Pharmacological Efficacy/Toxicity of Drugs: A Comprehensive Update About the Dynamic Interplay of Microbes

Abstract

Oral ingestion is a common, easy to access, route for therapeutic drugs to be delivered. The conception of the gastrointestinal tract as a passive physiological compartment has evolved toward a dynamic perspective of the same. Thus, microbiota plays an important role in contributing with additional metabolic capacities to its host as well as to its phenotypic heterogeneity. These adaptations in turn influence the efficacy and toxicity of a broad range of drugs. Notwithstanding, xenobiotics and therapeutic drugs affecting the microbiome's activity also significantly impact metabolism affecting different organs and tissues, and thereby drugs' toxicity/efficacy effects. Other physiological interfaces (i.e., gut, lungs, and skin) also represent complex media with features about microbiota's composition. In addition, there have been described key regulatory effects of microbes on immunotherapy, because of its potential harnessing the host immune system, mental disorders by modulating neuroendocrine systems and cancer. These alterations are responsible of physiological variations in the response(s) between individuals and populations. However, the study of population-based differences in intestinal microbial-related drug metabolism has been largely inferential. This review outlines major reciprocal implications between drugs and microbes regulatory capacities in pharmacotherapy.

Unravelling the antimicrobial action of antidepressants on gut commensal microbes

“…Also, the same authors found a reduction in abundance at the genus level of Ruminococcus, Adlercreutzia, and an unclassified Alphaproteobacteria in mice treated with desipramine. Likewise, administration of desipramine was also shown to cause important side effects and results in a higher incidence of infections generating gingivitis and dysbiosis of oral microbiota 19 . Other representatives of the tricyclic antidepressants group were previously shown to possess an in vitro antimicrobial effect toward human pathogenic species, such as amitriptyline against Staphylococcus spp., Bacillus spp., and Vibrio cholerae 22 ; www.nature.com/scientificreports/ and imipramine, which inhibited the growth of E. coli and Yersinia enterocolitica 23 .…”

“…Besides, other evidence gathered from animal studies suggested that the antidepressants modulate the composition of the intestinal microbiota 9,[16][17][18] . Administration of TCA desipramine causes important side effects and results in a higher incidence of infections generating gingivitis and dysbiosis of oral microbiota 19 . A prior study revealed that ketamine also modulates the fecal microbiome in the susceptible mice after chronic social defeat stress, suggesting an antidepressant mechanism partly mediated by the modulation of gut microbiota 20 .…”

Drug-Related Enteropathy

“…Dysbiosis is a term used to describe any quantitative and/or qualitative imbalance, dysfunction or disturbance of the gut microbiota and microbiome as an indicator of disease or poor health status [23], and may be caused by a number of risk factors, including medications. Drugs and microbiota have a two-way relationship: drugs exert a significant impact on organs and tissues through their effect on gut microbiota, but in the other hand, microbiota metabolic capacity may affect stability, metabolite production, availability, absorption and thus, increase or decrease efficacy and/or toxicity of different medications [24][25][26]. A number of drugs have been described to alter the composition Drug-Related Enteropathy DOI: http://dx.doi.org/10.5772/intechopen.103734 of the gut microbiota, including antibiotics, proton-pump inhibitors (PPI), nonsteroidal anti-inflammatory drugs (NSAID), opioids, metformin, statins, psychotropics, particularly atypical anti-psychotics, levothyroxine, anticoagulants, antiarrhythmics, and several oncologic medications including chemotherapeutic agents, and targeted therapy [18,[27][28][29][30][31][32][33].…”

Study of Biological Activity and Toxicity of Thiosemicarbazides Carbohydrate Derivatives by <i>in Silico</i>, <i>in Vitro</i> and <i>in Vivo</i> Methods

“…There are a number of classifications of chemical substances for the assessment of acute toxicity [10] [11] [12]. To assess the toxicity of antiparasitic drugs, the classification according to [12] [13] is more suitable.…”