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2.
Handb Exp Pharmacol ; 258: 299-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32193666

RESUMO

In recent years, use of cocaine and amphetamines and deaths associated with stimulants have been on the rise, and there are still no FDA-approved medications for stimulant use disorders. One contributing factor may involve heterogeneity. At the neurobiological level, dual dopamine dysfunction may be undermining medication efficacy, suggesting a need for combination pharmacotherapies. At the population level, individual variability is expressed in a number of ways and, if left unaddressed, may interfere with medication efficacy. This chapter reviews studies investigating medications to address dopamine dysfunction, and it also identifies several prominent heterogeneities associated with stimulant (and other substance) use disorders. The chapter has implications for improving interventions to treat stimulant use disorders, and the theme of individual heterogeneity may have broader application across substance use disorders.


Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Dopamina/fisiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Anfetaminas/efeitos adversos , Ensaios Clínicos como Assunto , Cocaína , Transtornos Relacionados ao Uso de Cocaína , Humanos
3.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
5.
Drug Alcohol Depend ; 206: 107700, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753736

RESUMO

BACKGROUND: Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users. METHODS: A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report. RESULTS: The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%). CONCLUSIONS: While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."


Assuntos
Anfetaminas/uso terapêutico , Topiramato/uso terapêutico , Anfetaminas/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/terapia , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Sais/uso terapêutico , Topiramato/efeitos adversos , Resultado do Tratamento
6.
Lancet ; 394(10209): 1652-1667, 2019 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668409

RESUMO

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.


Assuntos
Anfetaminas/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/mortalidade , Cocaína/efeitos adversos , Adolescente , Adulto , Anfetaminas/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/prevenção & controle , Inibidores da Captação de Dopamina/efeitos adversos , Feminino , Infecções por HIV/induzido quimicamente , Infecções por HIV/mortalidade , Hepatite C/induzido quimicamente , Hepatite C/mortalidade , Humanos , Incidência , Masculino , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/mortalidade , Pessoa de Meia-Idade , Prevalência , Viroses/sangue , Viroses/induzido quimicamente , Viroses/mortalidade , Adulto Jovem
7.
Pharmacotherapy ; 39(12): 1167-1178, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31674031

RESUMO

OBJECTIVE: To examine whether concomitant use of quinolones and stimulants increases the risk of cardiac events in adults. STUDY DESIGN: A retrospective cohort study of privately insured adults using MarketScan® claims data from 2008 to 2015. PATIENTS: Stimulant (methylphenidate or mixed amphetamine salts) users (18-65 yrs old) with continuous health plan enrollment for the 6 months (baseline) prior to the first dispensation (index date) of oral quinolones or comparators (amoxicillin ± clavulanate or azithromycin). OUTCOMES DEFINITION: (1) Cardiac symptoms (palpitation, tachycardia, or syncope); (2) cardiac arrhythmias (ventricular arrhythmias, paroxysmal ventricular tachycardia, or cardiac arrest). ANALYSIS: Baseline covariates adjustment was through inverse probability of treatment weighting. Adults were followed until the antimicrobial therapy ended. The hazard of cardiac events in stimulant-quinolones-exposed adults was compared to those who were treated with stimulant-comparator antibiotics using a weighted Cox regression model. Several sensitivity analyses were performed to challenge the results robustness. RESULTS: The study cohorts comprised 390,490 stimulants users who initiated either quinolone or amoxicillin, and 387,574 patients receiving stimulants who initiated quinolone or azithromycin. The unadjusted incidence rate for cardiac symptoms in stimulant-quinolones users was 471 cases/10,000 patient-years, and it was 244 cases/10,000 patient-years in patients exposed to stimulant-amoxicillin; whereas the unadjusted incidence rate for cardiac symptoms was 728 and 358 per 10,000 patient-years for stimulant-quinolones and stimulant-azithromycin cohorts, respectively. Compared to stimulant-amoxicillin use, the adjusted hazard ratio (HR) for cardiac symptoms with stimulant-quinolones use was 1.61 (95% confidence interval [CI], 1.30-1.98). The HR for cardiac symptoms for patient exposed to stimulant-quinolones was 1.69 (95% CI, 1.32-2.13) when compared to stimulant-azithromycin. The sensitivity analysis findings were consistent with the primary analysis. A few patients across the study comparison groups developed cardiac arrhythmias. CONCLUSION: Concomitant use of stimulants and quinolone was associated with an increased hazard of cardiac symptoms in comparison to concomitant use of stimulants and amoxicillin or azithromycin, but there was no apparent difference in cardiac arrhythmias.


Assuntos
Antibacterianos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Quinolonas/efeitos adversos , Adolescente , Adulto , Idoso , Anfetaminas/administração & dosagem , Anfetaminas/efeitos adversos , Antibacterianos/administração & dosagem , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estudos de Coortes , Interações Medicamentosas , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Quinolonas/administração & dosagem , Estudos Retrospectivos , Adulto Jovem
8.
Praxis (Bern 1994) ; 108(13): 869-876, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31571536

RESUMO

Knockout Drugs: Diagnostics in the Emergency Unit and Clinical Practice Abstract. Every now and then, physicians are challenged with date rape drugs. If there is a suspicion of substance administration, the question of involving forensic medicine is commonly raised. In obscure situations or questionable offences, however, patients may wish for an initial diagnosis in the emergency department or the private practice. The physicians are often greatly challenged by the variety of substances, the limited analytical methods and difficulties with the interpretion of results. The major goal of this article is to present diagnostic options including their limitations. An overview of frequently involved substances is provided. Particular focus will be placed on practical aspects, including questions regarding pre-analytics and health insurance coverage.


Assuntos
Preparações Farmacêuticas , Médicos , Detecção do Abuso de Substâncias , Anfetaminas/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Serviço Hospitalar de Emergência , Humanos , Estupro
9.
Can J Surg ; 62(5): 356-357, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550103

RESUMO

Summary: Cardiac toxicity from recreational drug use remains difficult to establish. We report the cases of 3 young patients who were hospitalized for cardiogenic shock. All were bridged to transplantation with implantation of a left ventricular assist device (LVAD). They underwent uneventful heart transplantation. The patients did not have any significant personal or family medical history, but all admitted consuming large quantities of recreational drugs daily. Histological examination of the native heart did not show any inflammation or infiltrative myocardial disease. In this series of young patients presenting in cardiogenic shock with minimal histologic findings on examination of the native hearts, the association between cardiac toxicity and active use of recreational drugs remains a strong possibility. The transplant community should be made aware of this possible association in the current era of legalization and social trivialization of drug consumption.


Assuntos
Cardiomiopatia Dilatada/etiologia , Cardiotoxicidade/etiologia , Transplante de Coração , Drogas Ilícitas/efeitos adversos , Choque Cardiogênico/etiologia , Adulto , Anfetaminas/efeitos adversos , Cannabis/efeitos adversos , Cardiomiopatia Dilatada/cirurgia , Cardiotoxicidade/cirurgia , Cocaína/efeitos adversos , Coração Auxiliar , Humanos , Choque Cardiogênico/cirurgia , Resultado do Tratamento , Adulto Jovem
10.
Med Hypotheses ; 132: 109327, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421431

RESUMO

Dementia is a cluster of brain dysfunctions with a characteristic of progressively debilitating in individuals' ability of operating cognitive functions and that affects seriously to patients' daily life. We presented a hypothesis in this article that earlier exposure of a common used cognitive enhancer amphetamine may lead to individuals to be more liable to develop dementia in their later life based on the opponent process theory. The theory proposes that following a positive response, homeostatic changes in brain circuits may function to go opposite to the positive response, thus a cognitive deterioration may incur in later life in the individuals who exposed to amphetamine earlier. Along with the hypothesis, amphetamine is also highly associated with the working hypothesis updated for dementia in terms of beta-amyloid cascade, tau protein, oxidative stress and neural inflammation. Finally, we presented two practical methods to evaluate the hypothesis. In non-human approach, rat model of amphetamine dependence would be employed together with evaluations of behavioral performance of memory test and neurochemical markers associated with oxidative stress. In human approach, a matched-cohort design observational study would be highly recommended.


Assuntos
Anfetaminas/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Demência/etiologia , Demência/fisiopatologia , Transtornos Relacionados ao Uso de Anfetaminas , Peptídeos beta-Amiloides/metabolismo , Animais , Comportamento Animal , Modelos Animais de Doenças , Homeostase , Memória/efeitos dos fármacos , Estresse Oxidativo , Ratos , Transtornos Relacionados ao Uso de Substâncias , Proteínas tau/metabolismo
11.
Medicina (Kaunas) ; 55(7)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330913

RESUMO

Background and Objectives: Previously we have shown that synthetic lunasin, a 43 amino acid residue-containing peptide, after its central (intracisternal) administration in mice demonstrated antagonism against dopaminergic drug behavioural effects, indicating a putative antipsychotic/anti-schizophrenic profile of lunasin. The aims of the present studies were: to test whether lunasin would show an influence on the dopaminergic system after intranasal administration, and to examine the effect(s) of lunasin on serotonin and glutamatergic systems, which could play an essential role in antipsychotic action. Materials and Methods: Lunasin was administered intra-nasally at doses 0.1 and 1 nmol/mouse in ICR mice (n = 7-8) and tested in an open field on hyperlocomotion caused by amphetamine; serotonin 5-HT 2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane (DOI); and glutamate NMDA receptor antagonist phencyclidine. Following behavioural testing, the contents of neurotransmitters and their metabolites in brain hemispheres (n = 6-8) were assessed by ultra-high-performance liquid chromatography-time of flight mas-spectrometry (UHPLC-TOF-MS) method. Also, lunasin binding to serotonin receptors was assessed. Results: Lunasin intra-nasally fully normalized hyper-locomotion and brain monoamine levels in amphetamine- and DOI-treated mice brains. Phencyclidine behavioural effects were not influenced. In vitro receptor binding data demonstrated a low affinity of lunasin (at µM concentrations) compared with DOI (nM concentrations) for the 5-HT2A and 5-HT2C receptors. Conclusions: These results demonstrated, for the first time, that the intranasal administration of oligopeptide lunasin normalized mice behaviour and brain monoamine levels in experimental psychosis mice models. Its neuro-regulatory effects indicated a usefulness of this peptide molecule for the design of novel psychotropic agents.


Assuntos
Antipsicóticos/análise , Oligopeptídeos/uso terapêutico , Administração Intranasal , Anfetaminas/administração & dosagem , Anfetaminas/efeitos adversos , Anfetaminas/uso terapêutico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos ICR/metabolismo , Atividade Motora/efeitos dos fármacos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia
12.
J Pharmacol Exp Ther ; 369(3): 328-336, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30898867

RESUMO

ß-Methylphenethylamine [(BMPEA), 2-phenylpropan-1-amine] is a structural isomer of amphetamine (1-phenylpropan-2-amine) that has been identified in preworkout and weight loss supplements, yet little information is available about its pharmacology. Here, the neurochemical and cardiovascular effects of BMPEA and its analogs, N-methyl-2-phenylpropan-1-amine (MPPA) and N,N-dimethyl-2-phenylpropan-1-amine (DMPPA), were compared with structurally related amphetamines. As expected, amphetamine and methamphetamine were potent substrate-type releasing agents at dopamine transporters (DATs) and norepinephrine transporters (NETs) in rat brain synaptosomes. BMPEA and MPPA were also substrates at DATs and NETs, but they were at least 10-fold less potent than amphetamine. DMPPA was a weak substrate only at NETs. Importantly, the releasing actions of BMPEA and MPPA were more potent at NETs than DATs. Amphetamine produced significant dose-related increases in blood pressure (BP), heart rate (HR), and locomotor activity in conscious rats fitted with surgically implanted biotelemetry transmitters. BMPEA, MPPA, and DMPPA produced increases in BP that were similar to the effects of amphetamine, but the compounds failed to substantially affect HR or activity. The hypertensive effect of BMPEA was reversed by the α-adrenergic antagonist prazosin but not the ganglionic blocker chlorisondamine. Radioligand binding at various G protein-coupled receptors did not identify nontransporter sites of action that could account for cardiovascular effects of BMPEA or its analogs. Our results show that BMPEA, MPPA, and DMPPA are biologically active. The compounds are unlikely to be abused due to weak effects at DATs, but they could produce adverse cardiovascular effects via substrate activity at peripheral NET sites.


Assuntos
Anfetaminas/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Animais , Frequência Cardíaca/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Temperatura
13.
Neurocrit Care ; 31(2): 288-296, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30788708

RESUMO

BACKGROUND: Abnormal restricted diffusion on magnetic resonance imaging is often associated with ischemic stroke or anoxic injury, but other conditions can present similarly. We present six cases of an unusual but consistent pattern of restricted diffusion in bilateral hippocampi and cerebellar cortices. This pattern of injury is distinct from typical imaging findings in ischemic, anoxic, or toxic injury, suggesting it may represent an under-recognized clinicoradiographic syndrome. Despite initial presentation with stupor or coma in the context of obstructive hydrocephalus, patients may have acceptable outcomes if offered early intervention. METHODS: We identified an ad hoc series of patients at our two institutions between years 2014 and 2017 who presented to the neurocritical care unit with severe, otherwise unexplained cerebellar edema and retrospectively identified several commonalities in history, presentation, and imaging. RESULTS: Between two institutions, we identified six patients-ages 33-59 years, four male-with similar presentations of decreased level of consciousness in the context of intoxicant exposure, with acute cytotoxic edema of the cerebellar cortex, hippocampi, and aspects of the basal nuclei. All patients presented with severe cerebellar edema which led to obstructive hydrocephalus requiring aggressive medical and/or surgical management. The five patients who survived to discharge demonstrated variable degrees of physical and memory impairment on discharge and at follow-up. CONCLUSIONS: We present findings of a potentially novel syndrome involving a distinct pattern of cerebellar and hippocampal restricted diffusion, with imaging and clinical characteristics distinct from ischemic stroke, hypoxic injury, and known toxidromes and leukoencephalopathies. Given the potential for favorable outcome despite early obstructive hydrocephalus, early identification and treatment of this syndrome are critical.


Assuntos
Gânglios da Base/diagnóstico por imagem , Benzodiazepinas/efeitos adversos , Edema Encefálico/diagnóstico por imagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Córtex Cerebelar/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Hidrocefalia/diagnóstico por imagem , Alcaloides Opiáceos/efeitos adversos , Adulto , Intoxicação Alcoólica/complicações , Anfetaminas/efeitos adversos , Edema Encefálico/induzido quimicamente , Edema Encefálico/fisiopatologia , Edema Encefálico/terapia , Cerebelo/diagnóstico por imagem , Cocaína/efeitos adversos , Coma/etiologia , Feminino , Heroína/efeitos adversos , Humanos , Hidrocefalia/etiologia , Hidrocefalia/fisiopatologia , Hidrocefalia/terapia , Hidromorfona/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Estupor/etiologia , Transtornos Relacionados ao Uso de Substâncias , Síndrome
14.
Psychopharmacology (Berl) ; 236(3): 881-890, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30069588

RESUMO

RATIONALE: The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold. OBJECTIVES: To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics. RESULTS: In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar Tmax and t1/2 in male rats. MDPV, a structurally distinct synthetic cathinone from mephedrone and methylone, has a lower Tmax and t1/2. Increasing the length of the alkyl chain on the α position of methylone, to produce pentylone, results in increased plasma concentrations and longer t1/2. Metabolism of the synthetic cathinones is reasonably predictable based on the chemical structure, and several phase I metabolites retain pharmacodynamic activity. CYP2D6 is implicated in the metabolism of all of the synthetic cathinones, and other P450s (CYP1A2, CYP2B6, and CYP2C19) are known to contribute variably to the metabolism of specific synthetic cathinones. CONCLUSIONS: Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.


Assuntos
Alcaloides/química , Alcaloides/farmacocinética , Medicamentos Sintéticos/química , Medicamentos Sintéticos/farmacocinética , Alcaloides/efeitos adversos , Anfetaminas/efeitos adversos , Anfetaminas/química , Anfetaminas/farmacocinética , Animais , Drogas Desenhadas/efeitos adversos , Drogas Desenhadas/química , Drogas Desenhadas/farmacocinética , Humanos , Metanfetamina/efeitos adversos , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/farmacocinética , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Medicamentos Sintéticos/efeitos adversos
16.
CNS Spectr ; 24(5): 479-495, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30460884

RESUMO

OBJECTIVE: Our aim was to summarize the efficacy and safety of atomoxetine, amphetamines, and methylphenidate in schizophrenia. METHODS: We undertook a systematic review, searching PubMed/Scopus/Clinicaltrials.gov for double-blind, randomized, placebo-controlled studies of psychostimulants or atomoxetine in schizophrenia published up to 1 January 2017. A meta-analysis of outcomes reported in two or more studies is presented. RESULTS: We included 22 studies investigating therapeutic effects of stimulants (k=14) or measuring symptomatic worsening/relapse prediction after stimulant challenge (k=6). Six studies of these two groups plus one additional study investigated biological effects of psychostimulants or atomoxetine. No effect resulted from interventional studies on weight loss (k=1), smoking cessation (k=1), and positive symptoms (k=12), and no improvement was reported with atomoxetine (k=3) for negative symptoms, with equivocal findings for negative (k=6) and mood symptoms (k=2) with amphetamines. Attention, processing speed, working memory, problem solving, and executive functions, among others, showed from no to some improvement with atomoxetine (k=3) or amphetamines (k=6). Meta-analysis did not confirm any effect of stimulants in any symptom domain, including negative symptoms, apart from atomoxetine improving problem solving (k=2, standardized mean difference (SMD)=0.73, 95% CI=0.10-1.36, p=0.02, I2=0%), and trending toward significant improvement in executive functions with amphetamines (k=2, SMD=0.80, 95% CI=-1.68 to +0.08, p=0.08, I2=66%). In challenge studies, amphetamines (k=1) did not worsen symptoms, and methylphenidate (k=5) consistently worsened or predicted relapse. Biological effects of atomoxetine (k=1) and amphetamines (k=1) were cortical activation, without change in ß-endorphin (k=1), improved response to antipsychotics after amphetamine challenge (k=2), and an increase of growth hormone-mediated psychosis with methylphenidate (k=2). No major side effects were reported (k=6). CONCLUSIONS: No efficacy for stimulants or atomoxetine on negative symptoms is proven. Atomoxetine or amphetamines may improve cognitive symptoms, while methylphenidate should be avoided in patients with schizophrenia. Insufficient evidence is available to draw firm conclusions.


Assuntos
Antipsicóticos/efeitos adversos , Cloridrato de Atomoxetina/efeitos adversos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Anfetaminas/administração & dosagem , Anfetaminas/efeitos adversos , Anfetaminas/uso terapêutico , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Cloridrato de Atomoxetina/administração & dosagem , Cloridrato de Atomoxetina/uso terapêutico , Atenção , Função Executiva , Humanos , Memória de Curto Prazo , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Metilfenidato/uso terapêutico , Resolução de Problemas
17.
Vasc Med ; 24(1): 50-55, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30105937

RESUMO

Amphetamine and its related derivatives and analogues (ADRA) are highly addictive central nervous system stimulants that are used commonly in the treatment of attention-deficit/hyperactivity disorder and narcolepsy. These medications are associated with many side effects but reports of peripheral arterial manifestations associated with ADRA usage are scarce. We retrospectively reviewed the records of 16 patients (median age 37 years (IQR 31-47), 13 females) referred to a single tertiary referral service while receiving ADRA. Follow-up was available for a median of 3 years (IQR 3-4.5). The most common presentation (62.5%) was mild vasospastic symptoms involving the upper, lower or both extremities. Six patients developed severe manifestations including tissue loss and the need for lower extremity amputation. Most patients (75%) refused to stop the medication during follow-up. Underlying rheumatologic disorders were found in 25% of the patients, and the presence of rheumatologic disease seemed to be associated with more severe vascular manifestations. In conclusion, it is important to search for ADRA usage as part of the differential diagnosis of digital ischemia.


Assuntos
Anfetaminas/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Isquemia/induzido quimicamente , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/induzido quimicamente , Extremidade Superior/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Adulto , Amputação , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Isquemia/terapia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
18.
Cochrane Database Syst Rev ; 12: CD011315, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577083

RESUMO

BACKGROUND: Amphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related substances. ATS are highly addictive and prolonged use may result in a series of mental and physical symptoms including anxiety, confusion, insomnia, mood disturbances, cognitive impairments, paranoia, hallucinations and delusion.Currently there is no widely accepted treatment for ATS-use disorder. However, cognitive-behavioural treatment (CBT) is the first-choice treatment. The effectiveness of CBT for other substance-use disorders (e.g. alcohol-, opioid- and cocaine-use disorders) has been well documented and as such this basic treatment approach has been applied to the ATS-use disorder. OBJECTIVES: To investigate the efficacy of cognitive-behavioural treatment for people with ATS-use disorder for reducing ATS use compared to other types of psychotherapy, pharmacotherapy, 12-step facilitation, no intervention or treatment as usual. SEARCH METHODS: We identified randomised controlled trials (RCT) and quasi-RCTs comparing CBT for ATS-use disorders with other types of psychotherapy, pharmacotherapy, 12 step facilitation or no intervention. We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Embase and five other databases up to July 2018. In addition, we examined reference lists of eligible studies and other systematic reviews. We contacted experts in the field. SELECTION CRITERIA: Eligibility criteria consisted of RCTs and quasi-RCTs comparing CBT versus other types of interventions with adult ATS users (aged 18 years or older) diagnosed by any explicit diagnostic system. Primary outcomes included abstinence rate and other indicators of drug-using behaviours. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Only two studies met the eligibility criteria. Both studies were at low risk of selection bias and reporting bias. In one study, almost half of participants in the intervention group dropped out and this study was at high risk of attrition bias. The studies compared a single session of brief CBT or a web-based CBT to a waiting-list control (total sample size across studies of 129). Results were mixed across the studies. For the single-session brief CBT study, two out of five measures of drug use produced significant results, percentage of abstinent days in 90 days (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.11) and dependence symptoms (standardised mean difference (SMD) -0.59, 95% CI -1.16 to -0.02). Little confidence could be placed in the results from this study give the small sample size (25 participants per group) and corresponding large CIs around the observed effects. For the web-based CBT, there was no significant difference across different outcomes. Neither study reported adverse effects. The meta-analytic mean across these two trials for drug use was not significant (SMD -0.28, 95% CI -0.69 to 0.14). In summary, overall quality of evidence was low and there was insufficient evidence to conclude that CBT is effective, or ineffective, at treating ATS use. AUTHORS' CONCLUSIONS: Currently, there is not enough evidence to establish the efficacy of CBT for ATS-use disorders because of a paucity of high-quality research in this area.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/terapia , Anfetaminas , Terapia Cognitivo-Comportamental/métodos , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Anfetaminas/efeitos adversos , Feminino , Humanos , Masculino , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Listas de Espera
19.
Vet Clin North Am Small Anim Pract ; 48(6): 959-968, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30172446

RESUMO

Amphetamines and the nonamphetamine atomoxetine are commonly used in the treatment of attention-deficit disorder/attention-deficit/hyperactivity disorder in humans. Because these medications are often found in homes, dog and cat exposure to these medications is a common intoxication. Amphetamine intoxication can cause life-threatening central nervous system and cardiovascular stimulation, even when small amounts are ingested.


Assuntos
Inibidores da Captação Adrenérgica/efeitos adversos , Anfetaminas/efeitos adversos , Cloridrato de Atomoxetina/efeitos adversos , Doenças do Gato/induzido quimicamente , Doenças do Cão/induzido quimicamente , Inibidores da Captação Adrenérgica/farmacocinética , Anfetaminas/farmacocinética , Animais , Cloridrato de Atomoxetina/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Doenças do Gato/diagnóstico , Doenças do Gato/terapia , Gatos , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Cães , Humanos , Prognóstico
20.
J Addict Med ; 12(6): 474-480, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30095567

RESUMO

BACKGROUND: This study sought to examine the occurrence of the nonmedical use of prescription stimulants (amphetamines and methylphenidate) in a university sample and their associated physical and mental health correlates, including potential relationships with risky sexual practices. METHODS: A 156-item anonymous online survey was distributed via e-mail to a sample of 9449 university students. Current use of alcohol and drugs, psychological and physical status, and academic performance were assessed, along with questionnaire-based measures of impulsivity and compulsivity. RESULTS: A total of 3421 participants (59.7% female) were included in the analysis. 6.7% of the sample reported current/recent nonmedical use of prescription stimulants, while an additional 5.8% reported misuse in the past. Nonmedical use of prescription stimulants was associated with lower grade point averages, and with taking a broad range of other drugs (including alcohol, nicotine, illicit substances, and consumption of caffeinated soft drinks). Nonmedical use of stimulants was also significantly associated with impulsivity (Barratt scale), prior treatment for substance use problems, and elevated occurrence of disordered gambling, post-traumatic stress disorder, and anxiety; but not depression symptoms or binge-eating disorder (though it was associated with using drugs to lose weight). The relationship with probable attention-deficit/hyperactivity disorder (ADHD) on screening was not significant but was numerically elevated. Finally, those using nonmedical prescribed stimulants were significantly more sexually active (including at a younger age), and were less likely to use barrier contraception. CONCLUSIONS: Nonmedical use of prescription stimulants is common in young adults and has profound public health associations including with a profundity of other drug use (licit and illicit), certain mental health diagnoses (especially gambling, anxiety, and post-traumatic stress disorder ), worse scholastic performance, and riskier sexual practices. The majority of people with nonmedical use of prescription stimulants do not have ADHD, and its link with current ADHD symptoms was less marked than for certain other disorders. Clinicians should screen for the misuse of prescription stimulants as they may be associated with a range of problematic behaviors. Risk of diversion (which may be higher for those living in shared accommodation and those with substance use disorder history) merits careful assessment before prescribing stimulant medication.


Assuntos
Anfetaminas/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Comportamento Impulsivo/efeitos dos fármacos , Metilfenidato/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição/efeitos adversos , Assunção de Riscos , Comportamento Sexual/efeitos dos fármacos , Estudantes , Adolescente , Adulto , Feminino , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Desvio de Medicamentos sob Prescrição/estatística & dados numéricos , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Adulto Jovem
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