Pharmacology
Summary
Diarrhea is described as having loose or watery stools three or more times a day, stemming from the intestine's inability to absorb adequate water or from its active secretion of it. While acute diarrhea is often attributed to infections, chronic diarrhea tends to arise from functional disorders or systemic illnesses. Lifestyle modifications are typically preferred, but if necessary, several antidarrheal agents are available. One such agent is bismuth subsalicylate, recognized for its antimicrobial and antisecretory properties, and is used to treat traveler's diarrhea. However, it carries a risk of inducing Reye’s syndrome in pediatric patients. Loperamide, a mu-opioid agonist, functions by prolonging colonic transit time, leading to enhanced water absorption from the intestinal contents. Eluxadoline, an innovative drug that activates mu and kappa opioid receptors while concurrently antagonizing delta opioid receptors. Diphenoxylate, a mu-opioid agonist that has some ability to cross the BBB is often combined with atropine to deter misuse. Finally, vipomas and carcinoid tumors can cause secretory diarrhea, which can be treated with octreotide, a synthetic somatostatin analog that can also be used for diarrhea secondary to chemotherapy, HIV, or short bowel syndrome.
Lesson Outline
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FAQs
Diarrhea, defined by three or more loose or watery bowel movements per day, is a prevalent condition that's usually self-limiting. The underlying mechanisms involve either a decrease in intestinal water absorption or an increase in its active secretion. While infectious agents can lead to acute diarrhea, chronic episodes often originate from functional disorders or systemic illnesses.
Antidiarrheal agents are discouraged in patients exhibiting bloody diarrhea or fever because these symptoms might denote serious underlying conditions, like certain bacterial infections. It's essential to diagnose and address the root cause in these cases rather than just alleviating the symptoms.
Adsorptive agents like kaolin-pectin and bismuth subsalicylate act against diarrhea by binding to the toxins that trigger it and by preventing bacteria from adhering to the intestinal wall. Bismuth subsalicylate stands out due to its dual antimicrobial and antisecretory properties. Notably, while effective against traveler’s diarrhea, it can cause transient side effects like darkening of the stool and tongue. There's also a risk of salicylate toxicity and an increased chance of Reye’s syndrome in children.
Opioid agonists, including diphenoxylate and loperamide, play a crucial role in managing diarrhea. They activate µ-opioid receptors in the gastrointestinal tract, leading to enhanced colonic segmenting activity, prolonged colonic transit time, and improved water absorption. Loperamide, a µ-opioid agonist that doesn't cross the blood-brain barrier, is effective for both acute and chronic types of diarrhea, such as those seen in diarrhea-predominant IBS and inflammatory bowel disease. Diphenoxylate, on the other hand, can cross the blood-brain barrier and is combined with atropine to deter misuse. It's essential to note the potential for abuse with all opioid drugs, especially when taken in non-therapeutic dosages or combined with specific inhibitors.
