Successful treatment of severe diarrhea has traditionally relied upon opiates or opiate derivatives. Recent advances in our understanding of intestinal fluid and electrolyte absorption have provided the opportunity to develop therapeutic agents specific for various points in the secretory and absorptive process. Present and proposed antidiarrheal agents, in addition to antimotility activity, will be capable of stimulating intestinal fluid absorption, inhibiting intestinal fluid secretion, or both. The mechanism(s) of action and clinical implications for proposed antidiarrheal agents are reviewed.
PIP: Recent advances in understanding of intestinal fluid and electrolyte absorption have paved the way for the development of antidiarrheal agents specific for various points in the secretory and absorptive process. Examples of potential antidiarrheal agents include clonidine and lidamidine in diabetic diarrhea, somatostatin in hormonally mediated diarrhea, and prostaglandin synthetase inhibitors in inflammatory diarrhea. Physiological principles of electrolyte transport that underlie these new developments include the capability in both the small and large intestine of the epithelium in absorbing and secreting water and electrolytes; the responsibility of the villus epithelium for sodium chloride/water absorption and of the crypt epithelium for chloride/water secretion; the existence of a continuum between absorption and secretion determined by the sum of the absorptive and secretory drives on the enterocyte; the role of neuroendocrine transmitters, hormones, and inflammatory elements released systemically or locally as stimuli regulating these processes; the fact that most of these stimuli activate specific receptors on enterocytes; and the altering effect of these stimulus-receptor interactions on intercellular levels of cyclic nucleotides or calcium, in turn producing net secretion by diminishing absorption and/or stimulating secretion. Also under investigation as antidiarrheal agents are calcium and calmodulin antagonists, enkephalins, lithium, berberine, oral organic acids, and chloride channel blockers.