Antidiarrheals

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Introduction0:00–0:39

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.

Physiology0:39–1:45

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.

Pathology1:45–5:02

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.

Adsorbents5:02–8:03

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.
Also, in children recovering from a viral infection like the flu, salicylate can cause a life-threatening encephalopathy called Reye’s syndrome; therefore it should be avoided in the pediatric population.
Cholestyramine is associated with gastrointestinal disturbances, such as abdominal pain, anorexia, nausea, and flatulence; but it can also cause discoloration and erosion of the teeth if kept in the mouth for too long.
Also, it reduces the absorption of fat-soluble vitamins like vitamin A, D, E, and K; therefore individuals should take these vitamins at least 4 hours before cholestyramine.
Finally, kaolin and pectin can cause constipation and they should be avoided within two to three hours of taking other medications since they could bind them in the GI tract and prevent their absorption.
The second class of medications that help with diarrhea are certain opioids like loperamide and diphenoxylate that have a low risk of developing dependence.

Opioids8:03–10:11

Opioids work by stimulating the mu (μ) or delta (δ) opioid receptors found in the neurons of the enteric nervous system and smooth muscle, which decreases peristalsis.
Loperamide has high antidiarrheal and antisecretory effects; but a very low penetrance in the central nervous system. So, there’s a low addictive potential and therefore lower likelihood of abuse.
Loperamide has been shown to be effective in chronic diarrhea and it also stands for the first-line treatment of traveler’s diarrhea.
Diphenoxylate has some penetrance in the central nervous system so there’s a higher addictive potential; therefore, it’s typically given in the form of preparations that contain an anticholinergics like atropine.
Atropine prevents and discourages the abuse due to unpleasant side effects like dry mouth, blurred vision, sedation, hyperthermia, and urinary retention.
An additional benefit of atropine is that it also inhibits intestinal motility and secretion, providing a synergistic effect when combined with an opioid.
Now, as far as the side effects go, loperamide and diphenoxylate can cause constipation, abdominal cramps, drowsiness, dizziness, and paralytic ileus.
It’s important to note that concomitant use of these opioids and other CNS depressants, like benzodiazepines, barbiturates, and alcohol, should be avoided due to increased risk of CNS depression.
Also, these medications can cause toxic megacolon in individuals with ulcerative colitis; while diphenoxylate can induce hepatic coma in individuals with hepatic or renal impairment.
On the other hand, loperamide is associated with torsades de pointes and cardiac arrest when used in higher doses than recommended.
Finally, these medications are contraindicated in children below the age of 4; while loperamide is also contraindicated in individuals with QT prolongation!Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharmacology facts!

Memory Palace10:11–12:52

For the adsorbent medications, let’s have a stressed out businessman for bismuth salicylate. His stressful job gave him gastritis, which can also be cured by this medication.
For side effects, let’s give him a black tongue from all the coffee he needs to drink. He’s wearing headphones, representing ototoxicity, so he won’t be distracted by his kid who’s eating a loaf of rye bread for reye’s syndrome.
To help him relax, he ordered a pecan bonsai tree, representing pectin, and it came in a chinese porcelain pot, for kaolin.
This will help you remember these 2 are given together. Let’s have a watering can next to the bonsai tree to help you remember that aside from absorbing toxins, it also absorbs water and serves as a bulking agent.
Next to the tree, is the box it was delivered in, which is full of packing peanuts made of styrofoam, for cholestyramine.
There’s a salt shaker full of green salt inside the box to help you remember it also binds to bile salt. For side effects, the letters A, D, E, and K are written on the box to help you remember the decreased absorption of these vitamins, and next to the box is a pair of brown colored dentures to help you remember its effect on the teeth.
Now the businessman is thinking about his dream vacation, which like all good vacations, will represent the medications that slows intestinal motility.
There’s an island with a tropical palm tree to represent atropine. For the side effects, let’s have a guy taking a nap with a face mask on, representing sedation and visual disturbance.
He’s fanning himself since he’s experiencing hyperthermia, and there’s a tall empty glass next to him to help you remember dry mouth and urinary retention.
For the opioids, let’s use some exotic animals. There’s a dolphin with ox horns for diphenoxylate, and it’s right by the palm tree to help you remember it’s given together with atropine to reduce opioid abuse.
Next, is an antelope, for loperamide, that’s standing off on its own, since it can be used alone. For side effects, let’s put a large ice cube by the dolphin, since diphenoxylate causes more side effects.
It contains a brain, lungs, and the small intestine to help you remember decreased activity in these organs. ##SummaryAll right, as a quick recap, diarrhea has four main causes, which include osmotic, secretory, inflammatory, and diarrhea associated with deranged motility.

Review12:52–13:36

Primary treatment for diarrhea should always be oral rehydration with electrolytes. There are three main classes of medications for severe or chronic diarrhea, which include adsorbents, opioids, and anticholinergics.
Adsorbents bind to toxins that cause diarrhea and often have other beneficial effects, such as absorbing water or bile salts.

Mind Map13:36–13:48

Opioids and anticholinergics decrease intestinal motility, and are often given together to reduce the likelihood of opioid abuse.
pause the video so you can test yourself to see what you remember Stay tuned for the answers after the