ANTIDIARRHEAL AGENTS

ANTIDIARRHEAL AGENTS

Diarrhea

Abnormal frequent passage of loose stool 

or

Abnormal passage of stools with increased frequency, fluidity, and weight, or with increased stool water excretion.

Diarrhea is the condition of having three or more loose or liquid bowel movements per day. 

Diarrhea can be caused by 

An increased osmotic load within the intestine (resulting in retention of water within the lumen) 

Excessive secretion of electrolytes and water into the intestinal lumen.

Exudation of protein and fluid from the mucosa.

Altered intestinal motility resulting in rapid transit (and decreased fluid absorption). 

Pharmacotherapy of diarrhea should be reserved for patients with significant or persistent symptoms. 

Nonspecific antidiarrheal agents typically do not address the underlying pathophysiology responsible for the diarrhea; their principal utility is to provide symptomatic relief in mild cases of acute diarrhea.

Mechanism of Action

Adsorbents

Coat the walls of the GI tract

Bind to the causative bacteria or toxin, which is then eliminated through the stool.

Examples: bismuth subsalicylate (Pepto-Bismol), kaolin-pectin, attapulgite.

Clays such as kaolin (a hydrated aluminum silicate) and other silicates such as attapulgite (magnesium aluminum disilicate) bind water avidly and also may bind enterotoxins. 

However, this effect is not selective and may involve other drugs and nutrients; hence, these agents are best avoided within 2–3 hours of taking other medications. 

A mixture of kaolin and pectin (a plant polysaccharide) is a popular over-the-counter remedy (kaolin-pectin) and may provide useful symptomatic relief of mild diarrhea.

Side Effects

Adsorbents

Constipation, dark stools

Confusion, twitching

Hearing loss, tinnitus, metallic taste, blue gums

Mechanism of Action

Anticholinergics

Decrease intestinal muscle tone and peristalsis of GI tract

Result: slowing the movement of fecal matter through the GI tract

Examples: Atropine

Side Effects 

Anticholinergics

Urinary retention, hesitancy, impotence

Headache, dizziness, confusion, anxiety, drowsiness

Dry skin, rash, flushing

Blurred vision, photophobia, increased intraocular pressure

Antimotility and Antisecretory Agents

OPIOIDS

Opioids continue to be widely used in the treatment of diarrhea. 

They act principally through either µ- or δ- opioid receptors on enteric nerves, epithelial cells, and muscle.

These mechanisms include effects on intestinal motility (µ receptors), intestinal secretion (δ receptors), or absorption (µ and d receptors).

Commonly used antidiarrheals such as Diphenoxylate, and Loperamide act principally via peripheral µ-opioid receptors and are preferred over opioids that penetrate the CNS.

Loperamide

Loperamide a Piperidine butyramide derivative with µ-receptor activity, is an orally active antidiarrheal agent. 

The drug is 40–50 times more potent than morphine as an antidiarrheal agent and penetrates the CNS poorly. 

It increases small intestinal and mouth-to-cecum transit times. 

Loperamide also increases anal sphincter tone, an effect that may be of therapeutic value in some patients who suffer from anal incontinence. 

In addition, loperamide has antisecretory activity against cholera toxin and some forms of Escherichia coli toxin

Diphenoxylate and Difenoxin

Diphenoxylate and its active metabolite Difenoxin (diphenoxylic acid) are related structurally to meperidine. 

As antidiarrheal agents, diphenoxylate and difenoxin are somewhat more potent than morphine. 

Both compounds are extensively absorbed after oral administration, with peak levels achieved within 1–2 hours.

Both drugs can produce CNS effects when used in higher doses (40–60 mg/day) and thus have potential for abuse and/or addiction.