Physiological and drug bases of anxiety disorder
DOI:
https://doi.org/10.33448/rsd-v9i9.7780Keywords:
Anxiety; Neurophysiology; Anxiolytics.Abstract
Anxiety disorder is one of the most prevalent neuropsychiatric conditions with about 264 million people worldwide living with this disorder. It is triggered when an individual faced with a given situation or event is unable to respond to the demands and feels a threat to their existence or essential values. This disorder has a multifactorial nature in its etiology, emphasizing mainly genetic, environmental and neurobiological factors. The main medication agents most used are benzodiazepines and non-benzodiazepines, however the use and recommendation of these agents is limited. This study is classified in a qualitative narrative review. In addition, the drug treatment of symptoms completely remains unknown. Thus, this review aims to discuss the main physiological bases of this disorder, as well as the treatment and its effects.
References
Abadinsky, H. (2008). Drug use and abuse: a comprehensive introduction. 6ª ed. Belmont: Thomson Wadsworth.
Afonso, A., Reinas, C., Roberto, E., Campos, E., Henrique, E., Andrade, H., Viegas, R., Santos, S., Resende, V. C., Pimentel-Souza, F. (1997). Ansiedade (Serotonina e GABA). A loucura e o controle das emoções. Rev. Psicofisiologia. 1(1 e 2) cap. 5.
Aguirre-Hernández, E., González-Trujano, M. E., Terrazas, T., Santoyo, J. H., Guevara-Fefer, P. (2016). Anxiolytic and sedative-like effects of flavonoids from Tiliaamericana var. mexicana: GABAergic and serotonergic participation. Salud mental. 39(1), 37 – 46.
Almeida-Filho, N., de Jesus Mari, J., Coutinho, E., & Franca, J. F. (1997). Brazilian multicentric study of psychiatric morbidity: methodological features and prevalence estimates. The British Journal of Psychiatry, 171, 524.
Altamura, A. C., Moliterno, D., Paletta, S., Maffini, M., Mauri, M. C., Bareggi, S. (2013). Understanding the pharmacokinetics of anxiolytic drugs. Expert Opinion on Drug Metabolism & Toxicology. 9, 423–440.
Andrade, L. H. S. G. D., & Gorenstein, C. (1998). Aspectos gerais das escalas de avaliação de ansiedade. Rev. psiquiatr. clín. (São Paulo), 285-90.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub.
Amorim, D., Amado, J., Brito, I., Costeira, C., Amorim, N., & Machado, J. (2018). Integrative medicine in anxiety disorders. Complementary therapies in clinical practice, 31, 215-219.
Arango, V., Underwood, M. D., Boldrini, M., Tamir, H., Kassir, S. A., Hsiung, S., Chen, J. J., Mann, J. J. (2001). Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacol. 25(6) 892-903.
Assumpção Jr, F. B., & Kuczynski, E. (2003). Transtorno do Humor. Assumpção Jr FB, Kuczynski E. Tratado de Psiquiatria da Infância e Adolescência. São Paulo: Atheneu, 307-20.
Bari, B. A., Chokshi, V., Schmidt, K. (2020). Locus coeruleus-norepinephrine: basic functions and insights into Parkinson’s disease. Neural Regeneration Research. 15(6), 1006-1013.
Blundel, J. E. (1992). Serotonin and the biology of feending. The American Journal of Clinical Nutrition. 55(1), 155-159.
Bourin, M., Petit-Demouliére, B., Dhonnchadha, B. N., Hascöet, M. (2007). Animal models of anxiety in mice. Fundamental & Clinical Pharmacology. 21(6), .567-574.
Braat, S., & Kooy, R. F. (2015). Insights into GABAAergic system deficits in fragile X syndrome lead to clinical trials. Neuropharmacology, 88, 48-54.
Bremner, J. D., Krystal, J. H., Southwick, S. M., & Charney, D. S. (1996). Noradrenergic mechanisms in stress and anxiety: I. Preclinical studies. Synapse, 23(1), 28-38.
Bruton, L. L., Chabner, B. A., Knollmann, B. C. (2012). Goodman & Gilman: as bases farmacológicas da terapêutica. 12. ed. Rio de Janeiro: McGraw-Hill.
Bystritsky, A. (2006). Treatment-resistant anxiety disorders. Molecular psychiatry, 11(9), 805-814.
Calhoon, G. G., & Tye, K. M. (2015). Resolving the neural circuits of anxiety. Nature neuroscience, 18(10), 1394-1404.
Celada, P., Bortolozzi, A. (2013). Receptores Artigas F. Serotonina 5-HT1A como alvos para agentes de tratamento de distúrbios psiquiátricos: justificativa e status atual da pesquisa. Drogas do SNC. 27, 703–716.
Charlson, F. C., Degenhardti, L., Mclaren, J., Hall, W. K., Lynskey, M. T. (2009). A systematic review of research examining benzodiazepinerelated mortality. Pharmacoepidemiology and Drug Safety. 18(2), 93-103.
Chaves, E. D. C. L., Iunes, D. H., Moura, C. D. C., Carvalho, L. C., Silva, A. M., & Carvalho, E. C. D. (2015). Anxiety and spirituality in university students: a cross-sectional study. Revista brasileira de enfermagem, 68(3), 504-509.
Chuang, S. H., & Reddy, D. S. (2018). Genetic and molecular regulation of extrasynaptic GABA-A receptors in the brain: therapeutic insights for epilepsy. Journal of Pharmacology and Experimental Therapeutics, 364(2), 180-197.
Coates, V., Beznos, G. W., & Françoso, L. A. (2003). Medicina do adolescente. 2ª. São Paulo, Sarvier.
De-Miguel, F. F., Trueta, C. (2005) Synaptic and Extrasynaptic Secretion of Serotoin. Cellular and Molecular Neurobiology. 25(2), 297-312.
Dubovsky, S. L., Thomas, M. (1995). Beyond specificity: effects of serotonin and serotonergic treatments on psychobiological dysfunction. Journal of Psychosomatic Research. 39(4), 429–444.
Dunn, A. J., Swiergiel, A. H., Palamourchouk, V. (2004). Brain circuits involved in corticotropin-releasing factornorepinephrine interactions during stress. Annals of the New York Academy Sciences. 1018, 25-34.
Duval, E. R., Javanbakht, A., & Liberzon, I. (2015). Neural circuits in anxiety and stress disorders: a focused review. Therapeutics and clinical risk management, 11, 115.
Dwarkasing, J. T., Witkamp, R. F., Boekschoten, M. V., Terlaak, M. C., Heins, M. S., Van Norren, K. (2016). Increased hypothalamic serotonin turnover in inflammation-induced anorexia. BMC Neuroscience. 17- 26.
ETKIN, A. (2010). Functional neuroanatomy of anxiety: a neural circuit perspective. Curr Top Behav Neurosci, 2, 251-77.
Fadem, B. (2004). Behavioural Science in medicine. London: Linppicott Williams & Williams.
Fajemiroye, J. O., Da Silva, D. M., De Oliveira, D. R., Costa, E. A. (2016). Treatment of anxiety and depression: medicinal plants in retrospect. Fundamental & Clinical Pharmacology. 30(3), 198-215.
Fajemiroye, J. O., Galdino, P. M., Florentino, I. F., Da Rocha, F. F., Ghedini, P. C., Polepally, P. R., ... & Costa, E. A. (2014). Plurality of anxiety and depression alteration mechanism by oleanolic acid. Journal of Psychopharmacology, 28(10), 923-934.
Farb, D. H., & Ratner, M. H. (2014). Targeting the modulation of neural circuitry for the treatment of anxiety disorders. Pharmacological reviews, 66(4), 1002-1032.
Fasipe, O. J. (2019). The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents. IBRO Reports. 6, 95–110.
Fassoulaki, A., Theodoraki, K., & Melemeni, A. (2010). Pharmacology of sedation agents and reversal agents. Digestion, 82(2), 80-83.
Fedotva, J., Kubatka, P., Büsselberg, D., Shleikin, A. G., Caprnda, M., Dragasek, J., Rodrigo, L., Pohanka, M., Gasparova, I., Nosal, V., Opatrilova, R., Qaradakhi, T., Zulli, A., Kruzliak, P. (2017). Therapeutical strategies for anxiety and anxiety-like disorders using plantderived natural compounds and plant extracts. Biomedicine Pharmacotherapy. 95, 437-446.
Feldman. S., Weidenfeld, J. (2004). Involvement of endogenous glutamate in the stimulatory effect of norepinephrine and serotonin on the hypothalamo-pituitary-adrenocortical axis. Neuroendocrinology. 79(1), 43-53.
Gebauer, D. L., Pagnussat, N., Piato, A. L., Schaefer, I. C., Bonan, C. D., Lara, D. R. (2011). Effects of anxiolytics in zebrafish: similarities and differences between benzodiazepines, buspirone and ethanol. Pharmacology Biochemistry Behavior. 99(3), 480-486.
Goodkind, M. S., Gyurak, A., & Etkin, A. (2018). Functional neurocircuitry and neuroimaging studies of anxiety disorders. In Neurobiology of Mentak Illness (pp. 435-450). Oxford University Press, New York.
Graeff, F. G. (1997). Ansiedade. Neurobiologia das Doenças Mentais. 4ª ed. São Paulo: Lemos.
Graeff, F. G., & Guimarães, F. S. (2005). Fundamentos de psicofarmacologia. In Fundamentos de psicofarmacologia. São Paulo: Atheneu.
Graeff, F. G., Guimarães, F. S., Zuardi, A. W. (1999). Medicamentos antipsicóticos. São Paulo: Atheneu.
Hyde, J., Ryan, K. M., & Waters, A. M. (2019). Psychophysiological Markers of fear and anxiety. Current Psychiatry Reports, 21(7), 56.
Hoyer D., Clarke, D. E., Fosard, J. R., Hartig, P. R., Martin, G. R., Mylecharane, E. J., Saxena, P. R., Humphrey, P. P. (1994). Classificação da União Internacional de Farmacologia de receptores para 5-hidroxitriptamina (Serotonina). Pharmacological Reviews. 46(2), 157-203.
Kapezinski, I. F., Quevedo, J., & Izquierdo, I. (2011). Bases biológicas de transtornos psiquiátricos: uma abordagem translacional. Porto Alegre: Editora Artmed.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., ... & Wang, P. S. (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Jama, 289(23), 3095-3105.
Knight, L. K., & Depue, B. E. (2019). New frontiers in anxiety research: The translational potential of the bed nucleus of the stria terminalis. Frontiers in psychiatry, 10, 510.
Koob, G. F., Arends, M. A., Le Moal, M. (2014). Introduction to the Neuropsychopharmacology of Drug Addiction. In: Drugs, Addiction, and the Brain.
Lacy, C. F., Armstrong, L. L., Goldman, M. P., Lance, L. L. (2009). Medicamentos Lexi- Comp: uma fonte abrangente para médicos e profissionais da saúde. 1ª Ed. Barueri, São Paulo: Manole.
Lemonde, S., Turecki, G., Bakish, D., Du, L., Hrdina, P. D., Bown, C. D., Sequerira, A., Kushwaha, N., Morris, S. J., Baseak, A., Ou, X. M., Albert P. R. (2003). Impared repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. Journal of the Neurological Sciences. 23(25), 8788-8799.
Lobo, I. A., & Harris, R. A. (2008). GABAA receptors and alcohol. Pharmacology Biochemistry and Behavior, 90(1), 90-94.
Li, C., Wu, X., Liu, S., Zhao, Y., Zhu, J., Liu, K. (2019). Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases. Frontiers in Neuroscience. 13, 869.
Mackenzie, J. W. (1989). Daycase anaesthesia and anxiety A study of anxiety profiles amongst patients attending a Day Bed Unit. Anaesthesia, 44(5), 437-440.
Maier, W., & Falkai, P. (1999). The epidemiology of comorbidity between depression, anxiety disorders and somatic diseases. International clinical psychopharmacology, 14, S1-6.
Martin, E. I., Ressler, K. J., Binder, E., & Nemeroff, C. B. (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatric Clinics, 32(3), 549-575.
Margis, R., Picon, P., Cosner, A. F., Silveira, R. de. O. (2003). Relação entre estressores, estresse e ansiedade. Revista de Psiquiatria. 25(1), 65-74.
Masiulis, S., Desai, R., Uchański, T., Martin, I. S., Laverty, D., Karia, D., ... & Steyaert, J. (2019). GABA A receptor signalling mechanisms revealed by structural pharmacology. Nature, 565(7740), 454-459.
Mathew, J. S., Rebecca, B. P., Dennis, S. C. (2008). Recent Advances in the Neurobiology of Anxiety Disorders: Implications for Novel Therapeutics. American Journal of Medical Genetics. 148(2), 89–98.
Mccorvy, J. D., Roth, B.L. (2015) Structure and function of serotonin G protein-coupled receptors. Pharmacology & Therapeutics. 150, 129-42.
Miguel, E. C., Gentil, V., & Gattaz, W. F. (2011). Clínica psiquiátrica. Departamento e Instituto de Psiquiatria da Faculdade de Medicina da USP. São Paulo.
Mouton, P. R., Pakkenberg, B., Gundersen, H. J., Price, D. L. (1994). Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals. Journal of Chemical Neuroanatomy. 7, 185-190.
Murrough, J. W., Yaqui, S., Sayed, S., Charney, D. S. (2015). Emerging drugs for the treatment of anxiety. Expert Opinion on Emerging Drugs. 20(3), 393-406.
Nojoumi. M., Ghaeli, P., Salimi, S., Sharifi, A., Raisi, F. (2016). Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study. Iranian Journal of Psychiatry. 11(3), 191–197.
Ochoa-de la Paz, L. D., González-Andrade, M., Pasantes-Morales, H., Franco, R., Zamora-Alvarado, R., Zenteno, E., ... & Gulias-Cañizo, R. (2018). Differential modulation of human GABA C-ρ1 receptor by sulfur-containing compounds structurally related to taurine. BMC neuroscience, 19(1), 47.
Petroff, O. A. (2002). Book review: GABA and glutamate in the human brain. The Neuroscientist, 8(6), 562-573.
Rang, H. P., Dale, M. M., Ritter, J., Flower, R. J., Henderson, G. (2011). Farmacologia. 7° ed. Rio de Janeiro: Editora Elsevier.
Ressler, K. J., & Nemeroff, C. B. (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and anxiety, 12(S1), 2-19.
Ribeiro, H. K. P., Santos, J. D. M., Silva, M. D. G., Medeiro, F. D. D. A., & Fernandes, M. A. (2019). Anxiety disorders as a cause of work absenteeism. Revista Brasileira de Saúde Ocupacional, 44.
Ribeiro, L., Kapczinsk, F. (2000). Ansiedade: Bases Biológicas dos Transtornos Psiquiátricos. Porto Alegre: Artmed.
Sadock, B. J., Sadock, V. A., & Ruiz, P. (2010). Compêndio de Psiquiatria-: Ciência do Comportamento e Psiquiatria Clínica. Artmed Editora.
Sampaio, T. I. Dos. S., Melo, N. C., Paiva, B. T. DE. F., Aleluia, G. A. DA. S., Da Silava Neto, F. L. P., Silva, H. R. Da., Keita. H., Cruz, R. A. S., Sánchez-Ortiz, B. L., Pineda-Peña, E. A., Balderas, J. L., Navarrete, A., Carvalho, J. C. T. (2018). Leaves of Spondiasmombin L. a traditional anxiolytic and antidepressant: Pharmacological evaluation on zebrafish (Danio rerio). Journal of Ethnopharmacology. 5(224), 563-578.
Schatzberg, A. F., Nemeroff, C. B. (2004). Livro de texto de psicofarmacologia. 3º ed. Washington: The American PsychiatricPublishing.
Sigel, E., & Steinmann, M. E. (2012). Structure, function, and modulation of GABAA receptors. Journal of Biological Chemistry, 287(48), 40224-40231.
Silva Filho, O. C. D., & Silva, M. P. D. (2013). Transtornos de ansiedade em adolescentes: considerações para a pediatria e hebiatria.
Stein, D. J. (2001). Comorbidity in generalized anxiety disorder: impact and implications. The Journal of Clinical Psychiatry, 62, 29-34.
Stein, D. J., & Seedat, S. (2004). Unresolved questions about treatment-resistant anxiety disorders. CNS spectrums, 9(10), 715-715.
Sivilotti, M. L. A. (2016) Flumazenil, naloxona e o 'coquetel de coma. British Journal of Clinical Pharmacology. 81, 428–36.
Tubbs, R.S., Loukas, M., Shoja, M. M., Mortazavi, M. M., Cohen-Gadol, A. A. (2011). Felix Vicq d’Azyr (1746-1794): early founder of neuroanatomy and royal French physician. Child’s Nervous System. 27, 1031-1034.
Watanabe, M., Maemura, K., Kanbara, K., Tamayama, T., & Hayasaki, H. (2002). GABA and GABA receptors in the central nervous system and other organs. In International review of cytology (Vol. 213, pp. 1-47). Academic Press.
Wells, B. G., DiPiro, J. T., Schwinghammer, T. L., & DiPiro, C. V. (2016). Manual de farmacoterapia. McGraw Hill Brasil.
World Health Organization. (2017). Depression and other common mental disorders: global health estimates (No. WHO/MSD/MER/2017.2). World Health Organization.
Zhu, S., Noviello, C. M., Teng, J., Walsh, R. M., Kim, J. J., & Hibbs, R. E. (2018). Structure of a human synaptic GABA A receptor. Nature, 559(7712), 67-72.
Zifa, E., Fillion, G. (1992). 5-Hydroxytryptamine receptors. Pharmacology Reviews. 44(3), 401-458.
Zmudzka, E., Salaciak, K., Sapa, J., Pytka, K. (2018). Serotonin receptors in depression and anxiety: Insights from animal studies. Life Sciences. 2010, 106-124.
ZUARDI, A. W. (2017). Características básicas do transtorno de ansiedade generalizada. Suplemento Temático: Psiquiatria. Cap. 5. Medicina (Ribeirão Preto, Online.), 50, 51-55.
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Copyright (c) 2020 Carla Laíne Silva Lima; Sandra Machado Lira; Marcelo Oliveira Holanda; José Ytalo Gomes da Silva; Vinícius Bandeira Moura; Jennifer de Sousa Melo Oliveira; Beatriz Farias Serra; Amanda Gomes Queiroz Freitas; Nicolas Maurício Girão; Maria Izabel Florindo Guedes
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