Humanização dos serviços farmacêuticos

Vídeo das acadêmicas de Farmácia Bibiana Aldrigui e Thays Hennig Silva, elaborado para a disciplina de Seminário Integrador I. — em Unifra – Centro Universitário Franciscano, Santa Maria.

 

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Descoberto novo medicamento que reduz risco de AVC

Na semana em que AVC foi destaque dos noticiários devido ao caso do técnico Ricardo Gomes…

Um estudo encomendado pelos laboratórios americanos Bristol-Myers Squibb (BMS) e Pfizer revelou que uma nova molécula é eficiente na redução da frequência de acidentes vasculares cerebrais (AVC). A pesquisa foi feita com 18.201 pacientes e demonstrou a superioridade do novo medicamento sobre o tratamento de referência normalmente utilizado nos pacientes que sofrem de fibrilação arterial.

O estudo da fase III (a última antes da solicitação da comercialização do medicamento) revelou que para estes pacientes o apixaban seria o primeiro anticoagulante que reduz significativamente o risco de morte em função do problema, segundo o comunicado dos laboratórios.

Os pacientes que tomaram o novo remédio apresentaram uma probabilidade inferior a 21% de padecer de um AVC em relação aos pacientes tratados com warfarin. Além disso, tiveram 31% menos probabilidades de sofrer com uma hemorragia importante e risco 11% menor de morrer.

Os resultados foram apresentados ontem durante o Congresso da Sociedade Europeia de Cardiologia em Paris e publicados no jornal especializado New England Journal of Medicine.

O estudo, realizado em 1.034 hospitais de 39 países, foi coordenado pelo Duke Clinical Research Institute (Carolina do norte, sul dos Estados Unidos) e pelo Uppsala Clinical Research Institute (Suécia). Segundo os autores, 5 milhões de americanos e 6 milhões de habitantes da União Europeia sofrem de fibrilação arterial, a forma mais comum de perturbação do ritmo cardíaco, o que os coloca na categoria de risco de sofrer AVC.

FONTE: clicrbs

Caros leitores, não esqueçam do olhar crítico sobre pesquisas com CONFLITO DE INTERESSES!

 

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As palavras do cuidado….

Senhores aspirantes ou já farmacêuticos, revolucionários e motivados a buscar transgredir paradigmas seculares de apatia, prestem atenção:

 

“palavras não são más/ palavras não são quentes/ palavras são iguais/ sendo diferentes”.

Às vezes, a maneira como dizemos interfere muito mais no que dizemos. Dependendo da forma como dizemos “bom dia”, a pessoa pode pensar: “Já pensou quando não for um bom dia?”, ou ela pode, realmente, ter vontade de resgatar o seu dia.

 

“os números para os dias/ os nomes para as pessoas”.

Não existe processo de humanização hospitalar se não resgatarmos o nome das pessoas; entendamos que os números são para os dias e os nomes para as pessoas, todas elas.

 

“palavras eu preciso/ preciso com urgência/ palavras que se usem em casos de emergência”.

Por muito tempo, podemos pensar que as palavras que usamos em casos de emergência são: “parada cardiorrespiratória”, “fogo”, “socorro”, mas hoje, refletindo sobre a fala dos pacientes, podemos perceber que as palavras que podemos usar em casos de emergência são: “desculpe”, “sinto muito”, “estou fazendo tudo o que posso”, “estou com você”, “não tive a intenção”, enfim são as palavras que, com o tempo,  eles irão se lembrar, sabendo que fizemos o melhor em uma situação de emergência.

 

Sábias PALAVRAS de Maria Júlia Paes da Silva.

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Como abordar o paciente dependente de álcool?

 
A dependência de álcool é uma das doenças psiquiátricas de maior
prevalência. No Brasil, estima-se (não há estatísticas oficiais) que em
torno de 15% da população tenha problemas com o uso de álcool. Em
pesquisa nos Estados Unidos, encontrou-se uma prevalência do diagnóstico
de dependência de álcool durante a vida /(lifetime prevalence) /de 20,1 %.

Devido a sua alta prevalência e os efeitos devastadores sobre os vários
sistemas do organismo, o alcoolista está presente na clientela de
praticamente todas as especialidades médicas.

Na infecção pelo HIV, o alcoolismo é ainda mais freqüente. Os
homossexuais e usuários de drogas, parcela considerável dos pacientes
infectados, apresentam prevalência ainda maior de abuso e dependência de
álcool. Outro fato importante é que o uso de álcool é associado a sexo
de risco (sem preservativos) em populações de jovens heterossexuais.

O tratamento de pacientes com dependência de álcool é complexo e com
resultados ainda pouco animadores. O índice de abandono de tratamento e
recaídas são altos.

A abordagem do alcoolista infectado pelo HIV não é diferente do
não-infectado. Alguns aspectos básicos do tratamento são listados a seguir:

1. É importante estabelecer um bom vínculo com o paciente. Julgamentos
morais impedem o estabelecimento de uma boa relação médico-paciente,
essencial nestes casos.

2. O profissional deve encarar o alcoolismo como doença e não corno*
*"sem-vergonhice".

3. As diversas formas de tratamento não são excludentes e podem ser
empregadas concomitantemente (farmacologia, psicoterapia, abordagem
familiar, grupos de auto-ajuda - Alcoólatras Anônimos grupos religiosos,
entre outros).

4. As recaídas fazem parte da evolução e não devem ser vistas
necessariamente como falha terapêutica.

5. A parada da ingestão do álcool deve ser abrupta e almeja-se a
abstinência total na grande maioria dos casos.

6. Não se deve tolerar o uso da substância na institutição nem a vinda
do paciente intoxicado à consulta.

O tratamento apresenta duas etapas:

    - Desintoxicação e tratamento da abstinência. Uso de
    benzodiazepínicos, suplementação vítamínica e medidas de suporte.

    - Prevenção de recaídas. Psicoterapia e uso de fármacos em
    determinados casos. Para tratamento do alcoolismo pode-se utilizar
    medicação aversiva (antabuse) ou antagonista dos receptores opióides
    - naltrexone - que diminui o desejo de beber e a gravidade das recaídas.

 

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Tratamento farmacológico da fibromialgia

Purpose. Published evidence on the pathophysiology, diagnosis, and treatment of fibromyalgia is reviewed, with an emphasis on recent clinical trials of various pharmacologic agents.
Summary. Fibromyalgia affects an estimated 2% of the general U.S. population, and its incidence is sevenfold higher among women. The diagnostic characteristics of fibromyalgia are chronic widespread pain, thought to arise from abnormalities of ascending pain and descending inhibitory sensory pathways, and allodynia on palpation of specific tender points. Three medications available in the United States are labeled for treatment of fibromyalgia-related symptoms: the serotonin- and norepinephrine-reuptake inhibitors duloxetine and milnacipran and the α₂-δ ligand pregabalin. Evidence from clinical trials indicates that all three drugs can have a significant impact on fibromyalgia-related pain; duloxetine and pregabalin have been demonstrated to reduce sleep disturbances and improve quality of life (the former also has been shown to improve mood), while milnacipran can offer significant benefits in reducing fatigue. A growing body of evidence suggests that the best treatment approach may involve the use of one or more agents whose mechanisms of action are aligned with patient-specific clusters of symptoms. Several other agents have been used for fibromyalgia, with mixed results, including tricyclic antidepressants, selective serotonin-reuptake inhibitors, opioids, and gabapentin. Given the limitations of the evidence from clinical trials to date, controlled trials directly comparing different agents are needed to better delineate adverse-event risks, cost considerations, and optimal management approaches.
Conclusion. A broad range of drugs has been used to treat fibromyalgia. Symptoms, comorbidities, adverse effects, and patient preference are important considerations in drug selection.

Para ler o texto na íntegra, acesse Medscape Pharmacist 

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Uso de fitoterápicos, plantas medicinais e suplementos em bebês de até 1 ano de idade

Clinical Context

Dietary botanical supplements and herbal tea use are not regulated in the United States as pharmaceuticals are. In fact, some of these supplements may cause drug interactions or contain heavy metals, which, in infants, may have more adverse effects. Use of these dietary botanical supplements and teas among infants has not been well documented. This is an analysis of the cohort of mothers form the Infant Feeding Practices Study II to examine the prevalence of dietary botanical supplements and tea use in infants, reasons for use, and factors associated with use.

Study Highlights

•Included were 2653 healthy mothers with healthy term infants from the Infant Feeding Practices Study II. These mothers were surveyed longitudinally from pregnancy through the first year of their infants’ lives between 2005 and 2007.

•The cohort was drawn from a national consumer panel of mothers 18 years and older.

•Mothers were sent a questionnaire once during pregnancy and 10 times during the first year of their infants’ lives.

•94% of the postnatal sample returned at least 2 questionnaires.

•The sample overrepresented white, older, and better-educated mothers.

•The dependent variable was the number of times mothers answered “yes” to 10 postnatal survey questions asking about use of dietary botanical supplements or teas in their infants.

•Independent variables included age of the mothers, race/ethnicity, education, socioeconomics, breast-feeding practices, parity, and region.

•For each questionnaire, mothers were asked to list all dietary botanical supplements and teas their babies had been given in the past 2 weeks. •One third of mothers were 25 to 29 years old, 30% were 30 to 34 years old, and 72% were multiparous.

•Mean breast-feeding duration was 23.4 weeks; 85% of mothers were non-Hispanic white, and 6% were Hispanic.

•Overall, 9% of mothers in the sample reported giving dietary botanical supplements and teas to their infants on at least 1 questionnaire.

•4% of mothers reported giving dietary botanical supplements or teas to their infants on more than 1 questionnaire.

•Mothers were more likely to give their infants dietary botanical supplements or teas if they were users of dietary supplements themselves, were primiparous, older, had a higher education or income, and were married.

•Geographically, dietary botanical supplements and teas were more likely to be given in the West and least likely to be given in the Midwest.

•The odds ratio of giving infants dietary botanical supplements or teas was 3.69 among mothers who previously used such supplements themselves vs those who did not (P < .0001), and 1.85 among Hispanic mothers vs white mothers (P = .016). The odds were also increased among mothers with longer breast-feeding duration (P < .0001).

 •Parity, age, poverty, marital status, and region were no longer significant in the multivariate model.

•The percentage of infants given any dietary botanical supplements or teas ranged from 2.4% in month 1 to 4.4% in months 4 to 6.

•The most commonly used dietary botanical supplements and teas were gripe water, chamomile, teething tablets, and unspecified tea.

•The most common reasons given by mothers were to help with fussiness, digestion, colic, and relaxation in their infants.

•The most commonly reported sources of information regarding dietary botanical supplements and teas were friends and relatives (30%), healthcare providers (27%), and the media (27.6%).

•Mothers who received information from these sources were 3 to 5 times more likely to give their infants dietary botanical supplements and teas than mothers who did not.

•The authors concluded that use of dietary botanical supplements and teas occurred commonly among infants but that duration was short, and mothers who used these supplements themselves were more likely to give them to their infants. Clinical Implications

•An estimated 9% of mothers report use of dietary botanical supplements or teas for their infants in the first year of life. Maternal use, Hispanic race, and breast-feeding are associated with increased use of these supplements.

•Mothers who receive information about dietary botanical supplements and teas from friends or relatives, healthcare providers, or the media are more likely to give these supplements to their infants.

Fonte:  Laurie Barclay, MD
Medscape Pharmacist

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Exercícios de revisão

A lista de casos abaixo representa problemas relacionados a medicamentos. Classifique-os de acordo com o Consenso de Granada, de acordo com a Necessidade (1 ou 2), Eficácia (3 ou 4) e Segurança (5 ou 6), justificando a classificação.

1. José toma 80 mg de sinvastatina por dia para hiperlipiemia e seu colesterol permanece elevado. Uma contagem dos comprimidos sugere que ele toma o medicamento de acordo com a prescrição mas a sinvastatina é ineficaz.
2. Mariana (47 anos) começou a tomar zolpidem 5mg na hora de dormir conforme necessário. Ela acorda de manhã muito zonza para dirigir ao trabalho de forma segura.
3. Tadeu tem depressão muito profunda não diagnosticada. Ele teria as condições apropriadas para receber a terapia medicamentosa se fosse diagnosticado.
4. Luis não tem plano de saúde que cubra os gastos com seu levodopa/carbidopa e entacapone para doença de Parkinson, então, como não pode comprá-lo sempre, ele toma seus medicamentos esporadicamente para que durem mais tempo.
5. Ruth está grávida de 6 semanas e apresenta uma prescrição nova para atorvastatina 20mg diariamente, escrita pelo cardiologista que ela visitou pela primeira vez.
6. Rui foi hospitalizado com dano renal e hepático moderado e está para começar nutrição parenteral total (NPT). O farmacêutico calcula que a necessidade de proteína do paciente é de 60g por dia. A ordem da prescrição durante o dia 1 de NTP instrui o setor de terapia intravenosa da farmácia a preparar uma bolsa 24h com 60g de aminoácidos.
7. Antônio tem mal de Parkinson com tremores que tornam quase impossível aplicar colírios para o glaucoma.
8. Daniel tem 8 anos e tem asma crônica persistente, sendo tratado com nebulizador de albuterol uma vez ao dia.
9. Sílvio é obeso com pressão sanguínea controlada por felodipino e começou uma dieta com suco de grapefruit.
10. Maurício viaja para trabalhar e mantém sua insulina no porta-luvas do carro.
11. Tereza está com dores de cabeça de enxaqueca apresentando nova prescrição para zolmitriptan do médico de família e spray nasal de sumatriptano de seu neurologista
12. Márcia tem arritmia cardíaca estabilizada com amiodarona e apresenta uma nova prescrição de sulfato de quinidina.
13. Sebastião pede um novo inalador de albuterol a cada duas a três semanas. O farmacêutico determina que a técnica de inalação dele é adequada mas o paciente reclama de falta de ar.
14. Um farmacêutico oferece um programa de avaliação sobre osteoporose. Maria tem “t-score” de -2,9, sugerindo que ela possa ter osteoporose e possa requerer terapia medicamentosa adicional.
15. A farmacêutica Francisca recebe uma receita do Dr. Waltmann para rosuvastatina, a única estatina que ele prescreve. Ela sabe que não é a estatina mais segura e nem é esse o medicamento de escolha para a maioria dos pacientes.
16. A farmacêutica Letícia recebe uma nova prescrição do Dr. Garcia de cotrimoxazol para um paciente que toma fenitoína para epilepsia.
17. Um paciente com dores de cabeça de enxaqueca recebeu uma receita médica de acetaminofeno com codeína 30mg, mas ainda está com muita dor
18. Um paciente de 78 anos apresentou nova prescrição de digoxina 0,25mg via oral uma vez ao dia por 30 dias, e descansando, seu batimento cardíaco é de 66.
19. Um paciente não pode arcar com o custo de sua receita de infliximabe para doença de Crohn grave.
20. Um paciente com asma crônica persistente é tratada somente com inalador de albuterol, usada conforme a necessidade.

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Como dar más notícias ao seu paciente?

 

Roteiro básico

Veja uma série de recomendações, baseadas no chamado Protocolo Spikes (modelo construído por estudiosos americanos visando transmitir o diagnóstico aos pacientes de câncer):

Objetivos

:: Escutar o paciente com a finalidade de conhecer o seu grau de informação sobre a doença, suas expectativas e seu preparo para receber a má notícia.

:: Transmitir informação médica de maneira inteligível, de acordo com as possibilidades, as necessidades e os desejos do paciente.

:: Dar suporte ao paciente, utilizando habilidades profissionais para reduzir o impacto emocional e a sensação de isolamento experimentados por quem recebe a má notícia.

:: Desenvolver uma estratégia, sob a forma de um plano de tratamento, com a contribuição e a colaboração do paciente.

Etapas e recomendações

ETAPA 1 – Como planejar a entrevista

:: Rever os dados que fundamentam a má notícia: resultados de exames, tratamentos anteriores, literatura médica e informações gerais sobre o paciente.

:: Avaliar seus próprios sentimentos – positivos e negativos – sobre a transmissão da má notícia para esse paciente.

:: Buscar ambiente com privacidade; informar sobre restrições de tempo ou interrupções que possam ser inevitáveis; desligar o celular ou pedir a um colega para atender.

:: Envolver pessoas importantes, se esse for o desejo do paciente.

:: Sentar-se e colocar-se disponível para o paciente.

ETAPA 2 – Como avaliar a percepção do paciente: “Antes de contar, pergunte”

:: Procurar saber como o paciente percebe sua situação médica (o que tem, se é sério ou não), o que já lhe foi dito sobre o seu quadro clínico e o que procurou saber por fontes leigas ou profissionais, internet etc., qual é a sua compreensão sobre as razões pelas quais foram feitos os exames.

:: Perceber se o paciente está comprometido com alguma variante de negação da doença: pensamento mágico, omissão de detalhes médicos essenciais, mas desfavoráveis sobre a doença ou expectativas não realistas do tratamento.

:: Corrigir desinformações e moldar a má notícia para a compreensão e a capacidade de absorção do paciente.

ETAPA 3 – Como avaliar o desejo de saber do paciente e obter o seu pedido por informações

:: Procurar saber, desde o início do tratamento, se o paciente deseja informações detalhadas sobre o diagnóstico, o prognóstico e os pormenores dos tratamentos ou se quer ir pedindo informações gradativamente.

:: Oferecer-se para responder a qualquer pergunta ou para falar com familiares ou amigos.

:: Negociar a transmissão de informação no momento em que se pedem exames: se o paciente vai querer detalhes sobre os resultados ou apenas um esboço que possibilite a discussão do plano de tratamento.

ETAPA 4 – Como transmitir a notícia e as informações ao paciente

:: Anunciar com delicadeza que más notícias estão por vir, dar tempo ao paciente para se dispor a escutá-las.

:: Evitar termos técnicos, adaptando-se ao vocabulário e ao nível de compreensão do paciente.

:: Evitar a dureza excessiva, amenizando a transmissão de detalhes desnecessários.

:: Informar aos poucos, buscando conferir o progresso de sua compreensão.

:: Quando o prognóstico é ruim, evitar transmitir desesperança e desistência, valorizando, ao contrário, os cuidados paliativos, o alívio dos sintomas e o acompanhamento solidário.

ETAPA 5 – Como validar a expressão de sentimentos e oferecer respostas afetivas às emoções dos pacientes (e de familiares)

:: Favorecer a expressão de pacientes e familiares sobre o impacto da má notícia, dando voz a seus sentimentos e emoções para ajudá-los a superar estados de choque e evitar o descontrole.

:: Acolher a legítima expressão de sentimentos de ansiedade, raiva, tristeza ou inconformismo de pacientes e familiares, dando-lhes algum tempo para se acalmarem e abrindo-lhes as possibilidades de continuidade do acompanhamento.

:: Buscar respostas de reconhecimento e sintonia afetiva, ensaiar perguntas exploratórias que favoreçam a expressão dos sentimentos e das preocupações em jogo, assim como afirmativas reasseguradoras da legitimidade dessas expressões para reduzir os sentimentos de isolamento do paciente e de familiares, expressar solidariedade e validar seus sentimentos e pensamentos.

ETAPA 6 – Como resumir e traçar estratégias

:: Resumir as principais questões abordadas e traçar uma estratégia ou um plano de tratamento para ajudar os pacientes a sentirem-se menos ansiosos e inseguros.

:: Antes de discutir um plano de tratamento, perguntar aos pacientes se eles estão prontos para essa discussão e se aquele é o momento.

:: Compartilhar responsabilidades na tomada de decisão com o paciente (o que pode também reduzir qualquer sensação de fracasso da parte do médico quando o tratamento não é bem-sucedido).

:: Avaliar o não entendimento de pacientes sobre a discussão, prevenindo sua tendência a superestimarem a eficácia ou não compreenderem o propósito do tratamento.

:: Ser honesto sem destruir a esperança ou a vontade de viver dos pacientes.

Fonte: Clic RBS

 

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Fármacos para diabetes: Metformina

Metformin is one of the oldest oral treatments to reduce hyperglycaemia in people with diabetes. Gastrointestinal side effects are common, and metformin should be used with caution in patients with renal impairment because of the slight risk of lactic acidosis. In the United Kingdom Prospective Diabetes Study (UKPDS) patients treated with metformin had a significant reduction in myocardial infarction and mortality that was not demonstrated in patients treated with sulphonylureas or insulin. The fact that metformin significantly reduces cardiovascular events plus reduces weight has meant that metformin is the drug of first choice in guidelines for the treatment of type 2 diabetes. There are no longer concerns about using metformin in patients with chronic heart failure, other than in patients with associated renal failure, or during episodes of acute left ventricular failure when metformin should be temporarily stopped.

Introduction

The prevalence of type 2 diabetes mellitus (T2DM) is reaching epidemic proportions. Metformin therapy has been used in the treatment of T2DM for many years. Despite an increased armoury of agents for treating hyperglycaemia, only metformin has been shown to improve prognosis as a primary end point in a randomised-controlled trial.^[1] Clinical studies have shown that the effects of metformin go beyond improving glycosylated haemoglobin (HbA_1c) and include reductions in cardiovascular end points. Despite the evidence base for the benefits of metformin, concerns remain about its side effects, including the perceived risk of lactic acidosis, particularly in the presence of cardiac and renal failure. Evidence confirming its safety, even in the setting of cardiac and renal failure, has resulted in metformin being accepted globally as the first-line treatment for overweight patients (body mass index [BMI] >25 kg/m²) with T2DM.

The proposed mechanisms of action of metformin, which are not fully understood, are illustrated in figure 1. It can lower blood glucose in several ways. It acts by countering insulin resistance, particularly in liver and skeletal muscle. It suppresses hepatic gluconeogenesis, increases peripheral insulin sensitivity in insulin sensitive tissues such as muscle and adipose tissue, and enhances peripheral glucose utilisation. The protective effect on the cardiovascular system cannot be fully explained by its blood glucose-lowering properties. These effects may be partly mediated via beneficial effects on circulating markers of endothelial function (vascular cell adhesion molecule-1 [VCAM-1], E-selectin), fibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) and chronic inflammation (C-reactive protein [CRP]). There are several other potential mechanisms postulated to explain the cardiovascular benefits beyond blood glucose lowering, including disruption of respiratory chain oxidation in mitochondria and activation of the enzyme adenosine monophosphate (AMP)-activated protein kinase (AMPK).^[2,3] AMPK is a protein kinase ubiquitously expressed in mammalian tissues and involved in regulating energy balance. Activation of AMPK stimulates adenosine triphosphate (ATP)-producing catabolic pathways, while inhibiting ATP-consuming anabolic pathways, thereby, maintaining cellular energy stores. In skeletal muscle, activation of AMPK increases glucose uptake and lipid oxidation. In liver, activation of AMPK inhibits gluconeogenesis and lipid synthesis but increases lipid oxidation. Finally, in adipose tissue, activation of AMPK reduces both lipolysis and lipogenesis. Therefore, activation of AMPK in skeletal muscle, liver and adipose tissue results in decreased circulating glucose, lipids and ectopic fat accumulation, as well as enhanced insulin sensitivity.

Metformin has a short half-life of around six hours and undergoes renal excretion with 90% being eliminated within 24 hours. It can be prescribed as 500 mg or 850 mg tablets. It should be started at the 500 mg dose and increased in weekly increments until the maximum tolerated dose is achieved, normally 2 g/day. It should be taken with food to reduce the potential for gastrointestinal side effects. Occasionally higher doses are given depending on clinical response and tolerability. Hypoglycaemia is not usually a side effect of metformin therapy and it tends not to result in significant weight gain. The main side effect of concern is its association with lactic acidosis particularly in the setting of renal and cardiac failure.

Metformin is licensed to be given on its own in patients who have failed to improve with dietary modifications or it can be given in combination with sulphonylureas, thiazolidinediones, repaglinide/nateglinide, dipeptidyl peptidase-4 (DPP4) inhibitors (sitipliptin, vildagliptin, saxagliptin), glucagon-like peptide-1 (GLP-1) agonists (exenatide or liraglutide), acarbose or insulin. Indeed, given that the benefits of metformin are considered to go beyond glycaemic control, all overweight patients with T2DM should be on metformin, if tolerated. There is limited evidence to support the use of a slow-release preparation of metformin (Glucophage SR®) on the basis of fewer gastrointestinal side effects.

Evidence for Improved Glycaemic Control

The United Kingdom Prospective Diabetes Study (UKPDS) study, initiated in 1977 and reported in 1998, demonstrated that improved glycaemic control was associated with a reduced incidence of microvascular complications (such as nephropathy and retinopathy).^[1] While no significant effect of lowering blood glucose was observed on cardiovascular complications, epidemiological analysis of the UKPDS data has demonstrated a continuous association between the risk of cardiovascular complications and glycaemic control. Metformin has been shown to improve glycaemic control compared with placebo or diet. When compared with placebo, metformin shows improvement in HbA_1c and fasting plasma glucose, but there are no significant differences for BMI or weight, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, or blood pressure.^[4] When compared with diet, metformin shows improvement in HbA_1c and total cholesterol, but no difference for fasting plasma glucose, BMI or weight, HDL-cholesterol, LDL-cholesterol, triglycerides, or blood pressure. Metformin and sulphonylureas have similar effects on HbA_1c, and there is no significant difference in HbA_1c between those using metformin and those using insulin. UKPDS was the first randomised trial to demonstrate improved outcome with metformin treatment. The UKPDS trial allocated patients to either conventional (initial dietary modification with addition of a sulphonylurea for fasting plasma glucose >15 mmol/L) or a more intensive glycaemic control strategy (which could include metformin, sulphonylurea or insulin therapy).

Evidence for Cardiovascular Benefit

Within the UKPDS cohort there was a substudy looking at overweight patients (54% with obesity). Those allocated to metformin (n=342) had improved outcomes compared with those on conventional treatment (n=411). Randomisation to metformin was associated with dramatic relative risk reductions in diabetes-related death (–42%), myocardial infarction (–39%), stroke (–42%) any diabetes-related end point (–32%) and all-cause mortality (–36%) when compared with diet. This is in contrast to the relative risk reductions with sulphonylurea or insulin in diabetes-related death (–20%), myocardial infarction (–21%), stroke (‘14%) any diabetes-related end point (–7%) and all-cause mortality (–8%) when compared with diet. There were no significant differences between metformin and other comparison arms for other outcomes such as stroke, peripheral arterial disease and microvascular disease. Mean HbA_1c after follow-up in the diet group and metformin group were 8% and 7.4%, respectively, and there was no clear difference in the glucose-lowering effect between metformin, sulphonylurea and insulin.

Given that the glucose-lowering effects of metformin, sulphonylurea and insulin were similar, it has been proposed that metformin must confer additional vascular benefits beyond those of glycaemia alone. The UKPDS Post-Trial monitoring results suggest a legacy effect with continuing benefit of metformin therapy. There is maintenance of the relative risk reductions for any diabetes-related end point (–21%), myocardial infarction (–33%) and all-cause mortality (–27%), despite loss of within-trial blood glucose and therapy differences.^[5]

Discussion

Clinical studies in T2DM have shown that the effects of metformin go beyond improving HbA_1c and include reductions in cardiovascular end points. Metformin is considered to be the first drug of choice for the treatment of T2DM in overweight patients. There is increasing evidence to show that in the absence of tissue hypoxia and/or moderate-to-severe renal impairment, metformin will not result in lactic acidosis. Importantly, metformin should no longer be contraindicated in patients with chronic stable heart failure and may even have morbidity and mortality benefits. There is a clear need for prospective randomised-controlled studies of metformin therapy in patients with T2DM and the traditional contraindications of heart and renal failure. In the meantime, a pragmatic approach is recommended including temporarily stopping metformin during an acute illness where tissue hypoxia is suspected, which will include patients with an acute myocardial infarction, acute left ventricular failure or septicaemia, or when an individual is due to get radiological investigations using iodine-based contrast medium. Particular care should be taken in patients with chronic renal failure with a lower clinical threshold to temporarily discontinue in the aforementioned circumstances. However, chronic renal failure in itself is not an absolute contraindication to metformin use when the decision to prescribe or not is based on the potential prognostic benefits weighed against the likelihood of harm.

references

1. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854–65.
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Adverse Drug Events in Children: Recent Cases from the Medical Literature: Valproate-induced Metabolic Effects

New reports of ADEs appear in the medical literature each month. These publications can provide pediatric health care providers with valuable information to guide drug selection, dosing, and monitoring to avoid or reduce the potential for adverse events in their patients.

Adverse Events in Pediatric Intensive Care

A collaborative group of 15 PICUs published a retrospective evaluation of adverse events documented during the last four months of 2005. A total of 734 patient records were evaluated; 1,488 adverse events were identified, including 256 adverse drug events (ADEs). This resulted in a rate of 4.9 ADEs per 100 patient-days, or an adjusted cumulative risk for an ADE of 1.6% per PICU day. Surgical patients had a higher incidence of both adverse events and ADEs. There was also a relationship between the risk for ADEs and age, with a 4% increase in the adjusted ADE rate for every year increase in age. The authors suggest that these data may be useful in developing areas of focus for prevention strategies. Agarwal S, Classen D, Larsen G, et al. Prevalence of adverse events in pediatric ICUs in the United States. Pediatr Crit Care Med 2010; (epub ahead of print).

Analgesics and Anti-inflammatories in Sports

The June 2010 issue of Pediatric Clinics of North America includes an extensive review of the benefits and risks of analgesics and anti-inflammatory medications in young athletes. The authors describe the mechanism of action, pharmacokinetic and pharmacodynamic properties, and dosing recommendations for these drugs, as well as their adverse effect profiles. They include both oral agents and topical products. This article, with its extensive tables and bibliography, will be a useful reference for health care providers who provide care for adolescents with sports-related injuries. Feucht CL, Patel DR. Analgesics and anti-inflammatory medications in sports: use and abuse. Pediatr Clin N Am 2010;57:751–74.

Antiepileptic Safety Monitoring

Anderson and Choonara have studied the methods for ADE reporting during randomized controlled trials (RCTs) of antiepileptic drugs in children over the 10-year period from 1998 to 2007. Of the 29 RCTs identified, only three analyzed data from pediatric patients separately. Six of the trials (20%) described a standardized method for obtaining and documenting ADE information. Only three studies utilized an independent safety monitoring committee to ensure thorough, unbiased assessment of adverse event reports. Based on their assessment, the authors recommend significant changes in antiepileptic study design to improve safety monitoring and ADE reporting. Anderson M, Choonara I. A systematic review of safety monitoring and drug toxicity in published randomized controlled trials of antiepileptic drugs in children over a 10-year period. Arch Dis Child 2010; (epub ahead of print).

Guillain-barré Syndrome After H1cn1 Vaccine

Tremblay and colleagues describe a case of Guillain-Barré Syndrome (GBS) in an 11-year-old boy after administration of the H1N1 vaccine during the fall of 2009. The patient presented to the hospital with facial diplegia, abdominal, forehead, neck, and thigh pain 13 days after receiving a subcutaneous injection of the Arepanrix® H1N1 vaccine. Neurologic examination demonstrated symmetric paralysis of the eighth cranial nerve, along with proximal weakness of the shoulder and pelvis. After exclusion of alternative diagnoses and further investigation, the authors concluded that there was a probable relationship between the patient’s condition and the vaccine. While the CDC reports only 12 probable cases of GBS from approximately 46 million doses of vaccine administered during 2009 (MMWR 2009;58:1–6), this case serves as a reminder of the potential for this condition in children. Tremblay M, Closon A, D’Anjou G, et al. Guillain-Barré syndrome following H1N1 immunization in a pediatric patient. Ann Pharmacother 2010;44:1330–3.

 

Valproate-induced Metabolic Effects

Long-term use of valproate has long been associated with the potential for weight gain and insulin resistance in children with epilepsy. A two part study was recently conducted to address the mechanism for these adverse effects. The first part, a cross-sectional study of children previously diagnosed with epilepsy was designed to evaluate insulin sensitivity and weight gain. Patients were divided into 3 groups: those who had not yet received valproate, patients currently receiving treatment, and those who had discontinued valproate at least 1 year previously. The second part of the study was a prospective longitudinal follow-up of the children in the first group after they began treatment with valproate. Sixty children were enrolled, with 20 continuing on to the longitudinal portion of the study.

When the children were divided into the 3 groups, there were no differences in age, or baseline glucose and insulin levels. There were, however, significant differences in body mass index (BMI) and measurements of insulin resistance. The group currently receiving valproate had a significantly higher BMI than the group who had not been treated (20.22±4.11 compared to 15.97±1.70, p = 0.0002). There was also higher insulin resistance in this group (1.67±1.08 versus 1.04±0.38, p = 0.003). No differences were found between the treatment group and those who had discontinued valproate. Significant correlations were found in the treatment group between the daily valproate dose and both insulin resistance (r = 0.663) and fasting insulin levels (r = 0.765). The longitudinal study revealed significant increases in fasting and post-glucose challenge insulin values at the one year follow-up, however the degree of insulin resistance eventually leveled off over time. The information gained from this study suggests a need for routine monitoring of weight and blood glucose values in children receiving long-term treatment.Masuccio F, Verrotti A, Chiavaroli V, et al. Weight gain and insulin resistance in children treated with valproate: the influence of time. J Child Neurol 2010; 25:941–7.

 

Fonte: Medscape Pharmacist

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