Consumption of drugs for Alzheimer's disease on the Brazilian private market / Consumo de medicamentos para doença de Alzheimer no mercado privado brasileiro

ABSTRACT OBJECTIVE To analyze the consumption of drugs for Alzheimer's disease on the Brazilian private market and its geographical distribution from 2014 to 2020. METHODS National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels. RESULTS Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020. CONCLUSION The consumption of medicines indicated to treat Alzheimer's disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.

RESUMO OBJETIVO Analisar o consumo de medicamentos para a doença de Alzheimer no mercado privado brasileiro e sua distribuição geográfica entre os anos de 2014 e 2020. MÉTODOS Foram utilizados dados do Sistema Nacional de Gerenciamento de Produtos Controlados relativos às vendas de donepezila, galantamina, rivastigmina e memantina, entre janeiro de 2014 a dezembro de 2020, em todo o território nacional. Os dados de venda foram utilizados como proxy para o consumo dos medicamentos, avaliado em dose diária definida (DDD)/1.000 habitantes/ano em nível nacional, regional, por unidade federativa e microrregião. RESULTADOS O consumo dos medicamentos passou de 5.000 DDD/1.000 habitantes em 2014 para mais de 16.000 DDD/1.000 habitantes em 2020, e todas as unidades de federação apresentaram variação positiva. A região Nordeste apresentou o maior consumo acumulado no período, porém exibiu disparidades microrregionais. A região Norte apresentou o menor consumo. Os medicamentos mais consumidos foram donepezila e memantina, os quais também apresentaram maior crescimento do consumo no intervalo de tempo entre os anos de 2014 e 2020. CONCLUSÃO O consumo de medicamentos para o tratamento da doença de Alzheimer triplicou no Brasil entre os anos de 2014 e 2020, o que pode estar relacionado ao aumento da prevalência da doença no país e/ou maior acesso a serviços de saúde, assim como estar ligado, também, à utilização inapropriada destes medicamentos. Este é um desafio para gestores e profissionais de saúde num cenário de envelhecimento populacional e aumento da prevalência de doenças crônico-degenerativas.

Influence of galantamine in the inflammatory process and tissular lesions caused by Trypanosoma cruzi QM2 strain

Abstract INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.

Efecto de Petiveria alliacea y drogas colinérgicas sobre la habituación / Effects of Petiveria alliacea and cholinergic drugs on the habituation cognitive behavior

Petiveria alliacea (PA) have anxiolytic, antidepressant and cognitive effects. In the present paper the effect of PA water infusion and cholinergic drugs on cognitive behavior were studied. For that, 40 male NMRI mice were divided in 4 groups: Control (n=10), Drug Control (n=10), PA (n=10) and PA plus Drug (n=10). PA 1% was administered orally (7.59±1.39 ml/day); while scopolamine (2 mg/Kg), galantamine (1 mg/Kg) and nicotine (0.1 mg/Kg) were administered intraperitoneally. Behavioral tests included: anxiety maze (AM), open field (OF) and marble burying (MB). Habituation cognitive behavior was evaluated in 4 sessions, one week each session. PA had anxiolytic and antidepressant effect effect in AM, combined with nicotine potentiated an anxiogenic effect in AM, galantamine favored habituation in OF. Scopolamine potentiated the habituation in LA and decreased the obsessive-compulsive behavior in OF. In conclusion; PA had an anxiolytic effect and favored deshabituation, combined with nicotine induced an anxiogenic effect, galantamine favored habituation and scopolamine decreased obsessive-compulsive behavior and favored motor habituation indicated a possible anxiolytic effect.

La Petiveria alliacea (PA) está relacionada con efectos ansiolíticos, antidepresivos y cognitivos. El presente trabajo estudió el efecto de la infusión de PA y drogas colinérgicas sobre la habituación. 40 ratones NMRI machos fueron divididos en 4 grupos: Control (n=10), Control Drogas (n=10), PA (n=10) y PA plus Drogas (n=10). La PA (1%) fue administrada vía oral (7.59±1.39 ml/día); escopolamina (2 mg/Kg), galantamina (1 mg/Kg) y nicotina (0.1 mg/Kg) fueron administrados vía intraperitoneal. Los ensayos conductuales incluyeron: laberinto de ansiedad (LA), campo abierto (CA) y enterramiento aversivo (EA). La habituación fue evaluada en 4 sesiones con duración de una semana cada una. PA mostró un efecto ansiolítico en el LA, combinada con nicotina potenció un efecto ansiogénico en el LA. Galantamina favoreció la habituación en CA, y escopolamina potenció el fenómeno de habituación en LA y disminuyó la conducta obsesivo-compulsiva en CA. En conclusión, la PA mostró un efecto ansiolítico y antidepresivo que potencia la deshabituación, combinada con nicotina indujo un efecto ansiogénico, galantamina favoreció la habituación y escopolamina disminuyó la conducta obsesivo­ compulsiva y favoreció la habituación motora indicando un posible efecto ansiolítico.

An Analysis on Prescribing Patterns of Alzheimer's Dementia Treatment and Choline Alfoscerate using HIRA Claims Data

BACKGROUND: Alzheimer's dementia is the most common dementia. However, recently, choline alfoscerate is prescribed for treating Alzheimer's dementia, although it is not a treatment for this disease. PURPOSE: To analyze the prescription patterns of choline alfoscerate as a dementia treatment for patients with Alzheimer's disease and to analyze, as well as the factors affecting choline alfoscerate prescription. METHOD: The 2016 HIRA-NPS data was used in this study. The code of Alzheimer's dementia is F00 in the ICD-10 disease classification code. We analyzed the demographic, clinical, and regional characteristics associated with donepezil, rivastigmine, galantamine, memantine, and choline alfoscerate prescriptions. All statistical and data analyse were conducted by SAS 9.4 and Excel. RESULTS: For patients with Alzheimer's disease, choline alfoscerate was the second most prescribed after donepezil. Analysis results showed that choline alfoscerate was more likely to be prescribed to men than to women, and more likely to be prescribed by local health centers than by medical institutions. Moreover, choline alfoscerate was highly likely to be prescribed at neurosurgical departments, among medical departments. CONCLUSION: This study confirmed that choline alfoscerate was prescribed considerably for patients with Alzheimer's dementia. Further studies valuating its clinical validity should be performed to clarify whether choline alfoscerate prescription is appropriate for treating Alzheimer's dementia.

Recent Advances in Diagnosis and Treatment of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder in which neuronal loss causes cognitive decline and other neuropsychiatric problems. It can be diagnosed based on history, examination, and appropriate objective assessments, using standard criteria such as the Diagnostic and Statistical Manual of Mental Disorders or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. The cholinesterase inhibitors, donepezil, rivastigmine and galantamine and N-methyl-D-aspartate receptors antagonist memantine are approved by the US Food and Drug Administration for AD. Recently some acetylcholinesterase inhibitors gained approval for the treatment of severe AD and became available in a higher dose formulation or a patch formulation. Optimal care in AD is multifactorial and it should include early diagnosis and multidisciplinary care with pharmacological and nonpharmacological interventions including exercise interventions, cognitive interventions and maintenance of social networks.

Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.

Efficacy of Galantamine on Cognition in Mild-to-Moderate Alzheimer's Dementia after Failure to Respond to Donepezil

OBJECTIVE: This study compares the efficacy of the cholinesterase inhibitor (ChEI) galantamine on cognition in patients with mild-to-moderate Alzheimer's dementia (AD) who were either naïve to ChEI drugs or who had failed a trial of the ChEI donepezil. METHODS: Outpatients with AD were sequentially referred for screening and enrollment. Current outpatients who had taken donepezil for at least 6 months without demonstrated efficacy on cognition were switched to galantamine (switched group). New outpatients with no ChEI prescription history were classified as the naïve group and were given galantamine. The primary outcome measures for the between-group comparison were response rate on cognition at 26 and 52 weeks (categorical) and change on the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (dimensional). Secondary cognitive outcomes were measured using the subset of frontal executive function and the Korean Mini-Mental State Examination. RESULTS: Seventy outpatients were enrolled and 66 were analyzed by Intent-to-treat (ITT). There were 42 cases in the naïve group and 24 in the switched group. Response rates did not differ at 26 weeks (71.4% naïve vs. 58.3% switched; p=0.277) or at 52 weeks (59.5% naïve vs. 41.6% switched; p=0.162). No significant differences were observed in the pattern of change over the 52 weeks on the primary and secondary cognitive scales. CONCLUSION: As the efficacy of galantamine on cognition was not inferior in the switched group compared to that in the naïve group, switching ChEI drugs is clinically feasible for non-responding patients with mild-to-moderate AD.

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

PURPOSE: To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35-treated mice. METHODS: PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method. RESULTS: Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function. CONCLUSION: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response in Alzheimer's disease in animals.

The Effects of Galantamine Treatment on Attention and Its Relationship with Cognition and Activities of Daily Living in Patients with Mild to Moderate Alzheimer's Disease

BACKGROUND AND PURPOSE: The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL. METHODS: In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL. RESULTS: After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216+/-3,650 sec; 12 weeks, 4,139+/-2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089+/-782 sec; 12 weeks, 908+/-606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial. CONCLUSIONS: This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.

Effects of galantamine and galantamine combined with nimodipine on cognitive speed and quality of life in mixed dementia: a 24-week, randomized, placebo-controlled exploratory trial (the REMIX study) / Efeitos da galantamina e da galantamina combinada à nimodipina sobre a velocidade de processamento cognitivo e qualidade de vida na demência mista: ensaio clínico exploratório, randomizado e controlado com placebo (estudo REMIX)

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate. Conclusion : GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658 .

Os efeitos da galantamina (GAL) sobre qualidade de vida (QdV) e velocidade de processamento cognitivo, bem como da combinação com nimodipina (NIM) no tratamento da doença de Alzheimer (DA) com doença cerebrovascular (demência mista) ainda não foram investigados. Método : Estudo multicêntrico brasileiro, duplo-cego, controlado com placebo, avaliando os efeitos de GAL/NIM x GAL/placebo (PLA) na demência mista leve a moderada. Pacientes receberam tratamento com GAL/NIM ou GAL/PLA por 24 semanas. Medidas de eficácia primária foram as variações no desempenho em bateria de testes neuropsicológicos computadorizados e na escala QdV-DA ao final do estudo. Resultados : Vinte um pacientes receberam pelo menos uma dose da droga (9 GAL/NIM e 12 GAL/PLA). Os grupos foram emparelhados por idade, sexo, escolaridade, escores cognitivos e de QdV na linha de base. Não foram observadas diferenças significativas entre os dois grupos nas medidas de eficácia primária e secundária. Na avaliação de todos os pacientes que receberam GAL, houve melhora significativa (p<0,05) em QdV-DA e desempenho cognitivo. Os eventos adversos foram predominantemente leves a moderados. Conclusão : O tratamento com GAL proporcionou melhora da QdV na demência mista, além dos benefícios cognitivos previamente conhecidos. A combinação GAL/NIM não foi vantajosa. O reduzido tamanho amostral impede conclusões definitivas. .

Effect of precursor on growth and accumulation of alkaloids of Lycoris radiata suspension cells / 生物工程学报

In order to investigate the effects of phenylalanine, tyrosine and tyramine on the growth of Lycoris radiata suspension cells and the accumulation of alkaloids, the growth quantity of the cells as well as the content of alkaloids in cells were determined, which were treated with above three kinds of precursors alone and phenylalanine combined with tyrosine respectively. The results indicate that the addition of phenylalanine alone and addition of phenylalanine on the basis of tyrosine at high concentration (200 micromol/L) had no significant effect on the growth of Lycoris radiata suspension cells and the content of alkaloids in cells; whereas tyrosine and tyramine promoted the growth of the cells and alkaloids accumulation. Treated with tyrosine at high concentration (200 micromol/L), the content of alkaloids of the cells was 2.56-fold higher than that of the control group, the amounts of lycoramine (3.77 mg/g) and galanthamine (4.46 mg/g) were 6.61-fold and 6.97-fold higher than that of the control group, respectively. When treated with tyramine (200 micromol/L), the amount of alkaloids in Lycoris radiata suspension cells was 2.63-fold higher than that of the control group, and the amounts of lycoramine (4.45 mg/g) and galanthamine (5.14 mg/g) were 9.08-fold and 9.18-fold higher than that of the control group, respectively. The above results demonstrate that adding tyrosine and tyramine in the media significantly promoted the growth of the Lycoris radiata suspension cells and alkaloids accumulation in the cells.

An LC-MS/MS method for the simultaneous determination of lycorine and galanthamine in rat plasma and its application to pharmacokinetic study of Lycoris radiata extract in rats / 华中科技大学学报（医学）（英德文版）

A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of lycorine and galanthamine, two major constituents in Lycoris radiata extract, in rat plasma. Liquid-liquid extraction with ethyl ether was carried out using diphenhydramine as the internal standard. The two bioactive alkaloids were separated on a Zorbax SB-C18 reserved-phase column (150 mm × 4.6 mm, i.d., 5 μm) by gradient elution using a mobile phase consisting of methanol with 0.1% formic acid (A) and water with 0.1% formic acid (B) at a flow rate of 0.6 mL/min. All analytes showed good linearity over a wide concentration range (r (2)>0.99) and the lower limit of quantification was 3.00 ng/mL for each analyte. The average extraction recovery of the analytes from rat plasma was more than 82.15%, and the intra-day and inter-day accuracy and precision of the assay were less than 12.6%. The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of two Amaryllidaceous alkaloids in rat plasma after an oral administration of Lycoris radiata extract.

Efectividad y seguridad de donepezilo, galantamina y memantina para el tratamiento de la Enfermedad de Alzheimer / Effectiveness and safety of donepezil, galantamine and memantine for the treatment of Alzheimer's disease

Antecedentes: Descripción de la condición de salud de interés: Las demencias son un grupo de trastornos del sistema nervioso central, caracterizados por alteración de la memoria, de las funciones ejecutivas, déficit cognitivo y cambios en la personalidad. La Enfermedad de Alzheimer es un tipo de demencia de inicio insidioso y progresión lenta, que compromete la memoria, el lenguaje, la personalidad y la función ejecutiva. Descripción de la tecnología: En general los medicamentos empleados en la enfermedad de Alzheimer ayudan a controlar los síntomas y manejar la agitación, la depresión o los síntomas psicóticos (alucinaciones o delirios) que pueden ocurrir cuando la enfermedad progresa. Evaluación de efectividad y seguridad: Pregunta de investigación: ¿Cuál es la efectividad y seguridad de donepezilo, memantina y galantamina comparado con rivastigmina para el tratamiento de la demencia por enfermedad de Alzheimer? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías, revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, entre otros), estudios de prevalencia/incidencia y carga de enfermedad y consulta con expertos temáticos (especialistas clínicos), sociedades científicas y otros actores clave. No se identificaron otros comparadores relevantes para la evaluación. Población: Hombres y mujeres adultos con enfermedad de Alzheimer. Conclusiones: La evidencia disponible sobre la eficacia de los inhibidores de acetilcolinesterasa (donepezilo, galantamina y rivastigmina) muestra un efecto sobre la cognición y la funcionalidad de los pacientes con enfermedad de Alzheimer moderada y severa. Las comparaciones directas disponibles y las comparaciones indirectas no permiten establecer la superioridad de alguno de los inhibidores de colinesterasa. La eficacia de la memantina para el manejo de la enfermedad de Alzheimer moderada en comparación con rivastigmina no ha sido evaluada en experimentos clínicos controlados. El perfil de seguridad de las intervenciones en estudio es similar al del comprador (rivastigmina).

Medicamentos utilizados para trastornos cognitivos: Análisis de un millón y medio de prescripciones en la Argentina / Drugs used for cognitive impairment: Analysis of 1.5 million prescriptions in Argentina

Los costos originados por trastornos cognitivos y demencias son significativos para los sistemas de salud. Según guías nacionales e internacionales, los fármacos recomendados para su tratamiento son inhibidores de colinesterasa (donepecilo, galantamina y rivastigmina) y memantina. En la Argentina también son utilizados otros nootrópicos, galantamina, rivastigmina, vasodilatadores, vitaminas y antioxidantes. El objetivo del presente estudio es describir y comparar el patrón de prescripción de drogas para el tratamiento de trastornos cognitivos y demencias en las distintas regiones del país. Se realizó un estudio observacional retrospectivo a partir de las prescripciones (1 814 108 envases) realizadas en la práctica clínica habitual durante el segundo semestre del 2008 y el primer y segundo semestre del 2009. El trabajo fue realizado sobre la población total del Instituto Nacional de Servicios Sociales para Jubilados y Pensionados. Se analizaron variables demográficas, cantidad y tasa de prescripciones, presentaciones y dosis utilizadas por regiones. Considerando todo el país, memantina fue la droga más prescripta en esos períodos, con un total de 570 893 envases. Memantina, donepecilo, rivastigmina e idebenona presentaron un incremento en las tasas de prescripción 2008-2009. Analizando los cambios regionales en tasas de prescripción, la memantina aumentó en el Noroeste y Noreste argentino, la idebenona en el Noroeste y la Patagonia y el donepecilo en el Noreste. Grupos de fármacos no recomendados fueron altamente prescriptos en todas las regiones del país. Algunos fueron indicados en adultos jóvenes o de mediana edad.

Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1 814 108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina´s regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570 893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.

Effects of Single Treatment of Anti-Dementia Drugs on Sleep-Wake Patterns in Rats

We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance.

Effects of Galantamine Treatment on Attention, Activities of Daily Living, and Neuropsychiatric Symptoms between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of galantamine treatment, especially attention ability between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 24-week trial. METHODS: A total of 40 patients were recruited for this 24-week study. The effect of galantamine on attention was measured using Seoul Computerized NeuroCognitive Function Test (SCNT) and frontal functions test of Seoul Neuropsychological Screening Battery (SNSB). Patients'activities of daily living using the Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL) ; behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline and 24-week. RESULTS: 17 pure AD patients and 23 MD patients were analyzed in this study. Attention as measured by SCNT was not significantly different from baseline after 24 weeks of treatment in both groups. There was no significant difference between two groups in mean change from baseline in the SCNT, S-ADL, S-IADL and K-NPI scores at 24-week. CONCLUSION: Galantamine showed a therapeutic effect on cognition, activities of daily living, neuropsychiatric symptoms in pure AD and MD. Furthermore, Galantamine may specifically help to maintain attention and it may have positive effects on other cognitive and functional abilities.

Reversible acetylcholinesterase inhibitory effect of Tabernaemontana divaricata extract on synaptic transmission in rat CA1 hippocampus.

Background & objectives: Acetylcholinesterase inhibitors (AChE-Is) are used for the treatment of Alzheimer’s disease (AD). These drugs including galanthamine have been shown to modulate synaptic activity in hippocampus and improve memory processes. Although Tabernaemontana divaricata extract (TDE) has been used as traditional medicine for various pharmacological effects, its effect in enhancing cholinergic activity provides additional benefit to its known effects. We investigated whether TDE can modulate the synaptic function in hippocampus and compared its effects to those of galanthamine. Methods: Hippocampal slices were prepared from male wWistar rats, functional effects of TDE were characterized by using pharmacological tools and extracellular recordings of field excitatory postsynaptic potentials (fEPSPs). Results: TDE significantly reduced fEPSPs. The fEPSPs reduction was prevented by atropine, but not pancuronium. These TDE effects were similar to those of galanthamine. Interpretation & conclusions: Our findings indicate that TDE can effectively modulate synaptic responses in the hippocampus similar to galanthamine, suggesting that this traditional medicine could be beneficial in ageing with ACh deprivation in the brain.