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What is Diphenoxylate?

By Donn Saylor
Updated Mar 03, 2024
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Diphenoxylate is an opioid drug prescribed for the treatment of diarrhea. It is often utilized in conjunction with atropine and sold as the drug Lomotil®. The drug works in the system by slowing peristalsis, the natural muscular contraction and relaxation of the intestine, and, as such, is classified as antiperistaltic drug.

In slowing peristalsis, moisture is drawn from the contents of the intestine, allowing for more solid waste products. This serves as an antidote to the rapid peristalsis action usually triggered by diarrhea, which produces soft or water-like stools. Diphenoxylate also encourages better absorption of nutrients. The drug is derived from meperidine, an analgesic with antispasmodic properties.

By itself, diphenoxylate is an opiate, which means it has psychoactive properties and can be potentially addictive. When atropine is added, as in the case of Lomotil®, the psychoactive characteristics of diphenoxylate in small doses are counteracted, and the drug is, in general, much better tolerated. Larger dosages may still generate the psychoactive properties.

Due to its narcotic capabilities, diphenoxylate is most often prescribed for short-term use. Longer-term usage typically builds a tolerance to the drug, and larger and larger dosages are needed to achieve the anti-diarrheal effect. With significant doses, however, comes the possibility of dependence. Patients are encouraged to taper off high doses of diphenoxylate since withdrawal effects may be acute; a doctor will advise the best methods of tapering-off.

Diphenoxylate may be given in either tablet or liquid form. Bloating and constipation are the most frequently reported side effects. Given the fact that the drug is an opiate, it may also potentially act as a tranquilizer.

This drug has been shown to react negatively with certain antidepressant drugs called monoamine oxidase inhibitors (MAOIs). It also may interact with narcotic pain relievers, sleep aids, or specific anti-seizure medications. Diphenoxylate might not mix well with cough syrups or other cold and flu products that induce sleepiness.

In many countries, diphenoxylate is considered a controlled substance. In Austria, Canada, Germany, and the United States, diphenoxylate is specifically mentioned in drug laws as a potentially dangerous narcotic. With regard to its medical treatment aspects, many countries will allow it to be prescribed by a doctor or prescribed only in conjunction with atropine.

Diphenoxylate, when combined with atropine, is generally taken four times a day. When prescribing this combination, doctors suggest drinking plenty of fluids, especially fluids containing electrolytes. A mild diet may also be necessary to further support the diphenoxylate-atropine combo.

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