Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A obesidade mÃrbida à uma doenÃa muito freqÃente nos dias de hoje. O paciente obeso mÃrbido apresenta importantes alteraÃÃes fisiolÃgicas e anatÃmicas, alÃm de comorbidades de grande significado clÃnico, particularmente cardiovasculares, respiratÃrias e metabÃlicas, exigindo do mÃdico anestesiologista pleno conhecimento dessas peculiaridades, para que possa realizar uma abordagem segura, tendo em vista que os procedimentos cirÃrgicos tÃm sido cada vez mais constantes nesse grupo de indivÃduos. O objetivo deste estudo clÃnico, prospectivo e nÃo aleatÃrio, foi avaliar os efeitos da administraÃÃo do agente agonista &#945;2 adrenÃrgico clonidina, como fÃrmaco coadjuvante de tÃcnica anestÃsica padronizada para cirurgia da obesidade em 36 pacientes que pertenciam ao grupo de obesidade mÃrbida do Hospital UniversitÃrio Walter CantÃdio. Foram distribuÃdos em dois grupos: o primeiro grupo composto por 25 pacientes recebeu clonidina administrada em infusÃo contÃnua na dose de 2 mcg/kg de peso ideal, iniciada dez minutos antes da induÃÃo anestÃsica e mantida em seguida, na dose de 0,4 a 0,7 mcg/kg/h de peso ideal, tendo sido descontinuada no inÃcio do fechamento da aponeurose; o segundo grupo composto por 11 pacientes, nÃo recebeu a infusÃo do agente agonista, entretanto todo o restante da tÃcnica anestÃsica foi igual. As principais variÃveis avaliadas foram a pressÃo arterial sistÃlica e diastÃlica, a freqÃÃncia cardÃaca, o Ãndice bispectral (BIS), a concentraÃÃo expirada de sevoflurano (CESEV), a sensaÃÃo de dor, o mini-exame do estado mental (MEEM) e os nÃveis glicÃmicos. Quanto aos dados demogrÃficos, nÃo houve diferenÃa entre os dois grupos estudados. Com relaÃÃo aos parÃmetros hemodinÃmicos, houve aumento da pressÃo sistÃlica e diastÃlica no momento da incisÃo cirÃrgica no grupo controle (P < 0,05). NÃo houve diferenÃa na funÃÃo cognitiva. Foi verificada uma melhor analgesia pÃs-operatÃria no grupo clonidina (P< 0,05). NÃo houve diferenÃa significativa no comportamento glicÃmico no perÃodo peri-operatÃrio quando foram analisados os dois grupos, porÃm quando se analisou apenas os pacientes do grupo clonidina, observou-se que nos nÃo diabÃticos, ocorreu um aumento significativo da glicemia durante o perÃodo intra-operatÃrio (P < 0,05), no entanto, sem ultrapassar o valor de 200 mg/dl. Houve maior controle hemodinÃmico intra-operatÃrio com a utilizaÃÃo da clonidina. O grupo clonidina apresentou um despertar mais rÃpido ao final da cirurgia e tambÃm obteve melhor analgesia no perÃodo pÃs-operatÃrio. O uso do fÃrmaco nÃo interferiu com o retorno das funÃÃes cognitivas. Em baixas doses, a clonidina nÃo determinou alteraÃÃes nos nÃveis glicÃmicos no perÃodo peri-operatÃrio, entretanto, nos pacientes diabÃticos em que o agonista foi administrado, observou-se um melhor controle da glicemia, o que nÃo foi demonstrado nos pacientes nÃo diabÃticos. Os pacientes dos dois grupos nÃo apresentaram efeitos adversos. / Morbid obesity is very frequent nowadays. The morbidly obese patient presents important anatomical and physiological changes, and comorbidities of great clinical significance, particularly cardiovascular, respiratory and metabolic demands of the physician anesthesiologist must be aware of these peculiarities, so you can make a safe approach, considering that the surgical procedures have been increasingly appearing in this group of individuals. The objective of this clinical, prospective and not randomized, was to evaluate the effects of administration of the &#945;2-adrenergic agonist clonidine as an adjunct to drug standardized anesthetic technique for obesity surgery in 36 patients who belonged to the group of morbid obesity at the university hospital . Were divided into two groups: the first group of 25 patients received clonidine administered by continuous infusion at a dose of 2 mcg / kg ideal body weight, which started ten minutes before induction of anesthesia and then maintained at a dose from 0,4 to 0,7 mcg / kg / h of ideal weight, having been discontinued in the early closure of the aponeurosis and the second group of 11 patients did not receive the infusion of the agonist, however the rest of the anesthetic technique was equal. The main variables evaluated were systolic and diastolic blood pressure, heart rate, bispectral index (BIS), the expired concentration of sevoflurane, pain sensation, the mini-mental state examination (MMSE) and levels glucose. With regard to demographics, there was no difference between the two groups. With respect to hemodynamic parameters, an increase of systolic and diastolic blood pressure at the time of surgical incision in the control group (P <0.05). There was no difference in cognitive function. It was observed a better postoperative analgesia in the clonidine group (P <0.05). There was no significant difference in glycemic levels in the peri-operative when they examined the two groups, but when we examined only patients in the clonidine group, we observed that in nondiabetic patients, there was a significant increase in blood glucose during the intraoperative (P <0.05), however, not to exceed 200 mg / dl. There was greater intraoperative hemodynamic control with the use of clonidine. The clonidine group showed a more rapid awakening at surgery and also achieved better analgesia in the postoperative period. The use of the drug did not interfere with the recovery of cognitive function. At low doses, clonidine did not cause changes in glucose levels in the perioperative period, however, in diabetic patients in which the agonist was administered, there was a better glucose control, which was not demonstrated in nondiabetic patients. Patients in both groups showed no adverse effects.

During a finite developmental phase – the brain growth spurt – the brain grows and matures at an accelerated rate. During this period the brain is more sensitive to harmful substances such as ethanol and environmental toxins than before or after. This period extends from the last trimester to the second year in humans and occurs postnatally in the mice used for these studies. The aims of this thesis were; to investigate common anaesthetics ability to promote acute apoptosis and late persistant behavioural aberrations measured with spontaneous behaviour in a novel home environment, learning in a radial arm maze and anxiety-like behaviour in an elevated plus maze, to measure alterations in BDNF, CaMKII, GAP-43, synaptophysin and tau after anaesthesia exposure, to evaluate clonidine as a potentially protecting agent and examine if theophylline, a chemically unrelated compound, causes similar effects as anaesthetics. Some of the results are: combinations of anaesthetics acting on the GABAA receptor (propofol or pentothal) and NMDA receptor (ketamine) exhibit more apoptosis and behavioural alterations than single anaesthetics. Ketamine, but not propofol, alters the content of CaMKII and GAP-43 proteins important in brain development. Propofol exposure alters the content of BDNF (brain derived neurotrophic factor) in hippocampus, frontal and parietal cortex. Neonatal propofol exposure leads to less sensitiveness to diazepam in adult age as measured with induced spontaneous behaviour and an elevated plus maze. Clonidine, an alpha2 adrenergic agonist does not cause any aberrations and appears to prevent apoptosis and behavioural alterations after ketamine. Theophylline, used as apnoea treatment in neonates, also increases apoptosis and alters normal behaviour. Thus, alterations both in neuronal survival, function and protein expression is apparent after neonatal exposure to anaesthetics. This is also shown in studies of Rhesus monkeys. However, it is still difficult to assess how these findings should extrapolate to humans. Epidemiological studies give conflicting results. Insufficient anaesthesia is not a solution as pain and stress cause even more pronounced problems. Minimizing anaesthetic exposure, delaying procedures until after the sensitive phase and finding protective agents, such as clonidine, are possible strategies. Evaluation of other substances that infants are exposed to is needed.

Made available in DSpace on 2014-06-11T19:30:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-22Bitstream added on 2014-06-13T19:19:21Z : No. of bitstreams: 1 rocha_apc_dr_botfm.pdf: 1024893 bytes, checksum: 0e64a9e23240bce6205f3161a978ae84 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A sedação para a realização de cateterismo cardíaco, apesar de pouco estudada, tem sido alvo de preocupação de alguns anestesiologistas. Os benzodiazepínicos, os agonistas alfa-2 adrenérgicos e os opióides são comumente utilizados para este fim, entretanto, cada um destes medicamentos possui vantagens e desvantagens. O objetivo deste trabalho é avaliar a eficácia do sufentanil e da clonidina como medicação sedativa em pacientes submetidos a cateterismo cardíaco, comparando o impacto dos mesmos sobre os parâmetros hemodinâmicos e respiratórios apresentados, observando a presença de efeitos colaterais, além da satisfação do paciente e do hemodinamicista durante o exame. Trata-se de um ensaio clínico prospectivo, duplo-cego, randomizado e controlado, que envolveu sessenta pacientes divididos igualmente em dois grupos: GS e GC que receberam respectivamente, 0,1 mcg/kg de sufentanil e 0,5 mcg/kg de clonidina. Estes fármacos foram administrados antes da realização do cateterismo cardíaco. O escore de sedação segundo a escala de Ramsay, a necessidade de utilização de midazolam, os efeitos colaterais, a PAS, a PAD, a FC, a FR e a SpO2 foram registrados a cada cinco minutos, sendo os dados analisados em 06 diferentes momentos. Os grupos foram homogêneos em relação aos dados demográficos e avaliação clínica inicial. O comportamento da PAS, da PAD, da FC e da FR foi semelhante nos dois grupos, entretanto os pacientes do GS apresentaram menor escore de sedação segundo a escala de Ramsay no momento 2 e SpO2 menor que o GC no momento 6. Os pacientes do GS apresentaram maior incidência de NVPO que os pacientes do GC. A satisfação dos pacientes foi maior no GC. Os hemodinamicistas mostraram-se igualmente satisfeitos nos dois grupos. O sufentanil e a clonidina se mostraram efetivos como fármacos sedativos em pacientes submetidos a cateterismo cardíaco. / Sedation for cardiac catheterization, although not largely studied, has worried a number of anesthesiologists presently. Not only benzodiazepinic medicine, but also alpha- 2 adrenergic agonist and opioids are commonly used drugs to this end. Each one of these medicaments presents a series of advantages as well as disadvantages. The objective of this paper is to evaluate the effectiveness of sufentanil and clonidine as a sedative medicament to patients submitted to cardiac catheterization, comparing their impact over the hemodynamic and respiratory parameters witnessed, observing the occurrence of side effects, besides patient’s and hemodynamicist’s satisfaction during the examination. This consists of a prospective, double-blinded, randomized and controlled clinical essay, which involved sixty patients equally divided in two different groups: GS and GC, who, respectively, received 0,1mcg/kg of sufentanil and 0,5 mcg/kg of clonidine. Both administered before cardiac catheterization. The sedation score, according to Ramsay’s scale, the necessity of utilizing midazolam, side effects, SAP, DAP, CF and SpO2 were registered every five minutes and data analyzed in six different moments. The studied groups were homogeneous regarding demographic data and initial clinical evaluation. The behavior of SAP, DAP, CF and RF was similar in both groups. However, a lower sedation score regarding Ramsay’s scale was observed in GS patients at moment 2 and at moment 6 SpO2 was found to be lower than GC. All GS patients seemed to have had higher incidence of PONV compared to GC patients. Considering patients’ satisfaction, it was higher in GC. Hemodynamicists seemed equally satisfied in both groups. Sufentanil and clonidine seemed to have been more effective as sedative medicaments in patients submitted to cardiac catheterization.

Orientador: Marcio de Moraes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-08T11:47:59Z (GMT). No. of bitstreams: 1 Farah_GustavoJacobucci_D.pdf: 4741739 bytes, checksum: aa9a8e42479f6099d0d66162d83a1c1c (MD5) Previous issue date: 2007 / Resumo: Hipotensão induzida ou controlada nos procedimentos em Cirurgia e Traumatologia Buco-Maxilo-Faciais é um método pelo qual a pressão arterial é diminuída de maneira previsível e deliberada. Por se tratar de cirurgias invasivas e com considerável potencial de sangramento trans-operatório, são necessárias algumas manobras anestésicas e cirúrgicas para se evitar intercorrências no ato operatório. Com a finalidade de diminuir o sangramento e a duração das cirurgias e proporcionar um melhor campo operatório são empregadas técnicas de hipotensão induzida. O propósito deste estudo foi comparar dois protocolos farmacológicos de hipotensão induzida em pacientes submetidos à cirurgia ortognática, avaliando a resposta fisiológica e estabilidade hemodinâmica no trans e pósoperatório. Participaram do estudo 20 pacientes ASA I, na faixa etária de 17 e 44 anos, que apresentavam deformidades dento-esqueléticas, divididos em dois grupos: grupo I (clonidina associada ao remifentanil), e grupo II (dexmedetomidina associada ao isoflurano), além de drogas comuns a ambos os grupos. Foram avaliadas respostas como pressão arterial, freqüência cardíaca, temperatura no trans e pós-operatório, incidência de náuseas / vÃ'mitos, dor pós-operatória, tempo de despertar, de extubação e de recuperação pós-anestésica. Verificou-se, por meio de análise estatística utilizando o teste de Medidas Repetidas, que não houve diferença significativa entre os grupos com relação às respostas fisiológicas e para a duração das cirurgias. Conclui-se que a hipotensão arterial induzida é uma técnica que pode ser adotada em cirurgias ortognáticas de maior duração de tempo e com expectitativa de muito sangramento. Além disso, ambos os protocolos estudados são eficazes e seguros para a anestesia hipotensiva, devendo ser escolhidos com base nas relações de risco e custo/benefício / Abstract: Induced or controlled hypotension in Oral and Maxillofacial Surgery is a method by which blood pressure is reduced in a safe and deliberate way. This invasive type of surgery and has a high probability of intraoperative blood loss. Thus, certain anesthetic and surgical procedures are necessary to avoid complications during surgery. Induced or controlled hypotension techniques are used to reduce surgery time and intraoperative blood loss, and to provide a better operating environment. The purpose of this study was to compare two induced hypotension pharmacological protocols in patients undergoing orthognathic surgery and to avaluate physiological response and haemodynamic stability in the intra and postoperative periods. Twenty patients (ASA I), between the ages of 17 and 44, who had skeletal and dental deformities were divided into two groups: in group I, clonidine associated to remifentanil, was used as the hypotensive medication; and in group II, dexmedetomidina associated to isoflurane was used, in addition to other drugs that were used in both groups. Blood pressure, heart frequency, temperature intra and postoperative, incidence of nausea and vomiting, postoperative pain and waking, extubation and postanesthetic recovery times were analyzed. Through statistical analysis using the Repeated Measures test, it was verified that there were no significant differences between the groups regarding physiological responses or surgery time. It was concluded that induced hypotension is a technique that can be adopted in orthognathic surgeries of long duration with the expectation of great blood loss. Furthermore, both of the protocols studied were efficient and safe for use in hypotensive anesthesia, and should be chosen based on the risk and cost to benefit ratio / Doutorado / Cirurgia e Traumatologia Buco-Maxilo-Faciais / Doutor em Clínica Odontológica

Summary: The effects of clonidine, a central alpha2 agonist, on changes in blood pressure caused by muscle afferent nerve (ergoreceptor) activation and baroreceptor manipulation were studied in cats. Prolonged isometric contractions (ergoreceptor activation) of the gastrocnemius and plantaris muscles increased mean arterial pressure by 53 mmHg. This pressor response was not altered by naloxone (0.5 μmol·litre-1) but was eliminated by clonidine (0.5-2.0 μg) when injected into the cerebral aqueduct. Brief occlusion of the carotid artery (15-30 s) caused mean arterial pressure to increase by 32-42 mmHg at rest. Neither naloxone nor clonidine altered the magnitude of the reflex pressor response to carotid occlusion. Similar increases in pressure were measured when occlusion was applied during fatiguing isometric contractions; thus baroreceptor induced increases in pressure were superimposed on the ergoreceptor induced blood pressure changes. Naloxone did not affect the changes in pressure caused by either reflex response. Clonidine continued to eliminate the pressor response to muscular contraction but did not affect the pressure increase when the carotid occlusion was applied during contractions. Electrical stimulation of the carotid sinus nerve caused blood pressure to decrease by 36 mmHg during rest and by 41 mmHg during fatiguing isometric contractions. Clonidine did not alter the depressor response to carotid sinus nerve stimulation. These data may indicate that separate pathways centrally mediate the changes in blood pressure caused by ergoreceptor and baroreceptor afferent activation. The integration of the ergoreceptor pathway may involve a catecholaminergic-opioidergic system but the present results do not suggest a similar interaction for the baroreceptor integration.

The ability of derivatives of 2-aminotetralins (2AT), cis- or trans-isomers of octahydrobenzo[f]quinolines (BfQ) and clonidine to modulate acetylcholine release was studied using field-stimulated guinea pig ilea (GPI). Antihistaminic and antiacetylcholine activities were also determined using isolated superfused segments of GPI. Hydroxylated 2AT, BfQ and clonidine inhibited field stimulation-induced contractions through α-adrenoceptor mechanisms which were antagonized by phentolamine. In contrast, the inhibition produced by nonhydroxylated 2AT was not attenuated by α-adrenoceptor antagonism. 2AT, trans-7,8-dihydro-BfQ and cis-8,9-dihydroxy-BfQ inhibited contractions induced by nicotine bitartrate using superfused GPI. Clonidine was inactive as an antinicotinic agent and there was no correlation between a compound's ability to inhibit contractions induced by field stimulation and its antinicotinic activity. Various 2AT derivatives demonstrated weak antimuscarinic and/or antihistaminic activities on superfused ileal segments. These data demonstrate that these agents posses a spectrum of pharmacological activity.

No description available.

L’arthrose et l’arthrite rhumatoïde sont deux pathologies articulaires caractérisées par la dégradation du cartilage articulaire, subséquente à la production de divers médiateurs inflammatoires. Le traitement de ces pathologies se limite généralement à soulager le patient des épisodes douloureux et inflammatoires et à améliorer sa qualité de vie. Dans le cas de l’arthrose, peu de traitements permettent d’enrayer significativement l’évolution de la dégradation du cartilage et donc de la maladie. Par contre, l’arthrite rhumatoïde peut être efficacement ralentie grâce à l’administration de certaines molécules. Néanmoins, ces traitements n’ont généralement montré qu’une efficacité à court-terme, requérant une administration fréquente. L’objectif de ce travail repose donc sur l’élaboration de nouvelles options thérapeutiques permettant de réduire la fréquence d’administration ainsi que les effets indésirables des traitements actuels. La délivrance de molécules en intra-articulaire associée à une libération prolongée offre l’avantage d’exposer les sites directement impliqués dans l’évolution de la maladie à une ou plusieurs molécules efficaces contre l’inflammation et la douleur, et aidant à la régénération du cartilage, durant plusieurs semaines, voire des mois.<p>Des microparticules de PLGA chargées en clonidine ou en bétaméthasone ont donc été optimisées afin d’obtenir des efficacités d’encapsulation appréciables (clonidine HCl :EE ≈ 20% ;dipropionate de bétaméthasone :EE ≈ 70%), une taille adaptée à l’administration intra-articulaire (12 – 38 µm) et une libération de la molécule s’échelonnant sur 5 à 8 semaines. La libération prolongée de la clonidine implique des mécanismes de diffusion de la molécule ainsi que de dégradation/érosion du polymère. Au vu de l’absence de réaction inflammatoire, les microparticules développées sont correctement tolérées par les chondrocytes, synoviocytes, PBMC et neutrophiles, principales cellules impliquées dans les mécanismes inflammatoires de l’arthrose et de l’arthrite rhumatoïde. L’évaluation de l’efficacité anti-inflammatoire des microparticules vides et chargées en clonidine ou en bétaméthasone via l’étude de l’expression et de la sécrétion de différents médiateurs de l’inflammation a permis d’aboutir à plusieurs conclusions :(i) les microparticules vides sont associées à un effet anti-inflammatoire, (ii) les microparticules chargées en clonidine n’ont pas montré d’activité anti-inflammatoire propre pouvant être attribuée à la clonidine, et (iii) les microparticules de bétaméthasone ont confirmé l’effet anti-inflammatoire de la bétaméthasone. Enfin, l’étude de la toxicité des principes actifs et microparticules vides ou chargées a montré une toxicité significative de la clonidine sur les synoviocytes. Néanmoins, l’encapsulation des principes actifs dans les microparticules de PLGA a permis d’éliminer cette toxicité, protégeant donc efficacement les cellules articulaires.<p>Les microparticules développées permettent alors d’envisager l’encapsulation d’autres molécules anti-inflammatoires ou une combinaison de molécules ayant des effets complémentaires (anti-inflammatoire et antidouleur). L’utilisation de la clonidine dans ces indications devra être réévaluée en étudiant de façon approfondie son efficacité dans la douleur. / Both osteoarthritis and rheumatoid arthritis are articular diseases characterized by the degeneration of the joint cartilage, resulting from the production of various inflammatory mediators. The current treatment of these diseases is restricted to alleviate the painful and inflammatory episodes of the patients and to improve its quality of life. In osteoarthritic patients, few treatments allow to significantly stop the evolution of the degradation of the cartilage and, consequently, the disease. In rheumatoid arthritis, the evolution can be slowed down following the administration of some drugs. Nevertheless, these treatments are often associated to a short-term efficacy. The objective of this work is to develop new therapeutic options that allow to reduce the frequency of administration and the side effects of the current treatments. The intraarticular delivery combined to controlled-release presents the advantage to expose the sites directly involved in the evolution of the disease to one or more molecules effective to relieve the pain, inflammation and to help the regeneration of the cartilage.<p>Clonidine or betamethasone-loaded PLGA microparticles were optimized to reach suitable encapsulation efficiencies (clonidine HCl: EE ≈ 20%; betamethasone dipropionate: EE ≈ 70%), an appropriate size for an intraarticular delivery (12 – 38 µm) and a controlled-release of the molecule over 5 to 8 weeks. The release of clonidine implies mechanisms of diffusion and degradation/erosion of the polymer. Given the absence of an inflammatory reaction, the developed microparticles were properly tolerated by the chondrocytes, synoviocytes, PMBC and neutrophils, which are the main cells involved in the inflammatory reaction of osteoarthritis and rheumatoid arthritis. The assessment of the anti-inflammatory efficacy of the drug-free and drug-loaded microparticles through the evaluation of the expression and the secretion of various inflammatory mediators allowed to draw several conclusions: (i) drug-free microparticles were associated to an anti-inflammatory effect, (ii) clonidine-loaded microparticles did not show any anti-inflammatory activity that could be attributed to clonidine, and (iii) betamethasone- loaded microparticles confirmed the anti-inflammatory effect of betamethasone. Finally, the evaluation of the toxicity of the drugs and microparticles showed a significant toxicity of clonidine against synoviocytes. Nevertheless, the encapsulation of the drugs in PLGA microparticles induced the suppression of this toxicity, protecting in this way the articular cells. <p>Entrapping other anti-inflammatory molecules or a combination of molecules with complementary effects (anti-inflammatory and anti-nociceptive drugs) in the PLGA microparticles developed has to be considered. Moreover, the use of clonidine in these indications has to be reassessed by a thorough study of its anti-nociceptive potential.<p><p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Le manque de produits pharmaceutiques destinés à la population pédiatrique est un problème auquel sont confrontés les professionnels de la santé. Les pharmaciens doivent fréquemment se tourner vers les médicaments destinés aux adultes afin de fournir aux jeunes patients les traitements adéquats. L’utilisation de préparations magistrales pour adapter les médicaments homologués aux besoins de la population pédiatrique reste, encore à ce jour, l’option la plus souvent utilisée. Dans ce mémoire, nous proposons le développement et l’évaluation de nouvelles formulations pharmaceutiques destinées à la population pédiatrique afin de bonifier les options thérapeutiques mises à la disposition des professionnels de la santé. De plus, nous avons exploré l’utilisation de nouvelles techniques spécialisées pour surmonter des défis analytiques rencontrés, ultimement dans le but de déterminer en toute confiance la stabilité et la sécurité de ces nouvelles formulations. La première étude visait à évaluer la stabilité de préparations magistrales de chlorhydrate de clonidine (20 µg/mL) préparées avec des comprimés dans le véhicule commercial Ora-Blend. Les formulations embouteillées ont été conservées à 25°C/60% RH pendant 90 jours. Les défis analytiques rencontrés lors de l’analyse de la stabilité chimique ont été surmontés par l’implémentation d'une nouvelle méthode d'extraction en phase solide, ayant permis d’optimiser la quantification du chlorhydrate de clonidine, se retrouvant qu’en très faible quantité dans les formulations orales. L'absence d'instabilités physiques, évaluée par des mesures qualitatives et quantitatives, et l’absence d'instabilités chimiques, mise en évidence par une méthode HPLC-UV indicatrice de stabilité, confirment qu’accorder une date de péremption de 90 jours à ces préparations magistrales serait approprié. La deuxième étude portait sur l’évaluation de la stabilité de préparations magistrales d’hydroxyurée (100 mg/mL) dans l’Ora-Blend. Dans le cadre de cette étude, différentes méthodes de préparation (mortier, mélangeur, QuartetRx) et différentes sources de principe actifs (poudre, contenu des capsules, capsules entières) ont été étudiées. Toutes les formulations ont été conservées à 25°C pendant 90 jours dans des bouteilles et 14 jours dans des seringues orales. Le développement d'une méthode HPLC indicatrice de stabilité impliquant la dérivation de l’hydroxyurée par le xanthydrol aura permis la rétention l’hydroxyurée sur une colonne à phase inverse de type C18. Plus de 90.0 % de la concentration initiale d’hydroxyurée a été conservé tout au long de l’étude, et ce, pour toutes les conditions testées. L’évaluation visuelle des préparations n’a révélé aucun changement au cours de l’étude de stabilité. Des changements de pH allant jusqu'à 1.6 unités ont toutefois été observés après 90 jours d’entreposage et ont mis en lumière une voie de dégradation de l’hydroxyurée, générant ultimement l’ion ammonium. Ce dernier a été quantifié et les concentrations mesurées, définies comme acceptables. Les résultats ont montré que toutes les formulations d’hydroxyurée étudiées sont demeurées stables jusqu’à 90 jours à 25°C. Pour terminer, une étude exploratoire ayant pour but d’évaluer des comprimés à croquer à saveur d’érable a été réalisée. Le sucre d’érable et un arôme naturel d’érable ont été ajoutés à la composition des comprimés afin d’obtenir une saveur suffisamment prononcée pour masquer le goût amer de l’acétaminophène. Une étude de stabilité préliminaire, impliquant une période de 30 jours d’entreposage dans des conditions de stabilité accélérées (40°C/75%RH), aura permis d’explorer les propriétés physico-chimiques de cette nouvelle formulation, de soulever les défis potentiels et de générer des hypothèses en lien avec l’augmentation de dureté observée après seulement 14 jours d’entreposage. Les résultats de cette étude préliminaire serviront de point de départ pour le futur développement de produits pharmaceutiques à la saveur du Québec. Les techniques utilisées et les études réalisées dans le cadre de ce projet de maîtrise auront permis de générer des résultats robustes qui pourront être utilisés par les professionnels de la santé. Ces informations seront pertinentes à la pratique pharmaceutique et permettront d’offrir à la population pédiatrique des nouvelles options de traitement sécuritaires et efficaces. / The lack of pharmaceuticals intended to the pediatric population is an issue facing healthcare professionals. Pharmacists must frequently resort to adult treatments to provide adequate treatment to young patients. The use of compounding to adapt commercial drugs to the needs of the pediatric population is still, to this day, the most considered option. In this master’s thesis, we propose the development and evaluation of new medicinal preparations for pediatrics in order to improve and diversify the therapeutic options available to healthcare professionals. In addition, we have explored the use of new specialized techniques to overcome analytical challenges encountered, with the goal of confidently determining the stability and safety of these new formulations. The first study aimed to assess the stability of compound preparations of clonidine hydrochloride (20 µg / mL) prepared with tablets in the commercial vehicle Ora-Blend. Bottled formulations were stored at 25°C/60% RH for 90 days. The analytical challenges encountered during the analysis of chemical stability were overcome by the implementation of a new method of solid phase extraction, which allowed to optimize the quantification of clonidine hydrochloride, present in very small amount in oral formulations. The absence of physical instabilities, assessed by qualitative and quantitative measurements, and the absence of chemical instabilities, as demonstrated by a stability indicating HPLC-UV method, confirm that it would be appropriate to grant a 90-day expiration date to these compounded oral liquids. The second study evaluated the stability of compound preparations of hydroxyurea (100 mg / mL) in Ora-Blend. In this study, different preparation methods (mortar, mixer, QuartetRx) and different sources of hydroxyurea (powder, content of capsules, whole capsules) were studied. All formulations were stored at 25°C for 90 days in bottles and 14 days in oral syringes. The development of a stability indicating HPLC method involving the derivatization of hydroxyurea by xanthydrol will have enabled hydroxyurea retention on a C18 type reverse phase column. Over 90.0% of the initial hydroxyurea concentration was recovered throughout the study under all conditions tested. Visual evaluation of the preparations did not reveal any changes during the stability study. Changes in pH of up to 1.6 units were observed after 90 days of storage and revealed a degradation pathway for hydroxyurea, ultimately generating ammonium ion. The latter was quantified, and the measured concentrations defined as acceptable. The results showed that all hydroxyurea formulations studied were stable for up to 90 days at 25°C. Finally, an exploratory study to evaluate maple flavored chewable tablets was carried out. Maple sugar and a natural maple flavor have been added to the composition of the tablets to achieve a flavor strong enough to mask the bitter taste of acetaminophen. The pre-stability study, involving a period of 30 days of storage under accelerated stability conditions (40°C/75% RH), will have made it possible to explore the physicochemical properties of this new formulation, to raise the potential challenges and generate hypotheses related to the increase in hardness observed after only 14 days of storage. The results of this preliminary study will serve as a starting point for the future development of pharmaceutical products with a Quebec flavor. The techniques used and the studies performed will have generated robust results that could help healthcare professionals in their practice.