Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0740441 (acute diarrhea)
 2,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of advanced non-small cell lung cancer (NSCLC) has progressed over the last 3 decades due to advances in chemotherapeutic drugs and targeted agents improving survival and quality of life. In particular erlotinib, an orally available human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor advancing through clinical trials for the treatment of various human malignancies in a large placebo-controlled phase III study, has shown a significantly better OS vs. placebo suggesting its potential benefits in third line and possibly in second line treatments. The association of erlotinib with ionizing radiation has been recently published showing an enhancing antitumor activity and good tolerance. No information are available on side effects when erlotinib is associated with abdominal hypofractionated radiotherapy although diarrhoea is the most known side effect dose-limiting toxicity when the abdomen is treated. Here we report a fatal acute diarrhoea in a metastatic NSCLC patient taking erlotinib during abdominal hypofractionated radiotherapy for metastatic spinal cord compression (MSCC).
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PMID:Acute and fatal diarrhoea after erlotinib plus abdominal palliative hypofractionated radiotherapy in a metastatic non-small cell lung cancer patient: a case report. 1844 70

Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.
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PMID:A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril. 2266 49

The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.
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PMID:Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole. 3236 2