Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

Severe pertussis in childhood: update and controversy - systematic review / Coqueluche grave na infância: atualização e controvérsias - revisão sistemática

ABSTRACT Objective: Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic therapy and auxiliary therapeutic options for symptomatology and complications. Data sources: This review considered publications from the last 30years in the databases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane, Google Scholar, as well as protocols of the Ministry of Health and recommendations of the Centers for Disease Control and Prevention, related to childhood pertussis (whooping cough), with emphasis on its severe form. This research was based on keywords derived from the terms "pertussis", "azithromycin", "antitussives", "leukocyte reduction" in Portuguese and English. Duplicate studies and those with unavailable full-text were excluded. Data synthesis: Among 556 records found, 54 were selected for analysis. Pertussis, as a reemerging disease, has affected all age groups, evidencing the transient immunity conferred by infection and vaccination. Severe cases occur in neonates and infants, with secondary viral and bacterial complications and malignant pertussis, a longside hyperleukocytosis, respiratory failure and shock. Macrolides continue to be the chosen antibiotics, while antitussives for coughing remain without efficacy. The prompt treatment in Intensive Care Units improved the prognostic in severe cases, and transfusion was promising among procedures for leukoreduction. Conclusions: Approaching severe pertussis in childhood remains a challenge for diagnostic and therapy, as the available therapeutic options are still unsatisfactory. Strategies of prevention are expected to reduce the occurrence of severe cases, while new studies should confirm the role of auxiliary therapies.

RESUMO Objetivo: Rever os conceitos de coqueluche grave, atualizar epidemiologia, fisiopatologia e apresentação clínica, verificar as recomendações de antibioticoterapia e conhecer opções terapêuticas auxiliares na sintomatologia e complicações, por meio de revisão sistemática. Fontes de dados: Foram pesquisados trabalhos publicados nos últimos 30 anos nas bases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane e Google Scholar, bem como protocolos do Ministério da Saúde e recomendações do Centers for Disease Control and Prevention, relacionados à coqueluche na infância, com ênfase na forma grave. Apesquisa baseou-se em palavras-chave derivadas dos termos "coqueluche", "azitromicina", "antitussígenos" e "redução de leucócitos", nos idiomas português e inglês. Foramexcluídos estudos em duplicata ou texto integral indisponíveis. Síntese dos dados: Dos 556 registros encontrados, foram selecionados 54 para análise. A coqueluche, como doença reemergente, tem acometido todas as faixas etárias, evidenciando a imunidade transitória conferida pela infecção e pela vacinação. Quadros graves ocorrem em neonatos e lactentes, com complicações virais e bacterianas secundárias e pertussis maligna, com hiperleucocitose, insuficiência respiratória e choque refratário. Os macrolídeos continuam como antibióticos de escolha. Os sintomáticos da tosse não demonstraram eficácia. O suporte precoce em Unidade de Terapia Intensiva melhorou o prognóstico dos casos graves e a exsanguineotransfusão se mostrou a mais promissora entre os procedimentos para leucorredução. Conclusões: A abordagem da coqueluche grave na infância segue como desafio diagnóstico e terapêutico. As opções terapêuticas disponíveis ainda são insatisfatórias. Espera-se que as estratégias de prevenção reduzam a ocorrência de casos graves e que novos estudos confirmem o papel das terapias adjuvantes.

Antitussives, mucolytic agents and expectorants in clinical practice / 대한내과학회지

Cough is a protective reflex and also a common symptom of many respiratory diseases. The basic principle of management in chronic cough is treatment of its underlying cause. However, certain situations will necessitate cough suppressant therapy on a short-term basis for symptomatic relief of cough. Antitussives, expectorants and mucolytic agents are often used as the cough suppressant. Most of these drugs, however, are not consistently effective in reducing cough in adequately performed clinical trials. The aim of this brief review is to provide the list and some rationale for the currently available antitussive agents to practitioners.