Development of a Brazilian anticholinergic activity drug scale / Desenvolvimento de uma escala brasileira de medicamentos com atividade anticolinérgica

ABSTRACT Objective To develop a scale of anticholinergic activity drugs used in Brazil, to be applied in health care and pharmacoepidemiology research. Methods We performed a literature review on PubMed/MEDLINE® to identify previously published scales of anticholinergic drugs. This scale started with anticholinergic drugs, and those with known anticholinergic activity as per the 4th level, chemical-therapeutic subgroup, of the Anatomical Therapeutic Chemical classification. We also included drugs with high anticholinergic activity, as described in a list of potentially inappropriate medications for use in older adults, according to the 2015 American Geriatrics Society Beers Criteria. Drugs listed in at least two anticholinergic scales were added. Then we verified which drugs in the previous steps were marketed in Brazil. We assigned a score of 1, 2 and 3, based on their anticholinergic action. Results A total of 273 anticholinergic drugs were identified, of which 125 were included in the scale. We identified 45 (36.0%) drugs with a score of 3, 13 (10.4%) with a score of 2, and 67 (53.6%) with a score of 1. Drugs for the nervous and respiratory systems were the most frequent in the scale. Eight drugs were not present in previous scales. Conclusion The methodology used for development of the Brazilian anticholinergic activity scale is simple, systematized, reproducible and easy to update. The scale allows evaluating the impact of anticholinergic burden on health outcomes, and can potentially contribute to pharmacoepidemiology research, leading to more accurate measurements of anticholinergic activity.

RESUMO Objetivo Desenvolver uma escala de atividade anticolinérgica abrangendo os medicamentos utilizados no Brasil, para aplicação no cuidado em saúde e em pesquisas farmacoepidemiológicas. Métodos Realizou-se revisão da literatura no PubMed/MEDLINE®para identificação das escalas de mensuração da atividade anticolinérgica. Iniciou-se a escala com os fármacos anticolinérgicos e aqueles com atividade anticolinérgica conhecida, relacionados segundo o nível 4, subgrupo químico, na classificação da Anatomical Therapeutic Chemical . Incluíram-se os fármacos com atividade anticolinérgica alta, descritos na lista de medicamentos potencialmente inapropriados para idosos, segundo o 2015 American Geriatrics Society Beers Criteria . Adicionaram-se os medicamentos que constavam em, no mínimo, duas escalas anticolinérgicas. Em seguida, verificaram-se os medicamentos constantes nas etapas anteriores comercializados no Brasil. A magnitude da atividade anticolinérgica foi estabelecida em escores com os valores de 1, 2 e 3. Resultados Foram identificados 273 medicamentos com atividade anticolinérgica, sendo 125 incluídos na escala. Destes, 45 (36,0%) receberam pontuação 3, 13 (10,4%) tiveram pontuação 2, e 67 (53,6%) pontuação 1. A maioria dos medicamentos da escala atuava nos sistemas nervoso e respiratório. Oito fármacos não constavam em escalas prévias. Conclusão A metodologia de desenvolvimento da escala brasileira de atividade anticolinérgica é simples, sistematizada, reprodutível e de fácil atualização. A escala permite avaliar o impacto da carga anticolinérgica nos resultados em saúde e pode contribuir com as pesquisas farmacoepidemiológicas, propiciando mensurações mais exatas da atividade anticolinérgica.

Anti-cholinergic alkaloids as potential therapeutic agents for Alzheimer’s disease: An in silico approach.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pleiocarpine showed promising anti-cholinergic potential, while its amino derivative showed about six-fold higher anti-cholinergic potential than pleiocarpine. Pleiocarpine and its amino derivative were found to be better inhibitors of AChE, as compared to commonly used drugs tacrine (brand name: Cognex) and rivastigmine (brand name: Exelon), suggesting development of these molecules as potential therapeutics in future.

Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats / Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico no tecido hipocampal de ratas ooforectomizadas e controles operadas sem ooforectomia

Different effects of scopolamine on learning, memory, and nitric oxide (NO) metabolites in hippocampal tissues of ovariectomized (OVX) and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco) and OVX-Scopolamine (OVX-Sco) Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001). Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001), while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.

Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico (ON) no tecido hipocampal de ratas ovariectomizadas (OVX) e controles com cirurgia sem ooforectomia (Grupo Sham) foram investigados. Os animais dos grupos Sham-Escopolamina (Sham-Sco) e OVX-Escopolamina (OVX-Sco) foram tratados com escopolamina 2 mg/kg antes de entrar no labirinto aquático de Morris, enquanto aqueles dos grupos Sham e OVX receberam solução salina. A latência de tempo e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Sco e OVX-Sco em comparação com os grupos Sham e OVX, respectivamente (p<0,001). Foram observados níveis significativamente mais baixos de metabólitos do ON nos hipocampos do Grupo Sham-Sco em comparação aos níveis do Sham (p<0,001), enquanto não foi observada diferença significativa entre os Grupos OVX-Sco e OVX. A diminuição do nível de ON no hipocampo pode ter um papel no aprendizado e nos déficits de memória induzidos pela escopolamina. No entanto, parece que este efeito da escopolamina no ON hipocampal é diferente em situações de presença ou ausência de hormônios ovarianos.

Resiniferatoxin for detrusor instability refractory to anticholinergics

PURPOSE: We have evaluated the clinical and urodynamic effects of intravesical instillation of resiniferatoxin in patients with idiopathic detrusor instability refractory to anticholinergics. MATERIALS AND METHODS: There were 30 women, median age 56 years old with detrusor instability for over 6 months and a history of anticholinergic use with no response or intolerable collateral effects. A 50 nM solution of resiniferatoxin was prepared for intravesical instillation. All patients were evaluated for urinary symptoms, as well as for urodynamic assessments before and 30 days after instillation. Tolerability was analyzed during the instillation. RESULTS: A clinical improvement was observed in 30 percent of the patients with urinary urgency and in 33 percent of the patients with urge-incontinence. The mean maximum cystometric capacity before application was 303.9 ± 78.9 and after application 341 ± 84.6. No significant difference was observed (p = 0.585). The mean maximum amplitude of the contractions diminished from 47.86 ± 29.64 to 38.72 ± 30.77 (p = 0.002). CONCLUSIONS: Resiniferatoxin, in this concentration, proved to be useful in a small percentage of patients regarding clinical detrusor instability. Maximum amplitude of the involuntary contractions was significantly reduced and in 33 percent patients the involuntary contractions disappeared. Further studies with different concentrations are recommended.

Síndrome anticolinérgico central por dosis terapéuticas de ciproheptadina: a propósito de un caso / Central anticholinergic syndrome secondary to therapeutic dosage of ciproheptadine. a case reports

Se presenta el caso de un niño de 10 años de edad, que sufrió el síndrome anticolinérgico central por la ingestión de dosis terapéuticas de ciproheptadina. Se aprovecha el tema para realizar una actualización de este síndrome.

Drug therapy of childhood asthma.

Drug therapy is used to prevent and control asthma, and also to reduce the frequency and severity of its exacerbations, and reverse airflow obstruction. Asthma medications are thus categorized into two general classes--bronchodilators (relievers) and anti-inflammatory drugs (preventers). Short acting beta2-agonists is the therapy of choice for relief of acute symptoms and prevention of exercise induced bronchospasm (EIB). Corticosteroids are the most potent and effective anti-inflammatory medication currently available. Inhaled form is used in the long-term control of asthma. Systemic corticosteroids are used to gain prompt control of the disease when initiating long-term therapy. Long acting bronchodilator used concomitantly with anti-inflammatory medications for long-term control of symptoms, especially nocturnal symptoms. Ipratropium bromide may provide some additive benefit to inhaled beta2-agonists in severe exacerbations. Sustained release theophylline is a mild to moderate bronchodilator used principally as adjuvant to inhaled corticosteroids for prevention of nocturnal asthma. Leukotriene modifiers may be considered as an alternative therapy to inhaled corticosteroids or cromolyn or nedocromil.

Intervención colinérgica en la enfermedad de Alzheimer y otras manifestaciones neuropsiquiátricas / Cholinergic intervention in Alzheimerïs disease and other neuropsychiatric manifestations

Las neuronas colinérgicas del telencéfalo basal suministran una profusa inervación a toda la corteza cerebral, constituyendose en el principal sistema modulador de la actividad cortical, participando en la regulación del estado de alerta y la atención. La denervación colinérgica, secundaria a la degeneración de estas neuronas en la enfermedad de Alzheimer, se relaciona directamente con el desarrollo de los síntomas de enfermedad, lo que ha impulsado la búsqueda de diversas formas de suplir la deficiencia de acetilcolina en la corteza. Hasta ahora los inhibidores de la acetilcolinesterasa han entregado los mejores resultados, pero estos no han sido más que modestos. En la presente revisión se examinan las bases fisiológicas y fisiopatológicas que avalan la intervención sobre el sistema colinérgico central y se examinan los resultados registrados en la enfermedad de Alzheimer y su extensión hacia otras manifestaciones neurosiquiátricas. Finalmente, se hace enfásis en que tratandose de una enfermedad degenerativa, lo más trascendente no es la disminución de un neurotransmisor, sino la perdida de las neuronas que los secretan y la interrupción de los circuitos en que estas neuronas participan

Revisión de los medicamentos antivertiginosos / a review of antivertigo medication

Objetivo. Valorar la información existente sobre los efectos de las sustancias antivertiginosas, basados en la bibliografía asequible. Información. Se localizaron artículos pertinentes en Medline y en revistas obtenidas en la ciudad de México. Selección del material. Los artículos se seleccionaron en base a su aparente consistencia interna y su relación con el propósito de la revisión. Conclusión. Se evaluaron 22 substancias pertenecientes a 8 grupos farmacológicos (colinérgicos, antihistamínicos, GABAérgicos, bloqueadores de canales de calcio, serotoninérgicos, hemorreológicos, antiagregantes plaquetarios y diuréticos) útiles en diversos padecimientos vertiginosos. Se advirtió la necesidad de un método objetivo y cuantitativo para valorar resultados de ensayos clínicos en humanos. Mientra esto no ocurra, tendremos que usar los medicamentos en base de una información veraz, confiable y basada sólidamente en la farmacología estudiada en experimentos con animales y en la valoración cuidadosa de los efectos -buenos y malos- observados en nuestros pacientes.

Bronchodilatory and anti-allergic effect of PulmoFlex--a proprietary herbal formulation.

PulmoFlex, a poly-herbal anti-asthmatic formulation has been reported to possess antihistaminic, mast cell stabilizing, anti-anaphylactic and antiallergic properties in experimental animals and clinical trials. The present study was undertaken to determine the effect of PulmoFlex on isolated perfused rat lung. The lung tissues were perfused at a pressure of 50 mmHg using oxygenated Krebs solution at 37 degrees C. PulmoFlex (1 & 2 mg/ml) increased the pulmonary perfusion flow indicating its bronchodilatory action. PulmoFlex (500 mcg) significantly prevented histamine (50 mcg), acetylcholine (50 mcg) and C-48/80 (10 mcg), induced bronchoconstriction indicating its antihistaminic, anticholinergic and mast cell stabilizing actions on pulmonary vascular beds and bronchioles, respectively. Lung tissue of sensitized (BSA) rats treated with PulmoFlex (20 mg/kg x 10 days) showed better perfusion following Ex vivo antigenic challenge as compared to untreated rats. This indicates the possibility of suppression of IgE mediated immune reaction by PulmoFlex. Thus, the present findings, suggest that PulmoFlex acts as an antiasthmatic by its bronchodilatory, membrane stabilizing, antihistaminic, anticholinergic and immunomodulatory (reaginic antibody mediated) effects.

Incontinência urinária na mulher. Enfase ao tratamento farmacológico / Female urinary incontinence: pharmacological treatment approach

A incontinência urinária feminina é uma entidade muito freqüente na prática urológica e ginecológica, tendendo a se acentuar no periódo pós-menopausa. Muitas pacientes apresentam graus leve e moderado de perda urinária involuntária e näo procuram cuidados médicos. Este trabalho tem a finalidade de chamar a atençäo do clínico para esta patologia, bem como de fazer uma revisäo atual e objetiva sobre as principais alternativas medicamentosas para o tratamento clínico (näo invasivo) da incontinência urinária na mulher.

Some pharmacological properties of Synclisia scabrida II.

The effect of the aqueous extract of S. scabrida on behaviour, and as an analgesic and antiulcer agent were studied. The extracts did not produce significant central nervous system action, or analgesia but had significant antiulcer activity against aspirin induced ulcer. The extract showed anticholinergic and antihistaminergic properties.

Drogas parassimpaticolíticas na terapêutica ocular / Parasympatholytics drugs in ocular therapeutic

Os autores fazem uma revisao dos aspectos farmacológicos de drogas anticolinérgicas na terapia ocular. É demonstrado o fármaco de escolha para algumas situaçoes práticas dentro da clínica oftalmológica e também se procede a um estudo comparativo entre essas mesmas drogas. Com isso, procura-se trazer ao clínico uma visao prática do uso desses fármacos, o que, certamente, contribuirá para esclarecer alguma situaçoes do dia-a-dia da práxis médica.

Noncompetitive inhibitors of the acetylcholine receptor help paint a picture of its ion channel

This review describes and analyzes the evidence from studies using noncompetitive inhibitors of the nicotinic acetylcholine receptor that the receptor's ion channel is formed by the second transmembrane segment of all five receptor subunits. Inconsistencies in this generally accepted model are also presented and discussed