Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37.567
Filtrar
1.
Trials ; 22(1): 632, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530881

RESUMO

OBJECTIVES: We aim to study the effect of epidural morphine as a means to reduce high respiratory drive in COVID 19 patients on non-invasive ventilation (NIV)-primary end point-and to study its effect on respiratory parameters, subjective patient comfort, rates of endotracheal intubation, duration of mechanical ventilation and mortality. TRIAL DESIGN: Parallel group, randomised, double blind, single centre placebo control trial. Allocation ratio 1:1, superiority trial PARTICIPANTS: Trial site and population-COVID ICU patients in the All India Institute of Medical Sciences (AIIMS) Bhubaneswar, Odisha, India Inclusion and exclusion criteria Inclusion criteria Adult patients on NIV with COVID-19 Exclusion criteria Metabolic acidosis HCO3-< 16 and pH < 7.2. Severe hypoxemia warranting cessation of NIV and intubation, non-acceptance of NIV and proven sepsis. Technical difficulty for epidural catheterization, coagulation abnormalities, low respiratory drive and EOL orders. Sources or methods of recruitment-daily discussion at 8 am of new admissions to COVID ICU on NIV-consenting adult patients with COVID19 on NIV and high respiratory drive; not meeting exclusion criteria will be recruited for the trial and randomised. INTERVENTION AND COMPARATOR: Patients of both groups will be turned to a lateral or sitting position (as comfortable), and an injection of local anaesthetic be given at lumbar 2-3/3-4 space. In the intervention group, an epidural catheter will be inserted using aseptic technique and fixed to the skin. The control group will have a sham catheter fixed exactly like in the intervention group, but not entering the epidural space. The intervention group will be administered injection morphine sulphate once every 18-24 h into the epidural space. The doses will be escalated daily (5-10 mg), titrated to effect: escalation limited by hypoventilation resulting in respiratory acidosis (pH < 7.2). The intervention will continue for a minimum of 2 doses and a maximum of 5 doses (96 h) of morphine. It will be stopped if the epidural catheter gets dislodged before the second dose or the patient is weaned off non-invasive ventilation to high flow mask for a continuous period of 24 h or requires endotracheal intubation. The patient will be followed up till death or 28 days after ICU discharge. MAIN OUTCOMES: Primary outcome-diaphragm thickening index fraction (average of minimum 3 readings) Secondary outcomes-ventilator parameters, sedation and pain scores, subjective comfort and dyspnoea scores, time to intubation, length of stay on NIV and 28-day mortality Timing of outcome assessment-every 8th hour assessment for 24 h after the last dose of epidural morphine or 120 h whichever is greater RANDOMISATION: A central random number list will be kept with the study research assistant. She will randomise according to the numbers available in the list using an allocation ratio of 1:1. An opaque sealed envelope concealing the allotted randomisation code will be dispatched to the ICU team. BLINDING (MASKING): The assessor, patient, nurses and physicians will be blind to group allocation. One member of the team not involved in research will administer the intervention. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twenty-five patients per group; 50 patients total TRIAL STATUS: Protocol version 1. Not recruiting yet. Recruitment to begin by 24 July 2021 and end by 31 August 2022 TRIAL REGISTRATION: Central Trials Registry India CTRI CTRI/2021/07/035093 . Registered on 23 July 2021. Prospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Adulto , Espaço Epidural , Humanos , Morfina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
2.
J Opioid Manag ; 17(7): 109-118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520032

RESUMO

Opioids are an important tool in the treatment of pain, but opioid overdose has become a serious health issue. Most opioid-related deaths are caused by respiratory depression, and the risk of respiratory depression is compounded because of the risks of abuse and diversion, which makes the need for safer opioids even more urgent. However, the atypical opioids (buprenorphine, tramadol, and tapentadol), with mechanisms of action not purely driven by µ-opioid receptor agonism, may be safer than conventional opioids, eg, morphine, oxycodone, and fentanyl. The purpose of this narrative review is to describe the clinical and experimental evidence regarding opioid-induced respiratory depression in the context of the mechanisms of action of the atypical opioids. Among the atypical opioids, tramadol has an advantage of being a Schedule IV drug, and thus having a relatively low abuse potential-but its effects, including its effect on respiratory drive, are dependent on cytochrome P450 2D6 metabolizer status. Tapentadol appears to affect respiratory drive, but this has not been well investigated. Buprenorphine is a Schedule III drug, thus having less abuse potential than the majority of opioids. Experimentally, a ceiling effect on the respiratory depression has been reported with intravenous buprenorphine. In addition, experimental hypercapnic stress in healthy volunteers demonstrated no respiratory depression following the administration of a single dose of the buccal film formulation of buprenorphine when compared with placebo. Overall, the data suggest that atypical opioids may be a safer option than conventional opioids for the treatment of pain.


Assuntos
Analgésicos Opioides , Buprenorfina , Analgésicos Opioides/efeitos adversos , Fentanila , Humanos , Morfina , Oxicodona
3.
Ned Tijdschr Tandheelkd ; 128(9): 441-450, 2021 Sep.
Artigo em Holandês | MEDLINE | ID: mdl-34490769

RESUMO

To alleviate acute dental pain, dentists and dental specialists frequently prescribe analgesics to patients, either on prescription or not. In order to effectively manage dental pain, it is advisable to follow a step-by-step plan based on the WHO analgesic ladder: step 1, start with acetaminophen step 2, add an NSAID (e.g. ibuprofen, diclofenac, naproxen); step 3, add a weak opioid (e.g. tramadol) in combination with acetaminophen or an NSAID; step 4, replace a weak opioid with a strong opioid (e.g. morphine or oxycodone). A dentist in general practice or a dental specialist needs to know, the mechanism of action and the most important interactions, contraindications and adverse effects of each of these groups of medications. Attention is needed when prescribing analgesics to risk groups such as frail elderly, pregnant and lactating women, and children.


Assuntos
Lactação , Tramadol , Idoso , Analgésicos , Analgésicos Opioides/efeitos adversos , Criança , Feminino , Humanos , Morfina , Gravidez
4.
J Chem Inf Model ; 61(8): 3964-3977, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34351148

RESUMO

Opioid drug binding to specialized G protein-coupled receptors (GPCRs) can lead to analgesia upon activation via downstream Gi protein signaling and to severe side effects via activation of the ß-arrestin signaling pathway. Knowledge of how different opioid drugs interact with receptors is essential, as it can inform and guide the design of safer therapeutics. We performed quantum and classical mechanical computations to explore the potential energy landscape of four opioid drugs: morphine and its derivatives heroin and fentanyl and for the unrelated oliceridine. From potential energy profiles for bond twists and from interactions between opioids and water, we derived a set of force-field parameters that allow a good description of structural properties and intermolecular interactions of the opioids. Potential of mean force profiles computed from molecular dynamics simulations indicate that fentanyl and oliceridine have complex energy landscapes with relatively small energy penalties, suggesting that interactions with the receptor could select different binding poses of the drugs.


Assuntos
Morfina , Preparações Farmacêuticas , Analgésicos Opioides , Heroína , Receptores Opioides mu , Compostos de Espiro , Tiofenos
5.
Psychopharmacology (Berl) ; 238(10): 2729-2741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34405254

RESUMO

RATIONALE: An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life. METHODS: On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1 ml/kg), naloxone (1 mg/kg), and acute morphine (1, 3, 5 mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance. As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5 mg/kg morphine for 5 days and then naloxone in the last day of the experiment (day 6). RESULTS: Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone. CONCLUSION: The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood.


Assuntos
Morfina , Efeitos Tardios da Exposição Pré-Natal , Analgésicos Opioides , Animais , Atenção , Feminino , Comportamento Impulsivo , Masculino , Gravidez , Ratos
6.
Neuropsychopharmacology ; 46(11): 1990-1999, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34341495

RESUMO

The anterior cingulate cortex (ACC) is implicated in many pathologies, including depression, anxiety, substance-use disorders, and pain. There is also evidence from brain imaging that the ACC is hyperactive during periods of opioid withdrawal. However, there are limited data contributing to our understanding of ACC function at the cellular level during opioid withdrawal. Here, we address this issue by performing ex vivo electrophysiological analysis of thick-tufted, putative dopamine D2 receptor expressing, layer V pyramidal neurons in the ACC (ACC L5 PyNs) in a mouse model of spontaneous opioid withdrawal. We found that escalating doses of morphine (20, 40, 60, 80, and 100 mg/kg, i.p. on days 1-5, respectively) injected twice daily into male C57BL/6 mice evoked withdrawal behaviors and an associated withdrawal-induced mechanical hypersensitivity. Brain slices prepared 24 h following the last morphine injection showed increases in ACC L5 thick-tufted PyN-intrinsic membrane excitability, increases in membrane resistance, reductions in the rheobase, and reductions in HCN channel-mediated currents (IH). We did not observe changes in intrinsic or synaptic properties on thin-tufted, dopamine D1-receptor-expressing ACC L5 PyNs recorded from male Drd1a-tdTomato transgenic mice. In addition, we found that chemogenetic inhibition of the ACC blocked opioid-induced withdrawal and withdrawal-induced mechanical hypersensitivity. These results demonstrate that spontaneous opioid withdrawal alters neuronal properties within the ACC and that ACC activity is necessary to control behaviors associated with opioid withdrawal and withdrawal-induced mechanical hypersensitivity. The ability of the ACC to regulate both withdrawal behaviors and withdrawal-induced mechanical hypersensitivity suggests overlapping mechanisms between two seemingly distinguishable behaviors. This commonality potentially suggests that the ACC is a locus for multiple withdrawal symptoms.


Assuntos
Hiperalgesia , Síndrome de Abstinência a Substâncias , Analgésicos Opioides , Animais , Giro do Cíngulo , Hiperalgesia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina , Ratos , Ratos Sprague-Dawley
7.
Life Sci ; 283: 119866, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352257

RESUMO

AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation.


Assuntos
Lipase/metabolismo , Morfina/farmacologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Triglicerídeos/biossíntese , Animais , Linhagem Celular , Masculino , Camundongos , Morfina/farmacocinética , Miocárdio/patologia , Miócitos Cardíacos/patologia , Fosforilação/efeitos dos fármacos
8.
Environ Sci Pollut Res Int ; 28(38): 52675-52688, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453251

RESUMO

We aimed to review the literature to find the specific effect of opioids on the activity of cholinesterase (ChE) enzyme which plays a substantial role in the functioning of cholinergic system. Literature search was performed by two independent reviewers in order to find relevant articles about the changes in the activity of ChE in mice or rat following opioid administration. Based on findings from literature review, opioid administration is able to induce cholinergic modulation via decreasing or increasing the activity of ChE enzyme. However, the degree of variation of ChE in various brain regions is different. No gender differences was reported in the effect of opioids on ChE activity. Although chronic opioid administration may decrease enzyme function, ChE activity might be unchanged following opioid withdrawal using naloxone or the development of tolerance. Opioid type affects whether or not naloxone can reverse the changes of ChE. Direct inhibitory action of morphine and the other opioid ligands believed responsible for the decrease in the ChE activity. Moreover, the potency of codeine to induce allosteric enhancement of acetylcholine receptor signaling might be involved in the cholinergic modulation of codeine and other opioids. Animal studies on rat and mice showed that opioids may change the activity of ChE. These changes can pertain an increase or decrease in enzyme activity; as there might be no change. The type of opioid used may have an effect on the cholinergic modulation. It is beneficial to conduct cross-sectional and cohort studies on addicted individuals, especially opium abusers, to find the precise association of opioids with alterations in human acetyl cholinesterase or butyrylcholinesterase. Simulation studies can also examine the structure-function relationships and provide important details to better understand the mechanism of action of opioid compounds on ChE activity. In addition, understanding how opioids impact ChE activity may help perform proper interventions for drug abstinence.


Assuntos
Analgésicos Opioides , Butirilcolinesterase , Animais , Codeína , Estudos Transversais , Camundongos , Morfina/farmacologia , Ratos
9.
Biomed Khim ; 67(4): 323-330, 2021 Jul.
Artigo em Russo | MEDLINE | ID: mdl-34414890

RESUMO

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.


Assuntos
Morfina , Neurotransmissores , Animais , Encéfalo , Etanol/toxicidade , Ratos , Serotonina
10.
Rev Med Liege ; 76(7-8): 614-619, 2021 Jul.
Artigo em Francês | MEDLINE | ID: mdl-34357714

RESUMO

Intracerebroventricular (ICV) infusion of morphine is a well-known technique to relieve intractable neoplasic pain when conventional analgesic strategies reach their limits. Through this case report, we present indications, assets, and drawbacks of this procedure in such conditions. We also describe the adaptation of the systemic analgesic treatment to allow discharge from the hospital to home settings. Thanks to the ICV infusion of a mixture of morphine, bupivacaine and clonidine, the patient was weaned from oral opioid medications and reached an acceptable level of comfort. This allowed him to be discharged from the hospital to go back home with a specific setting of mobile palliative care structure. The patient's family followed training about the device to prevent any technical trouble and to react in case of unwanted events.


Assuntos
Clonidina , Dor Intratável , Analgésicos Opioides/uso terapêutico , Bupivacaína/uso terapêutico , Clonidina/uso terapêutico , Humanos , Infusões Intraventriculares , Masculino , Morfina/uso terapêutico , Dor Intratável/tratamento farmacológico , Dor Pós-Operatória , Cuidados Paliativos
11.
ACS Chem Neurosci ; 12(16): 3124-3139, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34351126

RESUMO

The clinical treatment of chronic postoperative pain (CPSP) remains challenging. The side effects of chronic morphine treatment limit its clinical application. MEL-0614, a novel endomorphin analogue that is highly selective and agonistic for µ opioid receptor (MOR), produces a more powerful analgesic effect than that of morphine. In this study, we explored the difference in antinociceptive tolerance and related mechanisms between MEL-0614 and morphine in CPSP induced in a skin/muscle incision and retraction (SMIR) mice model. We found that acute administration of MEL-0614 (1, 3, 5, and 10 nmol, i.t.) produced a dose-dependent analgesic effect that was superior to that of morphine in the SMIR mice model. Long-term MEL-0614 treatment (10 nmol, i.t.) did not induce tolerance compared with morphine. Notably, tolerance induced by morphine could be greatly prevented and/or inhibited via cross-administration or coadministration between MEL-0614 and morphine. In addition, MEL-0614 accelerated the recovery of postoperative pain, whereas morphine aggravated postoperative pain and prolonged its recovery time regardless of preoperative or postoperative treatment. In addition, MEL-0614 did not activate microglia and the P2X7R signaling pathway and showed reduced expression iba1 and P2X7R compared with that observed after morphine administration. Release of inflammatory factors was induced by continued administration of morphine during SMIR surgery, but MEL-0614 did not promote the activation of inflammatory factors. Our results showed that MEL-0614 has superior analgesic effects in CPSP and leads to tolerance to a lesser degree than morphine. Further, MEL-0614 may be used as a promising treatment option for the long-term treatment in CPSP.


Assuntos
Morfina , Dor Pós-Operatória , Analgésicos Opioides/farmacologia , Animais , Tolerância a Medicamentos , Camundongos , Morfina/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Receptores Opioides mu , Receptores Purinérgicos P2X7 , Transdução de Sinais
12.
Cochrane Database Syst Rev ; 7: CD002059, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231914

RESUMO

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodevelopmental disability. There was low certainty evidence for no difference in days hospitalisation or days treatment. This study did not report adverse events. Opioid versus diazepam: there was a reduction in treatment failure from use of an opioid (RR 0.43, 95% CI 0.23 to 0.80; 2 studies, 86 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study of 34 infants comparing methadone versus diazepam reported no difference in days hospitalisation or days treatment (very low certainty evidence). Adverse events were not reported. Opioid versus phenobarbital: there was a reduction in treatment failure from use of an opioid (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants; moderate certainty evidence). Subgroup analysis found a reduction in treatment failure in trials titrating morphine to ≧ 0.5 mg/kg/day (RR 0.21, 95% CI 0.10 to 0.45; 3 studies, 230 infants), whereas a single study using morphine < 0.5 mg/kg/day reported no difference compared to use of phenobarbital (subgroup difference P = 0.05). Neonatal or infant mortality and neurodevelopmental disability were not reported. A single study (111 infants) of paregoric versus phenobarbital reported seven infants with seizures in the phenobarbital group, whereas no seizures were reported in two studies (170 infants) comparing morphine to phenobarbital. There was no difference in days hospitalisation or days treatment. A single study (96 infants) reported no adverse events in either group. Opioid versus chlorpromazine: there was a reduction in treatment failure from use of morphine versus chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants; moderate certainty evidence). No seizures were reported in either group. There was low certainty evidence for no difference in days treatment. This trial reported no adverse events in either group. None of the included studies reported time to control of NAS. Data for duration and severity of NAS were limited, and we were unable to use these data in quantitative synthesis. AUTHORS' CONCLUSIONS: Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.


Assuntos
Entorpecentes/uso terapêutico , Síndrome de Abstinência Neonatal/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Buprenorfina/uso terapêutico , Clorpromazina/uso terapêutico , Clonidina/uso terapêutico , Diazepam/uso terapêutico , Humanos , Hipnóticos e Sedativos/uso terapêutico , Recém-Nascido , Metadona/uso terapêutico , Morfina/uso terapêutico , Ópio/uso terapêutico , Fenobarbital/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Clin Cardiol ; 44(9): 1216-1224, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34236089

RESUMO

While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta-analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in-hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7-day all-cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30-day all-cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short-term death (in the hospital or within 7 days) in patients with AHF, the risk of long-term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.


Assuntos
Insuficiência Cardíaca , Morfina , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Mortalidade Hospitalar , Humanos , Morfina/efeitos adversos
14.
Neurosci Bull ; 37(10): 1493-1509, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34302618

RESUMO

The periaqueductal gray (PAG) is a complex mesencephalic structure involved in the integration and execution of active and passive self-protective behaviors against imminent threats, such as immobility or flight from a predator. PAG activity is also associated with the integration of responses against physical discomfort (e.g., anxiety, fear, pain, and disgust) which occurs prior an imminent attack, but also during withdrawal from drugs such as morphine and cocaine. The PAG sends and receives projections to and from other well-documented nuclei linked to the phenomenon of drug addiction including: (i) the ventral tegmental area; (ii) extended amygdala; (iii) medial prefrontal cortex; (iv) pontine nucleus; (v) bed nucleus of the stria terminalis; and (vi) hypothalamus. Preclinical models have suggested that the PAG contributes to the modulation of anxiety, fear, and nociception (all of which may produce physical discomfort) linked with chronic exposure to drugs of abuse. Withdrawal produced by the major pharmacological classes of drugs of abuse is mediated through actions that include participation of the PAG. In support of this, there is evidence of functional, pharmacological, molecular. And/or genetic alterations in the PAG during the impulsive/compulsive intake or withdrawal from a drug. Due to its small size, it is difficult to assess the anatomical participation of the PAG when using classical neuroimaging techniques, so its physiopathology in drug addiction has been underestimated and poorly documented. In this theoretical review, we discuss the involvement of the PAG in drug addiction mainly via its role as an integrator of responses to the physical discomfort associated with drug withdrawal.


Assuntos
Substância Cinzenta Periaquedutal , Transtornos Relacionados ao Uso de Substâncias , Tonsila do Cerebelo , Humanos , Morfina , Nociceptividade
15.
Molecules ; 26(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299631

RESUMO

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague-Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.


Assuntos
Analgésicos Opioides/farmacologia , Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Dor/tratamento farmacológico , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley
16.
Psychopharmacology (Berl) ; 238(10): 2895-2903, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34247265

RESUMO

RATIONALE: Social support and opioid replacement therapy are commonly used to treat opioid withdrawal. OBJECTIVE: The present study tested the hypothesis that social housing and buprenorphine administration can restore wheel running depressed by morphine withdrawal in rats. RESULTS: Experiment 1 assessed disruptive side effects of buprenorphine and found that administration of low doses (3.2, 10, & 32 µg/kg, s.c.) had no impact on voluntary wheel running. Experiment 2 assessed the impact of social housing and acute buprenorphine administration (10 µg/kg) on morphine withdrawal. Two 75 mg morphine pellets were implanted for 3 days to induce dependence. Removal of the morphine pellets caused a decrease in body weight, increase in wet dog shakes, and depression of wheel running during the normally active dark phase of the circadian cycle. Social housing restored wheel running and reduced the number of wet dog shakes but did not affect body weight. Administration of buprenorphine restored wheel running depressed by morphine withdrawal for 2 days in individually housed rats and produced time-dependent changes in socially housed rats: Depression of wheel running in the 3 h following administration and restoration of running subsequently compared to saline-treated controls. CONCLUSIONS: The impact of buprenorphine and social housing to reduce the effect of morphine withdrawal in rats is consistent with the use of opioid substitution therapy and psychotherapy/social support to treat opioid withdrawal in humans. These data provide further validation for the clinical relevance for the use of wheel running to assess spontaneous opioid withdrawal.


Assuntos
Buprenorfina , Atividade Motora , Síndrome de Abstinência a Substâncias , Animais , Habitação , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Entorpecentes/farmacologia , Ratos , Síndrome de Abstinência a Substâncias/tratamento farmacológico
17.
Bone Joint J ; 103-B(7 Supple B): 103-110, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34192916

RESUMO

AIMS: Due to the opioid epidemic in the USA, our service progressively decreased the number of opioid tablets prescribed at discharge after primary hip (THA) and knee (TKA) arthroplasty. The goal of this study was to analyze the effect on total morphine milligram equivalents (MMEs) prescribed and post-discharge opioid repeat prescriptions. METHODS: We retrospectively reviewed 19,428 patients undergoing a primary THA or TKA between 1 February 2016 and 31 December 2019. Two reductions in the number of opioid tablets prescribed at discharge were implemented over this time; as such, we analyzed three periods (P1, P2, and P3) with different routine discharge MME (750, 520, and 320 MMEs, respectively). We investigated 90-day refill rates, refill MMEs, and whether discharge MMEs were associated with represcribing in a multivariate model. RESULTS: A discharge prescription of < 400 MMEs was not a risk factor for opioid represcribing in the entire population (p = 0.772) or in opioid-naïve patients alone (p = 0.272). Procedure type was the most significant risk factor for narcotic represcribing, with unilateral TKA (hazard ratio (HR) = 5.62), bilateral TKA (HR = 6.32), and bilateral unicompartmental knee arthroplasty (UKA) (HR = 5.29) (all p < 0.001) being the highest risk for refills. For these three procedures, there was approximately a 5% to 6% increase in refills from P1 to P3 (p < 0.001); however, there was no significant increase in refill rates after any hip arthroplasty procedures. Total MMEs prescribed were significantly reduced from P1 to P3 (p < 0.001), leading to the equivalent of nearly 500,000 fewer oxycodone 5 mg tablets prescribed. CONCLUSION: Decreasing opioids prescribed at discharge led to a statistically significant reduction in total MMEs prescribed. While the represcribing rate did not increase for any hip arthroplasty procedure, the overall refill rates increased by about 5% for most knee arthroplasty procedures. As such, we are now probably prescribing an appropriate amount of opioids at discharge for knee arthroplasty procedure, but further reductions may be possible for hip arthroplasty procedures. Cite this article: Bone Joint J 2021;103-B(7 Supple B):103-110.


Assuntos
Analgésicos Opioides/administração & dosagem , Artroplastia de Quadril , Artroplastia do Joelho , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Alta do Paciente , Estudos Retrospectivos
18.
Clin J Pain ; 37(9): 664-668, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265791

RESUMO

CONTEXT AND OBJECTIVES: Although opioids play an indispensable role in the management of cancer-related pain, inadequate pain relief still occurs. The primary objective of this study was to evaluate whether the combination of a low dose of methadone with morphine promotes a reduction in opioid consumption; the secondary objectives were if the association promotes lower pain intensity, and adverse effects (AEs). MATERIALS AND METHODS: A sample if 41 patients with cancer-related pain in palliative setting were included. Patients were starting the third step of the analgesic ladder, and 1 group (n=21) achieve methadone (2.5 mg/12 h) in combination with morphine/methadone, and another group (n=20) received morphine alone. Both groups could use morphine (5 mg) as needed to maintain pain intensity <4, and adjuvant in stable dose. The following outcomes were evaluated: total morphine dose, pain intensity, and AEs. RESULTS: There was no difference in the number of adjuvants, and the dose of morphine used. Pain intensity was significantly lower in the morphine/methadone group after 2 weeks, with no statistically significant difference at other timepoints. There was no difference between groups in the AEs. CONCLUSION: Low dose of methadone in combination with morphine provided faster pain control as compared with morphine alone, and although this study was not powered to show differences in AEs, we did not notice a difference.


Assuntos
Dor do Câncer , Neoplasias , Analgésicos , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Humanos , Metadona/uso terapêutico , Morfina/uso terapêutico , Neoplasias/complicações
19.
Forensic Sci Int ; 325: 110893, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34273605

RESUMO

Toxicology investigation on human's buried dead bodies is a rare and challenging task in the forensic field. As requested by the Judicial Authority, this work aimed to verify testimonial evidence that emerged during a criminal investigation involving multiple murder cases. The statements indicated an improper medical administration of one or more alleged drugs (propofol, morphine, diazepam, and midazolam) which presumably caused the deaths. Since the supposed crimes took place several years before, the task of the present work was to obtain results to support the charges. The analyses involved 18 biological samples taken from four exhumed bodies, three of which were female and one male, each buried in a different date and mode. Each sample was treated with specific purification and extraction techniques (LLE - SPE) after the addition of the deuterated analogs of the searched analytes (propofol-d17, morphine-d3, diazepam-d5, midazolam-d4) as internal standards. Afterwards, the extracts were subjected to qualitative analysis by gas chromatography-mass spectrometry-Electron Impact (GC/MS - EI), both in full scan and SIM mode. Propofol, morphine, and diazepam were identified in the corpses. It supports testimonials that were administered just before the deaths occurred.


Assuntos
Diazepam/análise , Homicídio , Midazolam/análise , Morfina/análise , Propofol/análise , Idoso , Idoso de 80 Anos ou mais , Cadáver , Diazepam/envenenamento , Exumação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Rim/química , Fígado/química , Masculino , Midazolam/envenenamento , Morfina/envenenamento , Propofol/envenenamento , Bexiga Urinária/química
20.
J Opioid Manag ; 17(3): 251-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34259336

RESUMO

BACKGROUND: The management of post-operative pain and high levels of acute and chronic opioid use following total knee arthroplasty (TKA) and total hip arthroplasty (THA) remain challenges to the perioperative team. We performed a system-atic review and meta-analysis to determine the opioid sparing effects, analgesic effects, and safety profile of perioperative gabapentinoid usage in lower limb arthroplasty. METHODS: We searched multiple databases from inception until May 2019 and included randomized controlled trials (RCT) on perioperative gabapentinoids in lower limb arthroplasty. The primary outcome was cumulative opioid con-sumption (oral morphine equivalents) at 24 and 48 hours, and the secondary outcomes were pain scores, time to hospi-tal discharge, and adverse events including nausea, vomiting, pruritus, and sedation. Methodological quality was as-sessed using the Cochrane tool. The grading of recommendations assessment, development, and evaluation method-ology for the certainty of evidence was also used. RESULTS: We included 19 RCT involving 2,455 patients undergoing lower limb arthroplasty. The overall methodological quality of included studies was good. Gabapentinoid use was associated with a significant reduction in opioid consump-tion at 24 hour (mean difference (MD) 22.81 mg [95 percent Confidence Interval (CI) 13.64-31.98]) and 48 hour (MD 44.03 mg [95 percent CI 16.92-71.14]). We found no meaningful difference in pain scores at rest between gabapenti-noid and placebo groups at 24 or 48 hours. Gabapentinoid use reduced the risk of post-operative nausea (risk ratio (RR) 0.69 [95 percent CI 0.57-0.82]), vomiting (RR 0.65 [95 percent CI 0.47-0.91]), and pruritus (RR 0.60 [0.37-0.98]), but not sedation (RR 1.25 [0.76-2.06]). There was no effect on time to discharge from hospital (MD-0.05 days [95 per-cent CI -0.31 to 0.20]. CONCLUSIONS: The addition of gabapentinoids to perioperative multimodal analgesia decreases opioid consumption fol-lowing lower limb arthroplasty, while also lowering rates of nausea, vomiting, and pruritus. Further study is required to evaluate the effect of gabapentinoid use on long-term opioid use and dependence.


Assuntos
Analgésicos Opioides , Artroplastia do Joelho , Analgésicos Opioides/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Extremidade Inferior , Morfina , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...