Summary of Antidiarrheals
Transcript for Antidiarrheals
Antidiarrheal medications are used to treat diarrhea, a word which actually means “flow through.”
Diarrhea can be defined as stool that contains fluid weight over 200g of fluid per day. Increased frequency of bowel movement is also common, but not always present.
Now, the small and large intestine are where most of the absorption happens in the GI tract. Both regions contain smooth muscles which perform what’s called peristalsis, which is a series of coordinated wave-like muscle contractions that help squeeze the chyme or the food bolus after it leaves the stomach, in one direction.
Lining the luminal surface of the intestine is a layer called the mucosa, which secretes and absorbs different molecules to change the contents of the intestinal lumen.
The mucosa of the small intestine has a lot of tiny ridges and grooves, each of which projects little finger-like fibers called villi. And in turn, each villus is covered in teeny tiny little microvilli. All of this gives the small intestine plenty of surface area to absorb nutrients and ions.
The large intestine mainly absorbs excess water from the chyme, and that helps condense it into dry fecal matter, which eventually ends up in the rectum.
There are four main causes for diarrhea: osmotic, secretory, inflammatory, and diarrhea associated with deranged, or unstable, intestinal motility.
Osmotic diarrhea is caused by poor absorption of certain molecules, which leads to an excessive amount of solutes in the intestinal lumen. The extra solutes cause fluid retention due to osmosis, which is when water moves from intestinal cells across semipermeable membranes into the lumen so that solute concentrations are equal on both sides.
One example of this is lactose intolerance, where there’s a deficiency in the brush border enzyme lactase in the small intestine, which breaks down lactose. The excess lactose stays in the lumen and pulls water into the intestinal lumen leading to diarrhea.
Osmotic diarrhea will resolve when the affected person stops ingesting the causative product.
In secretory diarrhea, there’s increased secretion or decreased absorption of ions like chloride or bicarbonate. This is most commonly caused by bacterial endotoxins, like cholera toxin released by vibrio cholerae.
This toxin increases the secretion of chloride and bicarbonate ions in the small intestine, while inhibiting Sodium ion absorption. These ions build up and cause an osmotic effect, sucking more water into the lumen from the surrounding tissues.
What differentiates it from osmotic diarrhea is that symptoms remain, even with decreased oral intake.
Inflammatory diarrhea is caused by immune mediated damage to the epithelial lining of the large and small intestine, which impairs their absorptive ability for nutrients and water.
It could be caused by inflammatory bowel diseases like crohn's disease and ulcerative colitis, or infections, most commonly by viruses like rotavirus, and bacteria like salmonella, shigella, or E.coli.
In diarrhea associated with deranged motility, like in irritable bowel syndrome, there’s increased enteric nervous system activation, which leads to increased frequency of peristalsis. This pushes the chyme through the intestines too quickly, resulting in less time for water and nutrients to be absorbed.
Most cases of diarrhea is self limiting and no treatment is necessary.
In more severe cases, the primary treatment should always be to replace the fluids and electrolytes to prevent problems like dehydration, hypotension, hypokalemia, and metabolic acidosis. Pharmacotherapy for diarrhea should be used when there’s a risk of developing these symptoms.
Antidiarrheal medications can reduce the frequency and severity of diarrhea, but they do not address the underlying cause.
Classes of drugs that help to treat diarrhea include adsorbents, opioids, and anticholinergics.
Let’s start with adsorbents, which are medications that can bind to diarrhea-causing toxins, so they cannot act on the cells of the GI tract. This includes bismuth, cholestyramine, kaolin, and pectin.
Kaolin is a clay used to make porcelain china, and it’s usually combined with pectin, a plant polysaccharide. Both substances are indigestible compounds that adsorb bacterial toxins and water in the GI tract, leading to increased stool bulk and viscosity. However, they should be avoided within two to three hours of taking other medications since they could bind to them in the GI tract and prevent their absorption.
Bismuth is given with salicylate and is commonly known as Pepto-Bismol. This medication is usually used as an antacid for the treatment of dyspepsia. The antidiarrheal mechanism of action of bismuth is poorly understood, but is thought to have anti-secretory, anti-inflammatory, and antimicrobial effects. It’s commonly used for the treatment and prevention of traveler's diarrhea.
Cholestyramine is a sticky and insoluble resin that’s often given as a cholesterol lowering agent. This medication binds to bile acids and certain bacterial toxins.
Bile salt in the small intestine emulsifies fats, making them easier to absorb, and stimulates both water and electrolyte secretion, which can lead to secretory diarrhea.
Cholestyramine binds to the toxins and bile salts to form insoluble complexes that are excreted with the feces.
For side effects, bismuth salicylate causes ototoxicity and can lead to tinnitus or hearing loss. It can also cause the tongue and stool to turn black.
Cholestyramine can cause discoloration and erosion of the teeth if kept in the mouth for too long, and it also reduces the absorption of fat soluble vitamins like vitamin A, D, E, and K.