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Information about Diphenoxylate

Diphenoxylate is synthetic opioid that primarily affects opiate receptors in the intestine and is used to treat diarrhea.


Liver safety of Diphenoxylate

Diphenoxylate has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.

Mechanism of action of Diphenoxylate

Diphenoxylate (dye” fen ox’ i late) is a synthetic piperidine derivative that acts as a mild opiate receptor agonist (predominant µ type receptors), but is used largely for the treatment of diarrhea rather than pain. Diphenoxylate is similar to loperamide and is not structurally related to morphine or codeine, and has minimal euphoric or analgesic effects, largely because it is given in low doses and in fixed combination with atropine. Diphenoxylate acts as a potent opiate agonist in the intestine and reduces intestinal motility, causing a slowing of intestinal transport and increased resorption of water and electrolytes, actions that are helpful in treating diarrhea. Typically, low doses of atropine are added to diphenoxylate to prevent abuse and excessive intake.

FDA approval information for Diphenoxylate

Diphenoxylate in combination with atropine was approved for use in the United States in 1960 and is still widely used to treat acute infectious and nonspecific diarrhea caused by gastroenteritis.

Dosage and administration for Diphenoxylate

Diphenoxylate with atropine is available as tablets 2.5 mg of diphenoxylate with 0.025 mg of atropine and as a solution of similar concentration in 5 mL generically and under the brand name Lomotil. The usual dose in adults is 5 mg four times a day for until diarrhea is controlled, followed by 2.5 mg up to four times daily as needed. Chronic therapy is not recommended.

Side effects of Diphenoxylate

Side effects of diphenoxylate include abdominal bloating and pain, nausea and vomiting and constipation. Because there is systemic absorption, diphenoxylate can also cause central nervous system opioid effects such as confusion, drowsiness, euphoria, dizziness, headache, and respiratory depression. Rare side effects include hypersensitivity reactions, pancreatitis and paralytic ileus. Diphenoxylate with atropine is classified as a controlled substance schedule V, indicating that it has a minimal potential for abuse. Diphenoxylate is available by prescription only.

Full and partial opiod agonists:

Opiate antagonists:

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