Prediction of adverse drug reactions in geriatric patients admitted to intensive care units.

INTRODUCTION: Intensive care units (ICUs) pose challenges in managing critically ill patients with polypharmacy, potentially leading to adverse drug reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. ADR screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR=28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: These data suggest that employing the severity and clinical prognosis scores used in ICUs is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

Synthesis of New Hybrid Derivatives from Metronidazole and Eugenol Analogues as Trypanocidal Agents.

BACKGROUND: The search for new drug compounds is always challenging and there are several different strategies that involve the most varied and creative approaches in medicinal chemistry. One of them is the technique of molecular hybridisation: forming a hybrid compound from two or more pharmacophoric subunits. These hybrids may maintain the characteristics of the original compound and preferably show improvements to its pharmacological action, with reduced side effects and lower toxicity when compared to the original components. This study specifically focuses on synthesising hybrid molecules which demonstrate trypanocidal activity against the epimastigote and trypomastigote forms of Trypanosoma cruzi. METHODS: In this context, this study centres on the synthesis of a novel structural scaffold via molecular hybridisation; by using a triazole species to link a metronidazole unit to a eugenol analogue unit, the objective being to combine their therapeutic properties into a new molecular structure. The resulting hybrid molecules were evaluated against T. cruzi which is responsible for high incidences of trypanosomiasis in tropical countries such as Brazil. RESULTS: The results of this study showed an improvement in the anti-parasitic activity of the hybrid compounds with the best result coming from hybrid compounds [8] and [9], which present an activity similar to the control drug benznidazole. The new compounds, utilising a triazole species as a coupling connector, demonstrated promising results and has highlighted the path for planning similar structural patterns to investigate new compounds. CONCLUSIONS: In summary, we can conclude that the synthesised hybrid compounds demonstrate that using a triazole to link metronidazole with natural phenols, produces hybrid molecules that are promising as a new class of compounds of therapeutic interest for further investigation.