Cytotoxicity of Thiopurine Drugs in Patients with Inflammatory Bowel Disease

Abstract

The effectiveness of thiopurine drugs in inflammatory bowel disease (IBD) was confirmed more than a half-century ago. It was proven that these can be essential immunomodulatory medications. Since then, they have been used routinely to maintain remission of Crohn’s disease (CD) and ulcerative colitis (UC). The cytotoxic properties of thiopurines and the numerous adverse effects of the treatment are controversial. However, the research subject of their pharmacology, therapy monitoring, and the search for predictive markers are still very relevant. In this article, we provide an overview of the current knowledge and findings in the field of thiopurines in IBD, focusing on the aspect of their cytotoxicity. Due to thiopurines’ benefits in IBD therapy, it is expected that they will still constitute an essential part of the CD and UC treatment algorithm. More studies are still required on the modulation of the action of thiopurines in combination therapy and their interaction with the gut microbiota.

A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics

“…Most patients with thiopurine-induced hepatotoxicity have a high concentration of 6-methylmercaptopurine ribonucleotide or 6-MMPR (formed by TPMT) one week after treatment initiation. There is also evidence that elevated levels of 6-methylmercaptopurine or 6-MMP (formed by TPMT) are correlated with hepatotoxicity 2 . To address these side effects, improved drug delivery mechanisms such as nano-formulations and delayed-release tablets are in development, none of which are currently in clinical practice 3 .…”

aiCRISPRL: An Artificial Intelligence Platform for Stem Cell and Organoid Simulation with Extensive Gene Editing Capabilities

“…While the MMR process recognizes these mutations, it is unable to repair them resulting in replication arrest and apoptosis. Additional cytotoxicity from 6-TGNs is the result of inhibiting the RAC1 protein that regulates the diverse downstream signals of the RAC1-VAV pathway in various cancer cells [26].…”

“…Additional cytotoxicity from 6-TGNs is the result of inhibiting the RAC1 protein that regulates the diverse downstream signals of the RAC1-VAV pathway in various cancer cells [26].…”

Perioperative Assessment and Optimization in Major Colorectal Surgery: Medication Management

“…Adverse effects include leukopenia, gastrointestinal intolerance, hepatotoxicity, pancreatic toxicity, and increased risk of nonmelanoma skin cancer and lymphoma. 9 Several studies including a Cochrane review have not identified any increase in perioperative infectious complications or morbidity with use of purine analogues. 4 6 The current recommendation is to withhold purine analogues the day of surgery and resume when oral medications are given, if renal function remains within normal limits.…”

“…Adverse effects include leukopenia, gastrointestinal intolerance, hepatotoxicity, pancreatic toxicity, and increased risk of nonmelanoma skin cancer and lymphoma. 9 Several studies including a Cochrane review have not identified any increase in perioperative infectious complications or morbidity with use of…”