ABSTRACT
BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.
Subject(s)
Adenosine Monophosphate/adverse effects , Alanine/adverse effects , COVID-19 Drug Treatment , Hydroxychloroquine , Lopinavir/adverse effects , Ritonavir/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Drug Combinations , Humans , Hydroxychloroquine/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2ABSTRACT
Se sintetizaron varios nuevos derivados del 1,2,3,4, tetrahidrocarbazol, 5,6-dihidrobenzo (alfa) carbazol, 3-metilindol y benzimidazol, que se ensayaron sobre cultivos del Trypanosoma cruzi, en el medio líquido de Warren. El 6-cloro-y el 6,8 dicloro-N-(1-etil-N-dimetilamino) 1,2,3,4, tetrahidrocarbazol fumarato resultaron los más potentes inhibidores del crecimiento del parásito. Estos carbazoles fueron relativamente más activos que los preparados previamente por Poliakoff y col
Subject(s)
Carbazoles/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanosoma cruzi/drug effectsABSTRACT
Se sintetizaron varios nuevos derivados del 1,2,3,4, tetrahidrocarbazol, 5,6-dihidrobenzo (alfa) carbazol, 3-metilindol y benzimidazol, que se ensayaron sobre cultivos del Trypanosoma cruzi, en el medio líquido de Warren. El 6-cloro-y el 6,8 dicloro-N-(1-etil-N-dimetilamino) 1,2,3,4, tetrahidrocarbazol fumarato resultaron los más potentes inhibidores del crecimiento del parásito. Estos carbazoles fueron relativamente más activos que los preparados previamente por Poliakoff y col (AU)
Subject(s)
Trypanocidal Agents/chemical synthesis , Carbazoles/pharmacology , Trypanosoma cruzi/drug effectsABSTRACT
Several new 1,2,3,4-tetrahydrocarbazole, 5,6-dihydrobenzo(alpha) carbazole, 3-methylindole and substituted benzimidazolyl compounds were synthesized and assayed for their action on growth of Trypanosoma cruzi, cultured in Warren's liquid medium. 6-chloro and 6,8-dichloro-N-(1-ethyl-N-diethylamino)-1,2,3,4-tetrahydrocarbazole++ fumarate resulted the more active in inhibiting growth of the parasite. The new compounds were apparently more effective than those prepared previously by Poliakoff et al. (5).
Subject(s)
Carbazoles/chemical synthesis , Trypanocidal Agents/chemical synthesis , Trypanosoma cruzi/drug effects , Animals , Carbazoles/pharmacology , Structure-Activity Relationship , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/growth & developmentABSTRACT
Several new 1,2,3,4-tetrahydrocarbazole, 5,6-dihydrobenzo(alpha) carbazole, 3-methylindole and substituted benzimidazolyl compounds were synthesized and assayed for their action on growth of Trypanosoma cruzi, cultured in Warrens liquid medium. 6-chloro and 6,8-dichloro-N-(1-ethyl-N-diethylamino)-1,2,3,4-tetrahydrocarbazole++ fumarate resulted the more active in inhibiting growth of the parasite. The new compounds were apparently more effective than those prepared previously by Poliakoff et al. (5).