Abstract
Purpose: Diarrhea and dehydration caused by enteric infections is a major factor of morbidity and mortality worldwide. Secretory diarrhea can be devastating especially among infants, children, and HIV infected people and can result in death of more than 50% of its victims for without adequate rehydration, patients are at maximum risk during the first 6-18 hours. Hence, it is a leading cause of morbidity and mortality worldwide. Diarrhea is experienced by over 50% of AIDS patients at some time or other during the course of their illness, which is an important cause of increased morbidity and mortality in them. Currently, the standard-of-care therapy focuses only on rehydration therapy to combat dehydration and antibiotic therapy that targets the infectious agent only. Though, antimicrobial drugs have been the key treatment for diarrhea but, with the emergence of resistant strains the search for novel targets/drugs is on, for diarrhea still continues to kill millions.
Methods: A literature search was done using secretory diarrhea and Crofelemer, as key words using PubMed (Medline), ProQuest, Cochrane Library, Medscape and Google Scholar search engines from January 2012 to December 2014. The types of articles included in this review were original research, review papers, recent patents and editorials from various medical schools across the globe. Though, it was practically not possible to include all studies, one can marvel at all the proclaimed mechanism of action of Crofelemer in this study.
Results: Crofelemer, a channel blocker of intestinal chloride channels such as the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and the Calcium Activated Chloride Channels (CaCCs) plays significant roles in providing symptomatic relief in secretory diarrhea.
Conclusion: Crofelemer is a first-in-class agent that possesses a unique mechanism of action through dual inhibition of both the intestinal chloride channels in secretory diarrhea.
Keywords: CaCCs, CFTR, chloride channels, crofelemer, HIV, secretory diarrhea.
Graphical Abstract