Drogas off label na COVID-19: Mecanismo de ação e atualizações The use of off label drugs for COVID-19: Mechanisms of action and updates

Bárbara Passos Paes Barreto, Gabriela Gursen de Miranda Arraes, Larissa da Silva Cambraia, Letícia Fonseca Macedo, Maria Eduarda Silveira Bührnheim, Rita de Cássia Silva de Oliveira, Thaisy Luane Gomes Pereira Braga, Thalita da Rocha Bastos

Abstract


Introdução: Com o surgimento de demandas urgentes da pandemia da COVID-19 e a ausência de terapias comprovadamente eficazes, a busca por medicamentos que possuam efeitos positivos no tratamento para a doença se tornou um grande desafio para médicos e pesquisadores. Nesse sentido, dados sobre o mecanismo de ação das medicações mais estudadas ainda são escassos. Metodologia: Com o objetivo de compilar os possíveis mecanismos de ação de medicações off label na COVID-19, foi realizada uma revisão nas bases de dados: Periódicos CAPES, Scielo, MEDLINE/PubMed, LILACS e enciclopédias validadas, sendo considerados artigos de dezembro de 2019 a abril de 2021. Resultados/Discussão: Foram revisados 77 artigos, os quais apresentaram como uso off label na COVID-19. Alguns antiparasitários, como a ivermectina e a nitazoxanida, têm demonstrado eficácia contra a atividade viral em pesquisas in vitro nas últimas décadas, entretanto, estudos também apontam a necessidade de doses acima das permitidas para ação eficaz in vivo. Em relação aos anti-inflamatórios não esteroidais, o seu uso está relacionado aos efeitos analgésicos e antipiréticos, uma vez que a inflamação local envolve a produção de prostaglandinas pela COX-2 inflamatória e o recrutamento e a ativação de células efetoras. O uso de corticoides foi associado à redução dos níveis de citocinas pró-inflamatórias e, devido a sua capacidade de diminuir a proliferação celular, estão sendo utilizados como adjuvantes no tratamento de formas graves da COVID-19. Já no que diz respeito aos anticoagulantes, a heparina foi a mais amplamente utilizada, sendo o seu mecanismo de ação sugerido o aumento dos níveis de antitrombina III com consequente redução de efeitos trombóticos, relatados na COVID-19. Diversas classes de antibióticos têm sido empregadas no manejo da COVID-19 por apresentarem afinidade por tecidos pulmonares, propriedades antivirais e imunomodulatórias, bem como eficácia contra infecções bacterianas associadas à doença. Quanto aos antivirais, alguns foram testados para o manejo da COVID-19. Dentre eles, o Remdesivir obteve mais sucesso, devido ao seu mecanismo de ação como terminador de cadeia, que coíbe a replicação viral. Esse fármaco já recebeu autorização da Food and Drug Administration para uso em pacientes internados com o quadro confirmado da doença ou com suspeita. No entanto, mais estudos ainda precisam ser feitos para confirmar a eficácia dessa droga. Conclusão: Diversos fármacos foram empregados de maneira off label no manejo de pacientes com suspeita ou comprovação de infecção pelo SARS-CoV-2 a partir de experiências prévias em pandemias ou epidemias de vírus semelhantes ao da COVID-19, alguns já foram descartados, pela relação desproporcional risco versus benefício e outros têm se mostrado potenciais agentes terapêuticos. Apesar disso, poucos mecanismos de ação e efetividade absoluta foram estabelecidos na literatura. Assim, mais estudos são necessários para elucidar tais questionamentos, a fim de apontar uma droga segura e eficaz de fato na COVID-19.

 


Keywords


Infecções por Coronavirus, Farmacologia, Preparações farmacológicas.

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DOI: https://doi.org/10.34119/bjhrv4n3-053

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