Terapia a longo prazo com lítio e o risco de danos renais: revisão integrativa da literatura / Long-term lithium therapy and the risk of kidney damage: integrative literature review

Este estudo objetivou avaliar os potenciais efeitos adversos nos rins associado ao tratamento de longo prazo com lítio em pacientes com transtorno bipolar, a partir de uma revisão integrativa literatura. Os artigos foram identificados nas bases de dados SciELO, Medline (Pubmed) e Biblioteca Virtual em Saúde (BVS), publicados entre 2010 e 2021. Aplicados os critérios de inclusão e exclusão, identificaram-se 18 artigos para a análise. Verificou-se que o tratamento com lítio durante um período prolongado está associado à redução da taxa de filtração glomerular, porém, outras variáveis devem ser consideradas como idade e comorbidades associadas. Por outro lado, não foi associado evolução da doença renal crônica em estágio terminal por uso do medicamento. A investigação dos estudos revelou que a droga em doses terapêuticas e com monitoramento laboratorial contínuo não demonstrou toxicidade ou efeitos colaterais severos nos rins sendo a sua descontinuação relacionada com exarcebações do humor. [au]

This study aimed to assess the potential adverse effects on the kidneys associated with long-term lithium treatment in patients with bipolar disorder, based on an integrative literature review. The articles were identified in the SciELO, Medline (Pubmed) and Virtual Health Library (VHL) databases, published between 2010 and 2021. After applying the inclusion and exclusion criteria, 18 articles were identified for analysis. It was found that treatment with lithium for a prolonged period is associated with a reduction in the glomerular filtration rate, however, other variables must be considered, such as age and associated comorbidities. On the other hand, evolution of end-stage chronic kidney disease due to drug use was not associated. The investigation of the studies revealed that the drug at therapeutic doses and with continuous laboratory monitoring did not show toxicity or severe side effects in the kidneys and its discontinuation was related to mood exacerbations. [au]

Solid-State Form Characterization of Riparin I.

Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5), obtained by the same synthesis process, were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), DSC-photovisual, Thermogravimetry (TG), Fourier Transform Infrared (FTIR), Pyrolysis (Pyr-GC/MS), X-ray Powder Diffraction (PXRD), and Solid-State Nuclear Magnetic Resonance (ssNMR) techniques. Batches of riparin I with different crystal habits resulting in crystallization impurities were observed, which can be attributed to the presence of triethylamine. The main differences were observed by DSC, PXRD, and ssNMR analysis. DSC curves of RIP-2 and RIP-3 presented endothermic peaks at different temperatures of fusion, which can be attributed to the mixture of different crystalline forms. PXRD and ssNMR results confirmed crystallinity differences. The results offer evidence of the importance of controlling the reproducibility of the synthesis in order to obtain the adequate morphology for therapeutic efficacy and avoiding future problems in quality control of riparin I products.

Correlation of thermal analysis and pyrolysis coupled to GC-MS in the characterization of tacrolimus.

In recent years, thermal analysis has assumed major role in the pharmaceutical industry because it can be used to evaluate the stability both in the control of raw materials and the finished product, having employment potential in the development and characterization of new products and assessment processes. Tacrolimus (TCR) is a macrolide lactone with potent immunosuppressive activity. The purpose of this study was to characterize tacrolimus raw material using Thermal analysis and Pyrolysis coupled to Gas chromatography-Mass spectrometry (Pyr-GC-MS). It was analyzed four samples of tacrolimus named TCR A, B, C and D. Thermal analysis experiments was performed in Shimadzu equipment, under nitrogen and synthetic air atmosphere in different heating rate. Pyrolysis analysis was conducted in isothermal conditions of 300°C and 400°C coupled to GC-MS, in which the mass spectrometer was operated in scan mode to detect ions in the range of mass of m/z 25-900. The thermal studies by DSC, DTA and DSC-Photovisual showed desolvation process for all tacrolimus raw materials and TG-dynamical demonstrated two pseudo-polymorphic forms (monohydrate and sesquihydrate) of tacrolimus. It was observed good correlation between the stoichiometric mass losses of the TG-dynamical and identification of product ion in Pyr-GC/MS technique. It was possible to correlate the five pyrolytic product ions with the Ozawa kinetic analysis from the thermal decomposition of TG-dynamical. The thermal studies (DSC, DSC-Photovisual, DTA and TG-dynamical) were applied in the thermal characterization of the raw materials of tacrolimus which showed pseudo-polymorphic forms, which must be monitored by pharmaceutical industry, avoiding future problems in pharmaceutical process, chemical stability and bioavailability of the tacrolimus product.