RESUMO
ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.
RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.
Assuntos
Vitamina E/análise , Nicotina/farmacocinética , Pele/lesões , Adesivo TransdérmicoRESUMO
INTRODUCTION: Nicotine interacts with nicotinic acetylcholine receptors (nAChRs) and modifies neuronal functions. The net result of nicotine exposure is difficult to assess because multiple nAChR subtypes exist and are expressed on multiple classes of neurons. Nicotine, unlike the natural agonist acetylcholine, remains in tissues for hours, and during this extended exposure nAChRs desensitize. Therefore, agonists can block the natural functions of nAChRs. Higher nicotine concentrations are required to desensitize α4ß2-nAChRs containing the α5 subunit. The aim of these experiments was to determine if this property holds true for compounds other than nicotine. METHODS: [(3)H]-dopamine release from crude mouse striatal synaptosomal preparations was used to measure activation and desensitization of the [(α4ß2)2ß2] and [(α4ß2)2α5] nAChR subtypes. Affinity was measured by competition with [(125)I]-epibatidine. RESULTS: Nine compounds of varying affinity and efficacy were tested. All compounds partially desensitized both subtypes; concentration necessary for desensitization correlated with binding site affinity but not efficacy. All compounds showed a similar, significant shift in concentration necessary for a 50% effect when the α5 subunit was included (averaging 8-fold higher). The extent of desensitization produced by a 10-min exposure did not correlate with affinity or efficacy of compound. CONCLUSION: Full or partial nicotinic agonists used as medications may effectively desensitize α4ß2-nAChRs. However, significantly higher concentrations of all compounds tested were required to elicit desensitization of α4α5ß2-nAChRs than α4ß2-nAChRs. If desensitization is the important property for a smoking cessation drug, basic screening at both subtypes may provide a mechanistic foundation for effectiveness.
Assuntos
Dopamina/metabolismo , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Relação Dose-Resposta a Droga , Camundongos , Camundongos Mutantes , Nicotina/farmacocinética , Piridinas/metabolismo , Piridinas/farmacologia , Receptores Nicotínicos/genética , Abandono do Hábito de Fumar/métodosAssuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Tontura/induzido quimicamente , Debilidade Muscular/induzido quimicamente , Náusea/induzido quimicamente , Nicotiana/efeitos adversos , Nicotina/efeitos adversos , Vômito/induzido quimicamente , Pesquisa Biomédica , Saúde Global , Humanos , Nicotina/farmacocinética , Pele/metabolismoAssuntos
Humanos , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Tontura/induzido quimicamente , Debilidade Muscular/induzido quimicamente , Náusea/induzido quimicamente , Nicotina/efeitos adversos , Nicotiana/efeitos adversos , Vômito/induzido quimicamente , Pesquisa Biomédica , Nicotina/farmacocinética , Pele/metabolismo , Saúde GlobalRESUMO
Tobacco consumption is the main identifiable risk to cancer, contributing to the majority of tumors in upper aerodigestive tissues. The psychoactive compound responsible for tobacco addiction, nicotine and the potent carcinogens present at high concentrations either in cigarette mainstream smoke or in smokeless tobacco products, 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK) and N-nitrosonornicotine (NNN) can be metabolized by CYP2A6. CYP2A6 is expressed in many aerodigestive tissues with high interindividual variability. The CYP2A6 gene is highly polymorphic and CYP2A6 alleles coding for enzymes with altered expression or metabolic capacity produce alterations in nicotine metabolism in vivo and seem to influence smoking behavior. These polymorphisms may change the rate of NNK and NNN activation and, therefore, may influence cancer risk associated with tobacco consumption. However, to date only a few and inconclusive studies have addressed the risk that a given CYP2A6 polymorphism presents for the development of tobacco-related tumors. Most, but not all, show a reduced risk associated with alleles that result in decreased enzyme activity. The overlapping substrate specificity and tissue expression between CYP2A6 and the highly similar CYP2A13 may add to the conflicting results observed. The intricate regulation of CYP2A6 and the variation of structurally different chemical compounds capable of inhibiting CYP2A enzymes also add to the complexity. Finally, the interaction between polymorphisms of genes that code for CYP2A6, CYP2A13 and other potent carcinogen-metabolizing CYP enzymes may help to determine individuals that are at higher risk of developing tumors associated with tobacco consumption.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Carcinógenos/toxicidade , Neoplasias/genética , Nicotiana/toxicidade , Polimorfismo Genético , Carcinógenos/farmacocinética , Citocromo P-450 CYP2A6 , Humanos , Neoplasias/induzido quimicamente , Neoplasias/enzimologia , Nicotina/farmacocinética , Nicotina/toxicidade , Risco , Especificidade por Substrato , Nicotiana/químicaRESUMO
Smoking has a history almost as old as the own leaf of the tobacco, although in fact the act to smoke was restored in the general society after the discovery of America, considering itself even beneficial for the health, but fundamentally like a social and conventional conduct of the high nobility. In XVI century the first detractors began to appear but it was necessary many years to arrive the XX century when it was begun to relate the habit to tobacco and cancer, some years after the commercialization at industrial level of this habit. At the present the social awareness is tried towards the sanitary prevention. The declaration of Warsaw, the Marco Agreement and other sanitary measures forehead the habit to tobacco, are clear examples of this medical-social restlessness that tries to exile the smoking as a social, conventional and good seen conduct to try a prevention and a greater quality of life of the individuals.
Assuntos
Fumar/fisiopatologia , Tabagismo/fisiopatologia , Adulto , Animais , Doenças Cardiovasculares/etiologia , Predisposição Genética para Doença , Saúde Global , Medicina Herbária , Humanos , Neoplasias/etiologia , Nicotina/efeitos adversos , Nicotina/farmacocinética , Fatores de Risco , Fumar/efeitos adversos , Fumar/legislação & jurisprudência , Fumar/tendências , Prevenção do Hábito de Fumar , Nicotiana/efeitos adversos , Nicotiana/química , Poluição por Fumaça de Tabaco/efeitos adversos , Tabagismo/genética , Tabagismo/prevenção & controle , Tabagismo/psicologia , Organização Mundial da SaúdeRESUMO
Se realizó una intoxicación experimental en 70 personas jóvenes normales que produjo vértigo o desequilibrio. Se estudiaron dos parámetros: el nistagmo espontáneo y el posicional. Las drogas que se experimentaron fueron de uso común mientras que otras se usan por prescripción terapéutica. Estas drogas actúan sobre la homeostasis del sentido del equilibrio sea por efecto inhibitorio o exitatorio en diferentes niveles del sistema nervioso central. Las sustancias estudiadas fueron: alcohol, ketamina, pentobarbital, nicotina, xileno, etambutol, tricloroetileno, fentanil y droperidol. Todas las drogas, con excepción de la ketamina, produjeron nistagmo espontáneo y porsicional, en algunas personas contra la gravedad y en las otras a favor de ella. La información obtenida lo conduce a uno a predecir cuán mal se sentirá una persona después del uso de drogas como las fenotiazinas, dependiendo del nivel del sistema nervioso que es afectado o cuán bien se sentirá usando un agonista del GABA o un antagonista de acetilcolina, dependiendo del tipo del nistagmo espontáneo o posicional que afecte al paciente en el momento de usar alguna de estas drogas
Assuntos
Adulto , Vertigem/tratamento farmacológico , Nistagmo Patológico/induzido quimicamente , Equilíbrio Postural/efeitos dos fármacos , Tiopental/farmacocinética , Xilenos/farmacocinética , Fentanila/farmacocinética , Etanol/farmacocinética , Droperidol/farmacocinética , Etambutol/farmacocinética , Nicotina/farmacocinética , Ensaio Patogenético HomeopáticoRESUMO
Este artículo constituye una revisión del substrato neuroquímico de los efectos conductuales del etanol (ETOH), en especial sus propiedades gratificantes positivas y la tolerancia y dependencia física que su consumo produce, a partir de estudios en animales, haciendo referencia también a resultados obtenidos en humanos. La mayoría de los sistemas de neurotransmisión están involucrados en las acciones conductuales del ETOH, principalmente las monoaminas y los opioides. Sus efectos depresores a altas dosis, estimulantes a bajas dosis e hipotérmicos parecen tener bases distintas. Mientras que la activación catecolaminérgica está relacionada con los efectos estimulantes, los mecanismos gabérgicos están más involucrados con los depresores
Assuntos
Camundongos , Ratos , Animais , Humanos , Etanol/farmacologia , Acetilcolina/farmacocinética , Adenosina/farmacocinética , Benzodiazepinas/farmacocinética , Dopamina/farmacocinética , Ácido gama-Aminobutírico/farmacocinética , Glutamatos/farmacocinética , Morfina/farmacocinética , Nicotina/farmacocinética , Norepinefrina/farmacocinética , Serotonina/farmacocinéticaRESUMO
Most theories of dependence imply that repeated exposure to an addictive drug leads inexorably to dependence. We examined nicotine exposure in "tobacco chippers," who smoke regularly without developing dependence. Blood samples were obtained before and after 10 chippers (smoking up to 5 cigarettes per day) and 12 dependent smokers (20 to 40 cigarettes per day) smoked a cigarette. Chippers' blood nicotine levels increased significantly, in amounts equaling those of dependent smokers. Assays of cotinine (a long-lasting nicotine metabolite) also suggested that chippers' per-cigarette nicotine absorption equaled that of dependent smokers. Chippers' cotinine levels were also compared with those of heavy smokers (38 cigarettes per day) whose consumption was reduced to 5 cigarettes per day in a previously published study. The heavy smokers compensated by tripling their per-cigarette nicotine intake. Chippers did not seem to be compensating; their cotinine values equaled those expected when regular smokers were not compensating for reduced cigarette availability.