warfarin and Chagas-Disease

3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.

Topics: Amides; Animals; Cell Line; Chagas Disease; Dose-Response Relationship, Drug; Methanol; Mice; Mice, Inbred BALB C; Molecular Structure; Parasitic Sensitivity Tests; Rats; Structure-Activity Relationship; Triazoles; Trypanocidal Agents; Trypanosoma brucei rhodesiense; Trypanosoma cruzi

The aim of this study was to assess the agreement of four renowned interaction lists on potentially severe warfarin drug interactions (DI) in outpatients at a university hospital in Brazil, specifically in subgroups of Trypanosoma cruzi-infected and non-infected patients and those with previous bleeding episodes.. This was a cross-sectional study in which adult outpatients with heart disease and indications for chronic warfarin use were enrolled. The occurrence of potentially severe warfarin DI was evaluated based on the lists provided by three compendia, i.e., Drug Interaction Facts (DIF), Drug Interactions: Analysis and Management (DIAM) and DRUG-REAX, and by the World Health Organization (WHO) Model Formulary. A kappa coefficient was used to calculate the agreement among the sources.. A total of 280 patients were studied. Most patients were female (54.6 %) with an average age of 56.8 (standard deviation 13.1) years. The agreement among the four sources was fair (Fleiss' kappa coefficient = 0.295). T. cruzi-infected individuals were less likely to have severe warfarin DI than non-infected patients (p < 0.05 for DIAM, DRUG-REAX and the WHO Model Formulary). Potentially severe DI were more frequent in patients with previous bleeding episodes, based on the DIF compendia (p = 0.007).. This evaluation of warfarin DI revealed that the disagreement between compendia is also observed in clinical practice. T. cruzi infection is associated with a lower prevalence of potentially severe warfarin DI, but with a wider variation in its detection. Our results suggest a wide spectrum of discrepancies in detecting heart disease patients at higher risk for severe warfarin DI and a possible heterogeneity in clinical guidance.

Topics: Adverse Drug Reaction Reporting Systems; Anticoagulants; Brazil; Chagas Disease; Cross-Sectional Studies; Drug Interactions; Female; Heart Diseases; Hemorrhage; Hospitals, University; Humans; Male; Middle Aged; Outpatients; Polypharmacy; Prevalence; Trypanosoma cruzi; Warfarin

Chagas disease (CD) is frequently associated with cardioembolic stroke in South America. Our objective was to identify the predictors of stroke in a region where CD is endemic.. We screened 305 consecutive cardiopathy patients. Significant predictors of stroke in univariable analyses were included in a multivariable model.. Stroke was more frequent in CD (15.0%) compared with other cardiopathies (6.3%; P=0.015). Other predictors of stroke in univariable analyses were previous diabetes or cardioversion and use of amiodarone, antiplatelet agents, and warfarin. In multivariable analysis, remaining predictors of stroke were CD (odds ratio [OR], 1.09; 95% CI, 1.02 to 1.17), cardioversion (OR, 1.07; 95% CI, 1.02 to 1.13), and diabetes (OR, 1.12; 95% CI, 1.01 to 1.24).. In conclusion, CD is a risk factor for stroke, independent of systolic dysfunction or presence of cardiac arrhythmias.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Chagas Disease; Cohort Studies; Female; Heart Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Platelet Aggregation Inhibitors; Regression Analysis; Risk Factors; Stroke; Warfarin