How Diphenoxylate Works to Combat Diarrhea
Diphenoxylate is a potent synthetic opioid agonist that works primarily on the opiate receptors within the smooth muscle of the intestinal tract. By binding to these receptors, diphenoxylate inhibits gastrointestinal (GI) motility and slows down the movement of the intestines. This action prolongs the transit time of stool through the gut, allowing the body to absorb more fluid and electrolytes from the intestinal contents, which helps to consolidate stools and reduce the frequency and urgency of bowel movements.
Why is Atropine Combined with Diphenoxylate?
To prevent misuse and overdose, commercial preparations of diphenoxylate (like Lomotil) contain a subtherapeutic dose of atropine, an anticholinergic drug. In normal therapeutic doses, this small amount of atropine does not interfere with the antidiarrheal effect of diphenoxylate. However, if a person attempts to take a significantly higher dose to achieve a euphoric opioid effect, the atropine will cause unpleasant anticholinergic side effects such as dry mouth, blurred vision, and flushing. This helps to deter abuse of the medication.
Indications and Uses of Diphenoxylate
Diphenoxylate is used for the symptomatic management of various forms of diarrhea. It is important to note that it is not recommended for diarrhea caused by certain bacterial infections, such as those from Clostridioides difficile, as slowing intestinal motility could worsen the condition. Specific uses include:
- Acute Diarrhea: This includes nonspecific diarrhea and travelers' diarrhea, where the medication helps to provide symptomatic relief.
- Chronic Diarrhea: Diphenoxylate can be used as an adjunctive treatment for chronic diarrhea, often associated with conditions like inflammatory bowel disease (IBD).
- Irritable Bowel Syndrome (IBS) with Diarrhea: In some cases, diphenoxylate/atropine may be prescribed off-label for diarrhea-predominant IBS when other treatments are not effective.
Important Safety Information and Precautions
Despite its effectiveness, diphenoxylate is a controlled substance and requires a prescription due to its opioid properties and potential for abuse. There are several important safety considerations to be aware of:
Contraindications and warnings
- Children under 6 years: Diphenoxylate is contraindicated in children under 6 years of age due to the risk of severe respiratory depression, which can be fatal. In children ages 6 to 12, it must be used with extreme caution and only in the liquid form. The appropriate amount of the liquid formulation for children in this age range is determined by their weight.
- Infectious Diarrhea: The medication should not be used for diarrhea caused by bacteria that produce toxins (like C. difficile or certain E. coli strains). Slowing the bowel can lead to fluid retention, potentially worsening bacterial proliferation and increasing the risk of complications like toxic megacolon, a life-threatening condition involving the severe swelling of the large intestine.
- Liver Disease: Diphenoxylate should be used with caution in patients with severe liver disease, as it is metabolized in the liver, and impairment can increase the risk of side effects, including hepatic encephalopathy.
- Glaucoma and Urinary Retention: Due to the atropine component, caution is needed in patients with a history of glaucoma or problems with urinary retention.
Potential Drug Interactions
Diphenoxylate can interact with numerous other medications. It is crucial to inform your doctor about all prescription, over-the-counter, and herbal supplements you are taking. Some important interactions include:
- CNS Depressants: Concurrent use with alcohol, barbiturates, benzodiazepines, and other CNS depressants can increase the risk of drowsiness, dizziness, and respiratory depression.
- Monoamine Oxidase Inhibitors (MAOIs): Using diphenoxylate with MAOIs can, in theory, lead to a hypertensive crisis.
- Other Medications: Diphenoxylate can potentiate the effects of other drugs, and caution is needed when combining with certain medications for anxiety, depression, or other conditions.
Diphenoxylate vs. Loperamide Comparison
When treating diarrhea, diphenoxylate is often compared to loperamide (Imodium). While both are synthetic opioids that act on the gut, they have key differences.
| Feature | Diphenoxylate (e.g., Lomotil) | Loperamide (e.g., Imodium) |
|---|---|---|
| Mechanism of Action | Works on opioid receptors in the GI tract to slow motility. Can cross the blood-brain barrier. | Works on opioid receptors in the GI tract to slow motility. Has a lower ability to cross the blood-brain barrier. |
| Controlled Substance | Yes, Schedule V. Contains atropine to discourage abuse. | No. Lower potential for abuse. |
| Availability | Prescription only. | Over-the-counter (OTC) and prescription options. |
| Use in Children | Not for use under 6 years old; liquid formulation only for ages 6–12. | Not recommended for children under 6 years old. |
| Potential for Dependence | Possible with higher-than-prescribed amounts or prolonged use. | Low potential for addiction when used as directed. |
| Cardiovascular Risk | Less common, but overdose can cause tachycardia. | High doses can increase risk of heart rhythm problems (QT prolongation). |
Conclusion
Diphenoxylate is a prescription antidiarrheal drug used to control symptoms of severe diarrhea by slowing intestinal motility. Its combination with atropine is a deliberate measure to prevent abuse. It is crucial for patients to adhere strictly to prescribed dosages and to be aware of the risks, especially when considering its use in children or in patients with certain underlying medical conditions, such as infectious diarrhea or liver disease. As with any medication, discussing your full medical history and current drug regimen with a healthcare provider is essential before starting diphenoxylate. For more detailed information on specific drug precautions, you can consult sources like the MedlinePlus drug information based on information from the National Library of Medicine.
