Pharmacovigilance and the safety of veterinary medicinal products

Dissertação de Mestrado Integrado em Medicina VeterináriaPharmacovigilance in veterinary medicine has developed considerably in the recent years. The increase in legislation in the area of veterinary medicinal products, as well as the increased awareness of the veterinarian regarding the need to report the adverse events observed during the use of the medicines in the animals in his care, has led to an increase in the number of cases reported at European level. For the preparation of this master's dissertation, a review was made of the existing published references on the subject of pharmacovigilance, namely the legal framework, the requirements for the marketing authorization holder of the veterinary medicinal product as well as for the veterinarian prescribing the medicines to the animals which are under her/his responsibility and treatment. Signal management is currently considered the best way to carry out drug surveillance and it follows a specific methodology. Signal management is the pillar of the future legislation on veterinary medicinal products as well as human medicines. In this study the European pharmacovigilance systems, France, Portugal, Spain, UK, are analysed and compared because although having the same legislative frame, each one has different particularities. There is also a reflection about the underreporting of adverse events by veterinarians and some measures that can improve notification, such as use of new technologies and improvement in the feedback to reporter, among others. Whether as a clinician, as veterinarian working in the pharmaceutical industry as well as in the competent authorities, the veterinary professional is essential in the veterinary pharmacovigilance system, the continuous monitoring of veterinary medicinal products, maintaining the positive benefit-risk balance and in the protection of animal health and food safety.RESUMO - Farmacovigilância e a segurança dos medicamentos veterinários - A farmacovigilância em medicina veterinária tem-se desenvolvido bastante nos últimos anos. O aumento de legislação na área do medicamento veterinário, bem como a maior sensibilização do médico veterinário para a necessidade de reportar os eventos adversos observados aquando da utilização do medicamento veterinário nos animais que estão a seu cuidado, têm resultado num aumento no número de casos reportados a nível europeu. Para a elaboração desta dissertação de mestrado foi feita uma revisão das publicações existentes sobre o assunto da farmacovigilância nomeadamente o enquadramento legal, os requisitos para o titular de autorização de introdução no mercado do medicamento veterinário, bem como para o médico veterinário que prescreve os medicamentos aos animais que tem sob sua responsabilidade e tratamento. Atualmente considera-se que a gestão de sinais é a melhor forma para realizar a vigilância dos medicamentos e esta segue uma metodologia específica. A gestão de sinais dos eventos adversos é o pilar da futura legislação quer do medicamento veterinário, quer do medicamento de uso humano. Neste estudo os sistemas de farmacovigilância europeus, como de Espanha, França, Portugal e Reino Unido, são analisados e comparados, pois tendo como base a mesma moldura legislativa europeia, cada um deles tem as suas particularidades. Também se faz uma reflexão sobre a subnotificação de eventos adversos por parte dos veterinários e algumas medidas que podem melhorar a notificação, como a utilização das novas tecnologias e uma melhoria nas respostas que se dão aos notificantes, entre outras. Seja como médico veterinário clínico, como médico veterinário profissional do sector farmacêutico, bem como membro nas autoridades competentes, a figura do médico veterinário é fundamental no sistema de farmacovigilância veterinária, na monitorização contínua dos medicamentos veterinários, na manutenção do benefício-risco positivo e na proteção da saúde animal e segurança alimentar.N/

A homeopatia para os animais.

bitstream/item/65416/1/COT-46-A-homeopatia-para-os-animais.pd

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbra

Otimização e validação de metodologia para determinação de Ivermectina em amostras de leite

Dissertação (mestrado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Tecnologias Química e Biológica, 2014.O fármaco veterinário endectocida conhecido como ivermectina ou 22,23-dihidroavermectina B1a + 22,23-dihidroavermectina B1b, apesar da sua recente proibição, continua a ser usado largamente no Brasil tanto em bovinos como em suíno e bubalino, porém a grande maioria se deve aos bovinos, devido ao fato do Brasil possuir o segundo maior rebanho mundial. A problemática da utilização deste fármaco está associada a uma possível excreção da ivermectina no leite desses animais, o qual é amplamente utilizado na dieta diária dos brasileiros, e os efeitos devido à exposição crônica a esse fármaco ainda não são bem estudados. Este trabalho adaptou uma metodologia para determinação da ivermectina em leite de bovinos. Foi realizada a validação da metodologia com leitura de amostra de leite fortificada. A amostra de leite integral foi coletada direto do animal para que permanecesse a quantidade total de gordura, devido ao caráter lipofílico do fármaco. O método validado baseou-se em cromatografia líquida com detecção UV/VIS. A extração foi realizada em duas partes, a primeira líquido-líquido, onde há a separação das gorduras e proteínas, e a segunda em fase sólida com o auxílio de cartuchos SPE C18. Para a leitura das amostras utilizou-se cromatógrafo líquido, com detector de UV-Vis, com coluna Phenomenex C18, 10cm, ID 46µm. Os resultados de validação mostraram que o método é linear, com coeficiente de determinação (R2) igual à 0,991, seletivo, preciso, com coeficientes de variação entre 3,98 e 9,42%, exato, com valores de recuperação variando entre 98 e 110% e com limites de detecção e quantificação de 19,825 µg/L e 49,350 µg/L respectivamente. _______________________________________________________________________________________________ ABSTRACTThe veterinary drug called ivermectin or endectocide 22.23-22.23-dihydroavermectin B1a + B1b dihydroavermectin, despite its recent ban, continues to be used widely in Brazil both in cattle and in pigs and buffalo, but the vast majority is due to cattle, due to the fact that Brazil has the second largest herd. The issue of use of this drug is associated with a possible excretion of ivermectin in milk of these animals, which is widely used in daily diet of Brazilians, and the effects due to chronic exposure to this drug are not well studied. This study adapted a method for determining the milk of bovine ivermectin. Validate the methodology with sample reading of fortified milk was performed. The sample of whole milk was collected directly from the animal to remain on the total amount of fat, due to the lipophilic nature of the drug. The validated method was based on liquid chromatography with UV detection / VIS. The extraction was performed in two parts, the first liquid-liquid, where there is a separation of fat and protein, and the second solid phase with the aid of C18 SPE cartridges. To read the samples we used liquid chromatography with UV-Vis detector with Phenomenex C18, 10cm, 46μm ID column. The validation results showed that the method is linear, with a coefficient of determination (R2) equal to 0.991, selective, precise, with coefficients of variation between 3.98 and 9.42%, exact, with recovery values ranging between 98 and and 110% limits of detection and quantification of 19,825 mg / L and 49,350 mg / l respectively

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Tissue Necrosis in Equine Associated with use of Phenylbutazone

Background: Wounds that occur with tissue necrosis and that result from the application of medications through the most diverse accesses are described as drug skin medical embolism or Nicholas syndrome in human medicine, with wide description. In veterinary medicine, this subject has not yet been described extensively and specifically in veterinary medicine, especially regarding to wounds that occurred after the application of non-intravenous medications in horses, even though these lesions are recurrent in the clinical routine.  This report aims to describe a case of skin necrosis in a horse, due to phenylbutazone infection. Case: A 7 year-old Mangalarga Marchador horse, weighing 400 kg, was admitted to the Veterinary Hospital for Large Animals of the Universiade Federal Rural do Rio de Janeiro (UFRRJ), with a history of phenylbutazone injection to the left side of the neck. The animal had an extensive wound on the neck and face on the left side and was characterized by the presence of cold and devitalized skin, with a hardened and parched appearance and that easily detached.  During the anamnesis, a single administration of 10 mL of a non-steroidal anti-inflammatory drug based on phenylbutazone was reported intramuscularly for about 10 days to control the pain resulting from the claudication present for 14 days. The medication was administered in the region of the lateral border of the neck, on the left side. After drug administration, the animal presented an increase in volume at the application site. After 24 h, the lesion spread from the inoculation region, extending to the head and chest of the animal. During debridement, it was found that the lesion did not reach the underlying muscle tissue. In addition to the wound, the animal had upper eyelid palsy, lower lip, and auricular ptosis. Treatment with surgical debridement of devitalized tissue, topical application of ozonated sunflower oil, ketanserin, and a free skin graft was instituted. During hospitalization, the animal had a corneal ulcer in the left eye with an unfavorable prognosis due to paralysis of the upper eyelid, with enucleation of the affected eyeball. The animal was under veterinary care for 180 days and was discharged when his wound was already in an advanced stage of healing. Discussion: The history of the application of phenylbutazone intramuscularly and the location and characteristics of the lesion presented by the patient in the present report suggest that this animal presented aseptic tissue necrosis resulting from the administration of non-steroidal anti-inflammatory drugs, phenylbutazone. Although aseptic tissue necrosis, better known as Nicolau's syndrome or drug embolism cutis, is widely characterized and described in this species, there are studies in the literature that reproduce the syndrome in pigs and rabbits. Phenylbutazone was able to cause arterial damage, mainly in the tunica intima of the artery in which the medication was administered, with perivascular inflammatory infiltrate and subsequent skin necrosis at the site of administration. In addition to the skin lesion, the animal started to show signs compatible with the left facial nerve lesion, evidenced by the immobility of the upper eyelid and labial and ear ptosis. This resulted in corneal ulceration and subsequent enucleation. The animal also developed chewing difficulty in the first months of hospitalization. This dysfunction may be due to a lesion of the mandibular nerve, responsible for innervating the masticatory muscles and the oral mucosa. However, the animal showed improvement in this aspect, no longer showing this condition after 90 days of hospitalization.  The treatment used was successful in healing the wound. Keywords: wound, tissue necrosis, iatrogenic injury, Nicolau Syndrome, treatment, horse. Título: Necrose tissular em equino associada ao uso de fenilbutazona. Descritores: ferida, necrose tecidual, iatrogenia medicamentosa, síndrome de Nicolau, tratamento, cavalo

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr