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Br J Clin Pharmacol ; 83(4): 855-862, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27785820


AIMS: Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). METHODS: NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. RESULTS: Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. CONCLUSIONS: Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives.

Anti-Inflamatórios não Esteroides/envenenamento , Ácido Mefenâmico/envenenamento , Síndromes Neurotóxicas/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Criança , Pré-Escolar , Diclofenaco/administração & dosagem , Diclofenaco/envenenamento , Relação Dose-Resposta a Droga , Overdose de Drogas , Feminino , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/envenenamento , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Ácido Mefenâmico/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Naproxeno/administração & dosagem , Naproxeno/envenenamento , Síndromes Neurotóxicas/epidemiologia , Centros de Controle de Intoxicações , Fatores Sexuais , Reino Unido/epidemiologia , Adulto Jovem
Clin Toxicol (Phila) ; 54(8): 638-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27251903


CONTEXT: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects. OBJECTIVE: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA. MATERIALS AND METHODS: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE REPORTS: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine. CONCLUSIONS: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions.

Agonistas de Receptores de Canabinoides/toxicidade , Indóis/toxicidade , Psicotrópicos/toxicidade , Drogas Ilícitas/toxicidade , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Agonistas de Receptores de Canabinoides/sangue , Agonistas de Receptores de Canabinoides/urina , Cromatografia Líquida , Humanos , Indóis/sangue , Indóis/urina , Masculino , Pessoa de Meia-Idade , Psicotrópicos/sangue , Psicotrópicos/urina , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/urina , Espectrometria de Massas em Tandem , Reino Unido , Adulto Jovem
Emerg Med J ; 32(5): 383-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24957806


OBJECTIVE: 2,4-Dinitrophenol (DNP) increases energy consumption by uncoupling oxidative phosphorylation. Although not licensed as a medicine, it is sometimes used by 'body sculptors' and for weight loss as a 'fat burning' agent. This research was performed to characterise patterns of presentation, clinical features and outcomes of patients reported to the National Poisons Information Service (NPIS) in the UK after exposure to DNP. METHODS: NPIS telephone enquiry records and user sessions for TOXBASE, the NPIS online information database, related to DNP, were reviewed from 1 January 2007 to 31 December 2013. RESULTS: Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period (27 males, 3 females, with a median age of 23.5 years), there were 3 during 2007-2011 (inclusive), 5 during 2012 and 22 during 2013. TOXBASE user sessions also increased sharply from 6 in 2011 to 35 in 2012 and 331 in 2013. The modes of exposure reported in telephone enquiries were chronic (n=2), acute (n=12) and subacute (n=16). Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%), nausea or vomiting (27%), skin discolouration or rash (23%), breathing difficulties (23%), abdominal pain (23%), agitation (13%) and headache (13%). There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose. CONCLUSIONS: The study indicates a substantial recent increase in clinical presentations with toxicity caused by exposure to DNP in the UK with an associated high mortality. Further steps are needed to warn potential users of the severe and sometimes fatal toxicity that may occur after exposure to this compound.

2,4-Dinitrofenol/efeitos adversos , Suplementos Nutricionais/efeitos adversos , 2,4-Dinitrofenol/envenenamento , Dor Abdominal/induzido quimicamente , Adolescente , Adulto , Acatisia Induzida por Medicamentos , Criança , Suplementos Nutricionais/envenenamento , Dispneia/induzido quimicamente , Exantema/induzido quimicamente , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Masculino , Náusea/induzido quimicamente , Centros de Controle de Intoxicações , Sudorese/efeitos dos fármacos , Taquicardia/induzido quimicamente , Reino Unido , Vômito/induzido quimicamente , Adulto Jovem
Clin Toxicol (Phila) ; 52(10): 1025-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25345418


OBJECTIVE: To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use. METHODS: NPIS patient-specific telephone enquiries and user sessions for TOXBASE(®), the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period. RESULTS: There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE(®) user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE(®) sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27-7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29-4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%). CONCLUSIONS: Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently following reported ingestion of benzofuran compounds than after ingestion of mephedrone.

Benzofuranos/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Serviços de Informação sobre Medicamentos , Overdose de Drogas/epidemiologia , Centros de Controle de Intoxicações , Drogas Ilícitas/envenenamento , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Bases de Dados Factuais , Overdose de Drogas/diagnóstico , Feminino , Humanos , Internet , Masculino , Metanfetamina/análogos & derivados , Metanfetamina/envenenamento , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Telefone , Fatores de Tempo , Reino Unido/epidemiologia , Adulto Jovem
Libyan J Med ; 9(1): 24292, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28156274