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1.
Medicine (Baltimore) ; 99(5): e18502, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000360

RESUMO

BACKGROUND: Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients. METHODS: A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia. RESULTS: Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs. CONCLUSIONS: The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.


Assuntos
Unidades de Terapia Intensiva Pediátrica , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Criança , Humanos , Doença Iatrogênica , Síndrome de Abstinência a Substâncias/diagnóstico
2.
Expert Opin Drug Saf ; 19(2): 159-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876433

RESUMO

Introduction: Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD.Areas covered: Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA.Expert opinion: Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.


Assuntos
Alcoolismo/tratamento farmacológico , Oxibato de Sódio/administração & dosagem , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Oxibato de Sódio/efeitos adversos
3.
Cochrane Database Syst Rev ; 2019(11)2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31689723

RESUMO

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. Baclofen shows potential for rapidly reducing symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review first published in 2011 and last updated in 2017. OBJECTIVES: To assess the efficacy and safety of baclofen for people with AWS. SEARCH METHODS: We updated our searches of the following databases to June 2019: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. SELECTION CRITERIA: We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving. For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence). For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available. AUTHORS' CONCLUSIONS: No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence.


Assuntos
Baclofeno/uso terapêutico , Agonistas GABAérgicos/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Fissura , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Cochrane Database Syst Rev ; 9: CD013183, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31565800

RESUMO

BACKGROUND: The standard way most people are advised to stop smoking is by quitting abruptly on a designated quit day. However, many people who smoke have tried to quit many times and may like to try an alternative method. Reducing smoking behaviour before quitting could be an alternative approach to cessation. However, before this method can be recommended it is important to ensure that abrupt quitting is not more effective than reducing to quit, and to determine whether there are ways to optimise reduction methods to increase the chances of cessation. OBJECTIVES: To assess the effect of reduction-to-quit interventions on long-term smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, MEDLINE, Embase and PsycINFO for studies, using the terms: cold turkey, schedul*, cut* down, cut-down, gradual*, abrupt*, fading, reduc*, taper*, controlled smoking and smoking reduction. We also searched trial registries to identify unpublished studies. Date of the most recent search: 29 October 2018. SELECTION CRITERIA: Randomised controlled trials in which people who smoked were advised to reduce their smoking consumption before quitting smoking altogether in at least one trial arm. This advice could be delivered using self-help materials or behavioural support, and provided alongside smoking cessation pharmacotherapies or not. We excluded trials that did not assess cessation as an outcome, with follow-up of less than six months, where participants spontaneously reduced without being advised to do so, where the goal of reduction was not to quit altogether, or where participants were advised to switch to cigarettes with lower nicotine levels without reducing the amount of cigarettes smoked or the length of time spent smoking. We also excluded trials carried out in pregnant women. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Smoking cessation was measured after at least six months, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of comparison (no smoking cessation treatment, abrupt quitting interventions, and other reduction-to-quit interventions) and carried out meta-analyses where appropriate, using a Mantel-Haenszel random-effects model. We also extracted data on quit attempts, pre-quit smoking reduction, adverse events (AEs), serious adverse events (SAEs) and nicotine withdrawal symptoms, and meta-analysed these where sufficient data were available. MAIN RESULTS: We identified 51 trials with 22,509 participants. Most recruited adults from the community using media or local advertising. People enrolled in the studies typically smoked an average of 23 cigarettes a day. We judged 18 of the studies to be at high risk of bias, but restricting the analysis only to the five studies at low or to the 28 studies at unclear risk of bias did not significantly alter results.We identified very low-certainty evidence, limited by risk of bias, inconsistency and imprecision, comparing the effect of reduction-to-quit interventions with no treatment on cessation rates (RR 1.74, 95% CI 0.90 to 3.38; I2 = 45%; 6 studies, 1599 participants). However, when comparing reduction-to-quit interventions with abrupt quitting (standard care) we found evidence that neither approach resulted in superior quit rates (RR 1. 01, 95% CI 0.87 to 1.17; I2 = 29%; 22 studies, 9219 participants). We judged this estimate to be of moderate certainty, due to imprecision. Subgroup analysis provided some evidence (P = 0.01, I2 = 77%) that reduction-to-quit interventions may result in more favourable quit rates than abrupt quitting if varenicline is used as a reduction aid. Our analysis comparing reduction using pharmacotherapy with reduction alone found low-certainty evidence, limited by inconsistency and imprecision, that reduction aided by pharmacotherapy resulted in higher quit rates (RR 1. 68, 95% CI 1.09 to 2.58; I2 = 78%; 11 studies, 8636 participants). However, a significant subgroup analysis (P < 0.001, I2 = 80% for subgroup differences) suggests that this may only be true when fast-acting NRT or varenicline are used (both moderate-certainty evidence) and not when nicotine patch, combination NRT or bupropion are used as an aid (all low- or very low-quality evidence). More evidence is likely to change the interpretation of the latter effects.Although there was some evidence from within-study comparisons that behavioural support for reduction to quit resulted in higher quit rates than self-help resources alone, the relative efficacy of various other characteristics of reduction-to-quit interventions investigated through within- and between-study comparisons did not provide any evidence that they enhanced the success of reduction-to-quit interventions. Pre-quit AEs, SAEs and nicotine withdrawal symptoms were measured variably and infrequently across studies. There was some evidence that AEs occurred more frequently in studies that compared reduction using pharmacotherapy versus no pharmacotherapy; however, the AEs reported were mild and usual symptoms associated with NRT use. There was no clear evidence that the number of people reporting SAEs, or changes in withdrawal symptoms, differed between trial arms. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that neither reduction-to-quit nor abrupt quitting interventions result in superior long-term quit rates when compared with one another. Evidence comparing the efficacy of reduction-to-quit interventions with no treatment was inconclusive and of low certainty. There is also low-certainty evidence to suggest that reduction-to-quit interventions may be more effective when pharmacotherapy is used as an aid, particularly fast-acting NRT or varenicline (moderate-certainty evidence). Evidence for any adverse effects of reduction-to-quit interventions was sparse, but available data suggested no excess of pre-quit SAEs or withdrawal symptoms. We downgraded the evidence across comparisons due to risk of bias, inconsistency and imprecision. Future research should aim to match any additional components of multicomponent reduction-to-quit interventions across study arms, so that the effect of reduction can be isolated. In particular, well-conducted, adequately-powered studies should focus on investigating the most effective features of reduction-to-quit interventions to maximise cessation rates.


Assuntos
Abandono do Hábito de Fumar/métodos , Redução do Consumo de Tabaco , Síndrome de Abstinência a Substâncias/prevenção & controle , Bupropiona/uso terapêutico , Humanos , Nicotina/administração & dosagem , Agonistas Nicotínicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Abandono do Hábito de Fumar/psicologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Dispositivos para o Abandono do Uso de Tabaco
6.
Nutrients ; 11(8)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416242

RESUMO

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms, and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance, and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 polyunsaturated fatty acids (n-3 PUFAs), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that an n-3-PUFA-enriched diet ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and n-3 PUFA supplementation. We demonstrate that the withdrawal of opioids led to a significant depletion in specific microbiota genera, whereas n-3 PUFA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that n-3 PUFA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in n-3 PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.


Assuntos
Analgésicos Opioides , Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Comportamento de Procura de Droga/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Oxicodona , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/microbiologia , Transtornos Relacionados ao Uso de Opioides/psicologia , Recidiva , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/microbiologia , Síndrome de Abstinência a Substâncias/psicologia
7.
Trials ; 20(1): 468, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362784

RESUMO

BACKGROUND: The purpose of this study was to compare the effect of 300 mg of bupropion and 8 mg of buprenorphine per day on the treatment of methamphetamine withdrawal cravings over a 2-week treatment interval. METHOD: Sixty-five methamphetamine-dependent men who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria for methamphetamine dependence and withdrawal were randomly divided into two groups. Subjects randomly received 300 mg of bupropion or 8 mg of buprenorphine per day in a psychiatric ward. Of the 65 subjects, 35 (53.8%) received buprenorphine and 30 (46.2%) received bupropion. The subjects were assessed by using methamphetamine craving score, interview, and negative urine drug test. FINDINGS: There were no statistically significant differences between the two groups in regard to age, education, duration of methamphetamine dependency, marital status, employment, and income. The mean ages were 32.8 years (standard deviation (SD) = 7.26, range = 22 to 59) for the buprenorphine group and 32.21 years (SD = 8.45, range = 17 to 51) for the bupropion group. All 65 patients completed the 2-week study. Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group (P = 0.011). Overall, a significant main effect of day (P <0.001) and group (P = 0.011) and a non-significant group-by-day interaction (P >0.05) were detected. CONCLUSIONS: The results support the safety and effectiveness of buprenorphine and bupropion in the treatment of methamphetamine withdrawal craving. Administration of 8 mg of buprenorphine per day can be recommended for the treatment of methamphetamine withdrawal cravings. We should note that it is to be expected that craving decreases over time without any medication. So the conclusion may not be that bupropion and buprenorphine both lower the craving. As the buprenorphine is superior to bupropion, only buprenorphine does so for sure. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) registration number: IRCT2015010320540N1 . Date registered: April 10, 2015.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Comportamento Aditivo/tratamento farmacológico , Buprenorfina/uso terapêutico , Bupropiona/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Fissura/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Metanfetamina/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Analgésicos Opioides/efeitos adversos , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/psicologia , Buprenorfina/efeitos adversos , Bupropiona/efeitos adversos , Inibidores da Captação de Dopamina/efeitos adversos , Método Duplo-Cego , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Eur J Pharmacol ; 858: 172512, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31260653

RESUMO

The present study was conducted to evaluate the influence of AMN082, the metabotropic glutamate receptor subtype 7 (mGlu7) allosteric agonist on different stages of memory processes connected with fear conditioning in the passive avoidance (PA) learning task in mice and negative emotional state (anxiety-like) induced by ethanol- and morphine-withdrawal in the elevated plus maze (EPM) test in rats. To perform the PA test, AMN082 (1.25, 2.5 and 5 mg/kg, i. p.) was injected to interfere with (or inhibit) acquisition, consolidation, and retrieval processes. The retention latency in each group was recorded using a step-through passive avoidance task 24 h after training. In turn, in ethanol- and morphine-withdrawal rats, the influence of AMN082 on anxiety-like behavior was estimated in the EPM test 24 h- (ethanol) and 72- h (morphine) after the last dose of repeated drug administrations. In all experimental groups, AMN082 at the dose of 5 mg/kg significantly decreased the step-through latency of long-term memory in the PA task. These AMN082 effects were reversed by MMPIP (10 mg/kg), the antagonist of mGlu7 receptor. AMN082 (2.5 and 5 mg/kg) also decreased ethanol- and morphine withdrawal-induced anxiety-like behavior in the EPM test, and this AMN082 (5 mg/kg) effect was counteracted by MMPIP pretreatment. Taken together, the results show that mGlu7 is involved in fear learning to the context and anxiety-like state connected with unpleasant experiences after ethanol- and morphine withdrawal in rodents. However, it appears that functional dissociation exists between these two AMN082 effects.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Medo/efeitos dos fármacos , Medo/fisiologia , Memória/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/agonistas , Regulação Alostérica/efeitos dos fármacos , Animais , Ansiedade/fisiopatologia , Ansiedade/psicologia , Compostos Benzidrílicos/uso terapêutico , Relação Dose-Resposta a Droga , Masculino , Consolidação da Memória/efeitos dos fármacos , Camundongos , Ratos , Síndrome de Abstinência a Substâncias/tratamento farmacológico
9.
Molecules ; 24(14)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315244

RESUMO

Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders. In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed. CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- and stress-induced reinstatement of cocaine and priming-induced reinstatement of METH seeking behaviours. CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP and prevented priming-induced reinstatement of METH CPP. Observational studies suggest that CBD may reduce problems related with crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015). The potential mechanisms involved in the protective effects of CBD on addiction to psychostimulant drugs include the prevention of drug-induced neuroadaptations (neurotransmitter and intracellular signalling pathways changes), the erasure of aberrant drug-memories, the reversion of cognitive deficits induced by psychostimulant drugs and the alleviation of mental disorders comorbid with psychostimulant abuse. Further, preclinical studies and future clinical trials are necessary to fully evaluate the potential of CBD as an intervention for cocaine and methamphetamine addictive disorders.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Canabidiol/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Resiliência Psicológica , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Animais , Canabidiol/farmacologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Comportamentos de Risco à Saúde/efeitos dos fármacos , Humanos , Metanfetamina/toxicidade , Camundongos , Estudos Observacionais como Assunto , Síndrome de Abstinência a Substâncias/tratamento farmacológico
10.
Rev Med Liege ; 74(5-6): 365-372, 2019 05.
Artigo em Francês | MEDLINE | ID: mdl-31206282

RESUMO

Acute alcohol withdrawal is a frequent medical condition among hospitalized patients. Severe forms are associated with significant morbidity and mortality, which can be sharply reduced with proper drug therapy. A good understanding of the pathophysiology as well as the pharmacokinetic and pharmacodynamic properties of the various drug used is paramount. The medications must target the imbalance between inhibitory and excitatory neurotransmitter systems responsible for the clinical picture. Proper drug therapy allows not only rapid symptomatic relief but also limit disease progression and complications while diminishing resource use, notably invasive ventilation and stay duration in the intensive care unit. GABA agonist drugs are the first line treatment, notably benzodiazepines and barbiturates. Other class, such as alpha-2 adrenoreceptor agonists may be used to control the dysautonomic features of the disease but are at best adjunctive.


Assuntos
Delirium por Abstinência Alcoólica , Alcoolismo , Síndrome de Abstinência a Substâncias , Delirium por Abstinência Alcoólica/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Síndrome de Abstinência a Substâncias/tratamento farmacológico
12.
Pharmacol Biochem Behav ; 181: 86-92, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082417

RESUMO

BACKGROUND: As long-term use of medicinal and recreational cannabis becomes more common and concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis increase, it is timely to identify strategies to counteract the cognitive effects of cannabinoids. OBJECTIVE: Galantamine is an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease and other dementias. This study aimed to investigate the feasibility of galantamine administration to individuals with cannabis use disorder (CUD), and the effects of galantamine on cognition. We hypothesized galantamine would be well tolerated and would not have procognitive effects in the absence of acute cannabis intoxication. METHODS: Thirty individuals with CUD (73.5% male, 26.5% female) participated in a randomized, double-blind, parallel-group trial. Participants completed a baseline session followed by a 10-day outpatient treatment period, during which they received either 8 mg/day of galantamine orally or placebo. Cognitive assessments were conducted at three time points and self-reported measures that may impact cognitive performance (cannabis withdrawal, craving, and mood) were completed at six time points. RESULTS: There were no significant differences in demographic and baseline variables between groups (galantamine vs. placebo). There were no significant adverse effects from galantamine. Cannabis withdrawal and craving continuously decreased over the study. We saw evidence of a modest improvement in cognitive outcomes during the 10-day period, exemplified by a statistically significant increase in measures of response inhibition (increased median reaction time on the Stop Signal Task), and a trend for improvement in measures of attention (increased RVP A'), for both groups. Analyses did not show, however, a significant main effect for treatment or treatment-by-time interactions. CONCLUSIONS: The findings of this pilot study support the feasibility of the administration of galantamine for individuals with CUD. Adequately powered, randomized, placebo-controlled trials are required to investigate the potential of galantamine to improve cognitive deficits associated with CUD.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Cognição/efeitos dos fármacos , Galantamina/uso terapêutico , Abuso de Maconha/tratamento farmacológico , Adolescente , Adulto , Afeto/efeitos dos fármacos , Atenção/efeitos dos fármacos , Inibidores da Colinesterase/administração & dosagem , Fissura/efeitos dos fármacos , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Galantamina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tempo de Reação/efeitos dos fármacos , Autorrelato , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto Jovem
14.
Psychopharmacology (Berl) ; 236(11): 3095-3110, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31073738

RESUMO

RATIONALE: Sugar has addictive potential owing to increase in monoaminergic-transmission at pleasure and reward centers of brain. Insulin dysfunction triggered synaptic monoamine deficit is associated with sugar overeating and craving-related psychological changes in diabetic patients. Sugar-substitute (saccharin) is non-caloric artificial sweetener that may alleviate brain disorders in diabetes. OBJECTIVES: In present study, effects of sucrose and sugar-substitute (saccharin) exposures and withdrawal on depression and anxiety-like behavior in type 2 diabetic mice were assessed. METHODS: Swiss albino mice were injected with streptozotocin (135 mg/kg). After induction of diabetes, mice were exposed to a two-bottle water-water, 10% sucrose-water, or 10% saccharin-water choice paradigm for 28 days. Separate groups were employed to assess withdrawal effect of sucrose or saccharin in diabetic mice. Monoamine oxidase (MAO), corticosterone, thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) were quantified after behavioral tests. RESULTS: Diabetic mice manifested preference towards 10% sucrose or saccharin over water. Sucrose-overeating by diabetic mice amplified symptoms of depression and anxiety; however, withdrawal further exaggerated these behavioral abnormalities. Substitution of sucrose by 10% saccharin attenuated the depressive and anxiety-like behavior in comparison to diabetic mice that were exposed separately to water-water or sucrose-water alone, and with respect to normal mice. Although withdrawal from saccharin resurfaced behavioral anomalies in diabetic mice, however, these were significantly low in comparison with withdrawal from sucrose or normal group. Reinstatement of exposure to saccharin mitigated symptoms of depression and anxiety in diabetic mice. CONCLUSION: Preference of sucrose overeating augments while saccharin mitigates depressive and anxiety behavior during diabetes.


Assuntos
Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Sacarina/administração & dosagem , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Sacarose/administração & dosagem , Animais , Ansiedade/psicologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Depressão/psicologia , Diabetes Mellitus Experimental/psicologia , Feminino , Masculino , Camundongos , Recompensa , Síndrome de Abstinência a Substâncias/psicologia
15.
Bull Exp Biol Med ; 166(6): 739-743, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020587

RESUMO

Activities of noncompetitive NMDA receptor antagonists (aminoadamantane derivatives) were assessed in random-bred rats with modeled morphine withdrawal syndrome. A single intraperitoneal injection of hemantane (10 or 20 mg/kg) significantly and dose-dependently moderated some behavioral symptoms (teeth-chattering, ptosis, and vocalization) and reduced total score of morphine withdrawal syndrome. In morphine-abstinent rats, hemantane partially prevented the decrease in the thresholds of tactile sensitivity, but had no effect on locomotor activity and body weight loss. Under conditions of morphine withdrawal, intraperitoneal injection of amantadine (10 or 20 mg/kg) decreased motor activity and promoted body weight loss in parallel with the development of mechanical allodynia, but had no effect on the total withdrawal score. Comparison of aminoadamantane derivatives by behavioral and physiological parameters demonstrated the advantage of hemantane during morphine abstinence indicating the need of its study as a promising anti-addiction remedy.


Assuntos
Adamantano/análogos & derivados , Amantadina/farmacologia , Dependência de Morfina/fisiopatologia , Antagonistas de Entorpecentes/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adamantano/farmacologia , Animais , Expressão Gênica , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Injeções Intraperitoneais , Masculino , Morfina/administração & dosagem , Dependência de Morfina/genética , Dependência de Morfina/metabolismo , Atividade Motora/efeitos dos fármacos , Ratos , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/fisiopatologia , Perda de Peso/efeitos dos fármacos
16.
Pharmacol Biochem Behav ; 181: 9-16, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954637

RESUMO

Learning processes associated with nicotine influence the development of addiction to tobacco products. In the present report, we are interested in the interoceptive stimulus effects of nicotine acquiring control over appetitive behaviors - specifically, reward seeking. Also of interest is the current smoking cessation drug, varenicline (Chantix®). Varenicline, with its nicotine-like stimulus effects, can decrease withdrawal and cravings for a subset of individuals addicted to nicotine, though relapse is still common. We trained rats (N = 48) with nicotine (0.4 mg/kg, SC) as an excitatory stimulus (i.e., paired with sucrose) in a drug-discriminated goal-tracking (DGT) task. There was no access to sucrose on interspersed saline days. After acquisition of the initial nicotine-saline discrimination, rats were separated into four groups to test discrimination reversal and drug substitution. The control group maintained nicotine as the excitatory stimulus (NIC+). The substitution group had varenicline (1 mg/kg) replace nicotine as the stimulus paired with sucrose (VAR+). One reversal group had nicotine signal the absence of sucrose (i.e., now available on intermixed saline sessions; NIC-). The last group was similar to the NIC- group except varenicline replaced nicotine on non-reinforced sessions (VAR-). We found that varenicline fully substituted as the training stimulus when the drug-sucrose relation remained in place (VAR+). Both reversal groups acquired the new discrimination, albeit slowly and more variable for the VAR- group in comparison to NIC-. There was an effect of group during substitution testing. Specifically, nicotine fully substituted for varenicline regardless of condition. However, varenicline only partially substituted for the nicotine stimulus. At the start of extinction, responding mimicked that of the rats training condition. However, by extinction session 12, all groups maintained similarly low levels of responding. These findings show nicotine and varenicline share stimulus elements, yet the conclusion of partial to full substitution depends on the nature of the testing protocol.


Assuntos
Comportamento Apetitivo/efeitos dos fármacos , Interocepção/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Vareniclina/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Substituição de Medicamentos , Extinção Psicológica/efeitos dos fármacos , Injeções Subcutâneas , Masculino , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solução Salina/farmacologia , Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Sacarose/farmacologia , Vareniclina/administração & dosagem
17.
Fortschr Neurol Psychiatr ; 87(4): 259-270, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30999380

RESUMO

Long-term prescriptions of benzodiazepines are made mainly to elderly and female patients. Withdrawal treatments should be carried out gradually over a period of several weeks. Sleep and depressive disorders during benzodiazepine withdrawal can best be treated with sedating antidepressants. The few studies on this subject suggest psychoeducation, motivational strategies and cognitive behavioural therapy as having some efficacy.


Assuntos
Ansiolíticos , Antidepressivos/uso terapêutico , Benzodiazepinas , Terapia Cognitivo-Comportamental , Hipnóticos e Sedativos/uso terapêutico , Síndrome de Abstinência a Substâncias/terapia , Ansiolíticos/administração & dosagem , Ansiolíticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Humanos , Motivação , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/psicologia
18.
Psychopharmacology (Berl) ; 236(9): 2623-2633, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30993360

RESUMO

RATIONALE: Oleoyl glycine (OlGly), a recently discovered fatty acid amide that is structurally similar to N- acylethanolamines, which include the endocannabinoid, anandamide (AEA), as well as endogenous peroxisome proliferator-activated receptor alpha (PPARα) agonists oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), has been shown to interfere with nicotine reward and dependence in mice. OBJECTIVES AND METHODS: Behavioral and molecular techniques were used to investigate the ability of OlGly to interfere with the affective properties of morphine and morphine withdrawal (MWD) in male Sprague-Dawley rats. RESULTS: Synthetic OlGly (1-30 mg/kg, intraperitoneal [ip]) produced neither a place preference nor aversion on its own; however, at doses of 1 and 5 mg/kg, ip, it blocked the aversive effects of MWD in a place aversion paradigm. This effect was reversed by the cannabinoid 1 (CB1) receptor antagonist, AM251 (1 mg/kg, ip), but not the PPARα antagonist, MK886 (1 mg/kg, ip). OlGly (5 or 30 mg/kg, ip) did not interfere with a morphine-induced place preference or reinstatement of a previously extinguished morphine-induced place preference. Ex vivo analysis of tissue (nucleus accumbens, amygdala, prefrontal cortex, and interoceptive insular cortex) collected from rats experiencing naloxone-precipitated MWD revealed that OlGly was selectively elevated in the nucleus accumbens. MWD did not modify levels of the endocannabinoids 2-AG and AEA, nor those of the PPARα ligands, OEA and PEA, in any region evaluated. CONCLUSION: Here, we show that OlGly interferes with the aversive properties of acute naloxone-precipitated morphine withdrawal in rats. These results suggest that OlGly may reduce the impact of MWD and may possess efficacy in treating opiate withdrawal.


Assuntos
Analgésicos Opioides/efeitos adversos , Glicina/análogos & derivados , Morfina/efeitos adversos , Naloxona/toxicidade , Ácidos Oleicos/administração & dosagem , Recompensa , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Relação Dose-Resposta a Droga , Glicina/administração & dosagem , Glicina/metabolismo , Masculino , Camundongos , Antagonistas de Entorpecentes/toxicidade , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ácidos Oleicos/metabolismo , Ratos , Ratos Sprague-Dawley , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologia
20.
Pharm Biol ; 57(1): 145-153, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30922154

RESUMO

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.


Assuntos
Intoxicação Alcoólica/tratamento farmacológico , Phyllanthus , Fitoterapia/métodos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Intoxicação Alcoólica/sangue , Biomarcadores/sangue , Estudos Cross-Over , Citocinas/sangue , Suplementos Nutricionais , Método Duplo-Cego , Etanol/sangue , Feminino , Cefaleia/sangue , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Extratos Vegetais/farmacologia , Folhas de Planta , Síndrome de Abstinência a Substâncias/etiologia
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