Pathological effects of drugs on the gastrointestinal tract: a review
ABSTRACT Drug-induced injury of the gastrointestinal (GI) tract is increasingly common but generally under-recognized. Although there is an overwhelming number of drugs that are associated with adverse GI effects, there is a limited number of characteristic injury patterns that should prompt consideration of drug-induced GI pathology. These include the following: erosions, ulcers, and strictures; crystal deposition; parietal cell changes; reactive gastropathy; pseudodysplastic changes; microscopic colitis; infectious or necrotizing enterocolitis; ischemic colitis; focal active colitis; and increased epithelial apoptosis. This article reviews morphological and pathophysiological features of some of the more common and pathologically recognizable drug-related injury patterns and provides a practical guide for the recognition and diagnosis of drug-induced pathology in the upper and lower GI tract.
Osteoporosis International 10/2014; 26(1). DOI:10.1007/s00198-014-2942-8 · 4.17 Impact Factor
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ABSTRACT: A toxicity / toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. . This study extends the observations in newborn baboons (McGill et al., Gastroenterology 73, 512-517, 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff ), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1β, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA (2014) and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.Food and Chemical Toxicology 01/2015; 77. DOI:10.1016/j.fct.2014.12.022 · 2.61 Impact Factor
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ABSTRACT: Many drugs and chemical agents can cause enteritis and colitis, producing clinical gastrointestinal side effects, the most common of which are diarrhoea, constipation, nausea and vomiting. Significant histological overlap exists between some patterns of medication or chemical injury and various disease entities. A particular medication may cause multiple patterns of injury and may mimic common entities such as coeliac disease, Crohn's disease, infectious enteritis and colitis. Thus, given the common absence of specific histopathological features, the diagnosis often relies upon thorough clinicopathological correlation. This review concentrates on selected examples of medication-induced injury of the intestinal tract in which the pathology can be recognized, particularly on biopsies, with a focus on newly described medication-induced gastrointestinal effects.Histopathology 01/2015; 66(1). DOI:10.1111/his.12598 · 3.30 Impact Factor