APPROACH: We measured receptor density and function in single MOP, DOP and MOP/DOP double expression systems. GTPγ35 S binding, cAMP formation and arrestin recruitment were measured. Antinociceptive activity was measured in vivo using tail withdrawal and paw pressure tests following acute and chronic treatment...
March 10, 2018: British Journal of Pharmacology
Patricia Lavand'homme
PURPOSE OF REVIEW: Cesarean section is the most common surgical procedure performed in the world. Postoperative pain management remains a challenge, particularly in a context of enhanced recovery after surgery. Several barriers related to the specific condition of 'postpartum recovery' may prevent application of effective analgesia in this population. The present review focuses on novel approaches of cesarean section postoperative pain assessment, beyond pain-rating intensity, including objective patient-centered recovery parameters...
March 7, 2018: Current Opinion in Anaesthesiology
Peter Athanasos, Walter Ling, Felix Bochner, Jason M White, Andrew A Somogyi
Objective: Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Design: Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline...
March 5, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Maryann Mazer-Amirshahi, Sergey Motov, Lewis S Nelson
Hydromorphone (HM) is a potent opioid analgesic that is commonly administered in the emergency department (ED) and other acute care settings, such as medical surgical wards. In recent years, there has been a significant increase in the ED administration of HM relative to other opioids. Although HM is an effective analgesic, its use has been commonly implicated in adverse drug events and medication errors. In addition, intravenous HM has potent euphoric effects that may contribute to its abuse liability. There are limited data regarding how acute parenteral administration of opioid analgesics in the setting of high rates of preexisting chronic opioid use (medical or nonmedical) may contribute to or reinforce addictive behavior, making the potential contribution of rising HM administration to subsequent prescription opioid abuse and overdose uncertain...
January 2018: Journal of Opioid Management
Ira J Gottlieb, Deborah R Tunick, Randall J Mack, Stewart W McCallum, Campbell P Howard, Alex Freyer, Wei Du
Objective: This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of an intravenous (IV) nanocrystal formulation of meloxicam in subjects with moderate-to-severe pain following a standardized unilateral bunionectomy. Methods: Fifty-nine subjects aged 18-72 years were randomized to receive doses of either 30 mg (n=20) or 60 mg (n=20) meloxicam IV or placebo (n=19), administered once daily as bolus IV injections over 15-30 seconds (two or three doses)...
2018: Journal of Pain Research
M R Rajagopal
Context: Morphine and fentanyl had so far been the only available opioids in India in step three of the World Health Organization analgesic ladder. Especially for those not tolerating morphine and particularly for those developing neurotoxicity, an inexpensive alternative was essential. Many years of advocacy by palliative care activists have resulted in methadone being now available for sale in India for pain management. However, the characteristic pharmacokinetics and pharmacodynamics of methadone raise potential issues of safety...
January 2018: Indian Journal of Palliative Care
Reham Fahmy, Maha Wasfi, Rania Mamdouh, Kareem Moussa, Ahmed Wahba, Miriam Wittemann, Dusan Hirjak, Katharina M Kubera, Nadine D Wolf, Fabio Sambataro, Robert Christian Wolf
Mindfulness-based interventions (MBI) are increasingly used in the treatment of patients with mental disorders, in particular in individuals presenting with affective disorders or in patients exhibiting abnormal levels of impulsive behavior. MBI have been also offered to patients with substance use disorders, where such treatment options may yield considerable clinical effects. Neural effects associated with MBI have been increasingly acknowledged, but is unknown whether MBI exert specific effects on brain structure in patients with substance use disorders...
February 8, 2018: Addictive Behaviors
Manuel P Pereira, Sonja Ständer
The prevalence of chronic pruritus (CP) in the general population is high and increases with age. Owing to high rates of comorbidities and polypharmacy in patients aged 65 or older, the clinical management of these patients is challenging. Areas covered: In this review, the authors discuss the available therapy options for patients aged ≥ 65 with CP, including emollients for dry skin, topical therapies, phototherapy and systemic agents for CP of various origins. Expert opinion: For multimorbid patients, topical substances and phototherapy constitute the best initial options...
March 1, 2018: Expert Opinion on Pharmacotherapy
Fuyuan Wang, Jingjing Meng, Li Zhang, Timothy Johnson, Chi Chen, Sabita Roy
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo...
February 26, 2018: Scientific Reports
Yusuke Takagi, Etsuko Aruga
In 2010s, several opioids became available in Japan, including methadone, tapentadol and hydromorphone. Methadone was approved in September 2012 by Japanese regulatory authority. Since methadone is positioned as so-called "step 4 opioid" in Japan, it must be prescribed as alternative opioid switched from another of 60mg/day or greater equivalent dose of oral morphine. Diversity of pharmacokinetics among individuals and various drug interactions require close monitoring of adverse events. In spite of these cautions, unique characteristics such as inhibiting N-methyl-D-aspartate(NMDA)and in- ducing internalization/degradation of mu-delta opioid receptor heterodimers underline the value of methadone in opioid switching...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Patrick Grenier, David Wiercigroch, Mary C Olmstead, Catherine M Cahill
Long-term use of opioid analgesics is limited by tolerance development and undesirable adverse effects. Paradoxically, spinal administration of ultra-low-dose (ULD) G-protein-coupled receptor antagonists attenuates analgesic tolerance. Here, we determined whether systemic ULD α2-adrenergic receptor (AR) antagonists attenuate the development of morphine tolerance, whether these effects extend to the cannabinoid (CB1) receptor system, and if behavioral effects are reflected in changes in opioid-induced spinal gliosis...
February 23, 2018: Behavioural Pharmacology
J C Leao, Cdl Marques, Albp Duarte, O P de Almeida, S Porter, L A Gueiros
Chikungunya virus (CHIKV) was first isolated in humans in 1952, following an epidemic in Tanzania. The origin of the name means "to bend forward or become contorted," in reference to the posture adopted by patients due to the joint pain that occurs during the infection. Epidemiology data suggest that by the end of 2015, about 1.6 million people had been infected with CHIKV. The acute period of the disease is characterized by high fever, myalgia, joint pain, and severe and disabling polyarthritis, sometimes accompanied by headache, backache, and maculopapular rash, predominantly on the thorax...
March 2018: Oral Diseases
Sebastiano Mercadante
Breakthrough cancer pain (BTcP) is an episode of severe intensity in patients receiving an adequate treatment with opioids able to provide at least mild analgesia. BTcP is a heterogeneous condition as episodes vary between individuals. The aim of this article is to review the pharmacologic options for the management of BTcP. Areas covered: Recent reviews revealed that transmucosal preparations of fentanyl provided superior and more rapid pain relief as compared to placebo and oral morphine within the first 30 minutes after dosing...
February 26, 2018: Expert Review of Anticancer Therapy
Pedro Barata, Matthew Cooney, Allison Tyler, John Wright, Robert Dreicer, Jorge A Garcia
Background The inhibition of insulin-like growth factor receptor-1 (IGF-1R) induces cell cycle arrest and enhancing the effect of castration by delay of progression of human prostate cancer models. Linsitinib is a small molecule and potent dual inhibitor of IGF-1R and insulin receptor tyrosine kinase activity. We report results of a single-arm, phase II study evaluating the safety and efficacy of linsitinib in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC)...
February 23, 2018: Investigational New Drugs
James M Whedon, Andrew W J Toler, Justin M Goehl, Louis A Kazal
OBJECTIVE: Pain relief resulting from services delivered by doctors of chiropractic may allow patients to use lower or less frequent doses of opioids, leading to reduced risk of adverse effects. The objective of this investigation was to evaluate the association between utilization of chiropractic services and the use of prescription opioid medications. DESIGN: The authors used a retrospective cohort design to analyze health insurance claims data. SETTING: The data source was the all payer claims database administered by the State of New Hampshire...
February 22, 2018: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
Joanna C Jacob, Kensuke Sakakibara, Ryan A Mischel, Graeme Henderson, William L Dewey, Hamid I Akbarali
Oxycodone is a semi-synthetic opioid compound that is widely prescribed, used and abused today, and has a well-established role in shaping the current opioid epidemic. Previously we have shown that tolerance develops to the antinociceptive and respiratory depressive effects of oxycodone in mice, and that a moderate dose of acute ethanol or a PKC inhibitor reversed that tolerance. To investigate further if tolerance was occurring through neuronal mechanisms, our aims for this study were to assess the effects of acute and prolonged oxycodone in isolated dorsal root ganglia (DRG) neurons and to determine if this tolerance was reversed by either ethanol or a PKC inhibitor...
February 21, 2018: Molecular Pharmacology
Ziva D Cooper, Gillinder Bedi, Divya Ramesh, Rebecca Balter, Sandra D Comer, Margaret Haney
Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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