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Biomedicina Plano de Aula 3

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  • 1. Farmacologia Aula 3: Antidepressivos e estabilizadores do humor Professor: Caio Maximino Ementa: Depressão: Nosologia, diagnóstico e epidemiologia; Depressão: Patofisiologia; Alostasia e estresse; A teoria monoaminérgica da depressão; Neurofarmacologia da 5-HT; Corticoesteróides e depressão; Neurogênese e depressão; Marcadores bioquímicos da depressão: 5-H1AA, MHPG e CRH; Neuroimagem da depressão; Genética comportamental da depressão; Knock-out de receptores em modelos animais de depressão; Fármacos utilizados no tratamento da depressão: iMAOs, Tricíclicos, SSRIs, NaSSAs e NARIs; Eficácia dos antidepressivos; Outros tratamentos; Farmacocinética e farmacodinâmica dos antidepressivos; Farmacogenômica da depressão: Polimorfismos no gene 5-HTT e HTR1A; Tensão pré- menstrual e depressão perimenopausal; Transtorno bipolar: Nosologia, diagnóstico e epidemiologia; Transtorno bipolar: Patofisiologia; Genética comportamental do transtorno bipolar; Objetivos: Ao final da aula, os alunos devem ser capazes de 1) Definir o campo da farmacologia e os conceitos de droga, receptor e ligante, e interações entre esses construtos; 2) Conhecer e entender os aspectos qualitativos e quantitativos da interação ligante-receptor, em termos de agonistas e antagonistas; e 3) Conhecer e entender as bases fisiológicas da ação das drogas, especialmente no tocante a proteínas receptoras. Tarefa atribuída (Peso 0,6): Explicar, mecanisticamente, um mecanismo molecular de transdução de sinal (receptores ligados a canais, receptores acoplados à proteína G, receptores ligados à tirosina quinase e à guanilato ciclase, receptores nucleares). Formato: Esquema + legenda explicativa. Prazo de entrega: 14 de Abril. • Introdução 15 Exposição Apresentação da disciplina: ementa, métodos de avaliação, combinados práticos. min. dialogada • Desenvolvimento 75 Exposição Conceitos centrais: droga, receptor, afinidade e eficácia, interação ligante/receptor.
  • 2. • min. dialogada Alvos para a ação das drogas: Proteínas receptoras, canais iônicos, enzimas, moléculas transportadoras. • Farmacocinética I: Liberação e absorção • Conclusão 10 Exposição Fechamento: Atribuição de tarefa min. dialogada Bibliografia: Akiskal HS, McKinney WT (1973). Depressure disorders: Toward a unified hypothesis. Science 182: 20-29. Amat J et al. (2005). Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neuroscience 8: 365-371. Arias B et al. (2005). Evidence for a combined genetic effect of the 5-HT1A receptor and serotonin transporter genes in the clinical outcome of major depressive patients treated with citalopram. Journal of Psychopharmacology 19: 166-172. Benedetti F et al. (1999). Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar disorder. American Journal of Psychiatry 156: 1450-152. Bessa JM et al. (2008). The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Molecular Psychiatry El Yacoubi M et al. (2001). Adenosine A2A receptor antagonists are potential antidepressants: Evidence base don pharmacology and A2A receptor knock-out mice. British Journal of Pharmacology 134: 68-77. Green AR (2006). Neuropharmacology of 5-hydroxytryptamine. British Journal of Pharmacology 147: S145-S152. Guscott M et al. (2004). Genetic knockout and pharmacological blockade studies of the 5-HT7 receptor suggest therapeutic potential in depression. Neuropharmacology 48: 492-502.
  • 3. Haller J (2002). Behavioral responses to social stress in noradrenaline transporter knockout mice: Effects on social behavior and depression. Brain Research Bulletin 58: 279-284. Hayley S et al. (2005). Pathogenesis of clinical depression: Stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience 135: 659-678. Heisler LK et al. (1998). Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proceedings of the National Academy of Sciences USA 95: 15049-15054. Holmes A et al. (2003). Abnormal behavioral phenotypes of serotonin transporter knockout mice: Parallels with human anxiety and depression. Biological Psychiatry 54: 953-959. Jang KL (2005). The mood disorders. In: The Behavioral Genetics of Psychopathology: A Clinical Guide, pp. 67-86. Kaplan M (2004). Psychoanalysis and psychopharmacology: Art and science of combining paradigms. In: Panksepp J (ed.), Textbook of Biological Psychiatry, pp. 549-570. Hoboken: Wiley-Liss, Inc. Kendler KS et al. (2003). The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60: 929-937. Kim DK et al. (2000). Serotonin transporter gene polymorphism and antidepressant response. NeuroReport 11: 215-219. Korte SM et al. (2005). The Darwinian concept of stress: Benefits of allostasis and costs of allostatic load and the trade-offs in health and disease. Neuroscience and Biobehavioral Reviews 29: 3-38. MacQueen GM et al. (2001). Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behavioral Neuroscience 115: 1145-1153. Mayberg HS (2004). Depression: A neuropsychiatric perspective. In: Panksepp J (ed.), Textbook of Biological Psychiatry, pp.197-230. Hoboken: Wiley-Liss, Inc.
  • 4. Mayberg HS et al. (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45: 651-660. McEwen BS (2000). Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacology 22: 108-124. Meyer JH et al. (1999). Prefrontal cortex 5-HT2 receptors in depression: An [18F]setoperone PET imaging study. American Journal of Psychiatry 156: 1029-1034. Ridder S et al. (2005). Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. Journal of Neuroscience 25: 6243-6250. Rief W et al. (No prelo). Meta-analysis of the placebo response in antidepressant trials. Journal of Affective Disorders. Runinow DR, Schmidt PJ, Roca CA (1998). Estrogen-serotonin interactions: Implications for affective regulation. Biological Psychiatry 44: 839-850. Sánchez C, Meier E (1997). Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression: Are they all alike? Psychopharmacology 129: 197-205. Shaldubina A et al. (2001). The mechanism of lithium action: State of the art, ten years later. Progress in Neuro-Psychopharmacology and Biological Psychiatry 25: 855-866. Smeraldi E et al. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Molecular Psychiatry 3: 508-511. Yadid G et al. (2000). Elucidation of the neurobiology of depression: Insights from a novel genetic animal model. Progress in Neurobiology 62: 353-378.
  • 5. Este trabalho está licenciado sob uma Licença Creative Commons Atribuição-Uso Não-Comercial-Compartilhamento pela mesma Licença 2.5 Brasil. Para ver uma cópia desta licença, visite http://creativecommons.org/licenses/by-nc-sa/2.5/br/ ou envie uma carta para Creative Commons, 171 Second Street, Suite 300, San Francisco, California 94105, USA.