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.

It’s important to note that these medications are typically used to treat mild to moderate diarrhea; therefore, they should not be used in individuals with severe illness, bloody diarrhea, or high fever because they can mask or exacerbate the underlying condition.

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.

So, osmotic diarrhea that is caused by lactose intolerance will resolve when the affected person stops ingesting the causative product, such as milk or yogurt.

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 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 are 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.

These medications include 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 absorb bacterial toxins and water in the GI tract, leading to increased stool bulk and viscosity.

Bismuth is given in the form of bismuth subsalicylate, which is commonly known as Pepto-Bismol.

This medication is usually used as an antacid for the treatment of dyspepsia; but it can be also used with metronidazole and tetracycline for Helicobacter pylori eradication.

This combination is also known as BMT (Bismuth subsalicylate, Metronidazole, Tetracycline) regimen!

The antidiarrheal mechanism of action of bismuth is poorly understood, but it 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, but it can be also used to treat diarrhea in individuals with bile acid malabsorption.

These individuals can’t absorb bile acids properly, therefore excessive quantities of bile acids in the lumen stimulate both water and electrolyte secretion, subsequently causing secretory diarrhea. Cholestyramine binds to certain bacterial toxins and bile salts to form insoluble complexes that are excreted with the feces.

For side effects, bismuth subsalicylate can cause the tongue and stool to turn black.

In addition, since it contains salicylate, it is associated with ototoxicity, such as hearing loss and tinnitus.