Derivatives of 3H-spiro1-benzofuran-2, 1’-cyclohexanes: immunostimulants for veterinary use / Derivados de 3H-espiro1-benzofurano-2, 1’-ciclohexanos: inmunoestimulantes de uso veterinario

Four 3H-spiro1-benzofuran-2, 1’-cyclohexanes were synthesized from filifolinol, two of which are reported for the first time. Docking molecular studies were carried out to determine in silico whether these derivatives have similar immunostimulant activity to that reported for filifolinol, and its oxidation product, filifolinone. Through of the study of interactions of these compounds with the heterodimer of the protein present in teleost TLR1-TLR2, filifolinol, 3’-filifolinchloride and filifolinyl acetate shows similar interactions between them, allowing to predict that they would have similar immunostimulant activity, but different to filifolinone and filifolinane or that they would act by a different mechanisms.

Cuatro 3H-spiro1-benzofuran-2, 1'-ciclohexanos se sintetizaron a partir de filifolinol, dos de los cuales son reportados por primera vez. Se llevaron a cabo estudios de docking molecular para determinar in silico si estos derivados tienen actividad inmunoestimulante similar a la reportada para filifolinol y su producto de oxidación, filifolinona. A través del estudio de las interacciones de estos compuestos con el heterodímero de la proteína presente en teleósteos TLR1-TLR2 se estableció que el filifolinol, 3'-cloruro de filifolinilo y acetato de filifolinilo tienen interacciones similares con el heterodímero, lo que permite predecir que entre ellos tendrían una actividad simi- lar, pero diferente a la de la filifolinona y filifolinano o que estos últimos actuarían por diferentes mecanismos.

Interacciones de medicamentos y eventos adversos en fármacos utilizados en una unidad de cuidados intensivos / Drug interactions and adverse events induced by drugs used in an intensive care unit

Background: Eleven percent of hospitalized patients experience drug-drug interactions (DDIs), elevating morbidity, mortality and health care costs. Polypharmacy is very common in intensive care units (ICUs), increasing the risks of drug adverse events (AEs). Aim: To assess DDIs in ICU patients. Material and Methods: A prospective study conducted in the ICU of a private hospital, evaluating the frequency of DDIs, AEs developed and their relationship. Patients admitted to the ICU were included if they stayed at least three days in the ICU and received at least one studied drug Results: Thirty fve patients aged 59 ± 16 years (24 women) were enrolled in the study. Seventy six DDIs and 60 AEs were recorded. Statistically signifcant associations were only found for midazolam-fentanyl-propofol with bradycardia and hypotension and amphotericin B-vancomycin and vancomycin-amikacin with acute renal failure (ARF). Relative risks were 10.4 (95 percent confdence intervals (CI) 1.59 - 68) for bradicardia, 5 (95 percent CI 1.082 - 23.4) for hypotension and 6.4 (95 percent CI 1.9 - 21.6) for ARF. The odds ratios were 125.2 (95 percent CI 3 - 250), 12.6 (95 percent CI 1.3 - 77) and 10.8 (95 percent CI 1.3 - 282) respectively. Conclusions: DDIs associated with risk of AEs were fentanyl, propofol and midazolam for bradycardia and hypotension and amphotericin B-vancomycin and vancomycin-amikacin for ARF.