Sun-Dianox Mechanism of Action

Pharmacology: Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. After a 5-mg oral dose of carbon-14 labelled diphenoxylate hydrochloride in ethanolic solution was given to three healthy volunteers, an average of 14% of the drug plus its metabolites was excreted in the urine and 49% in the feces over a four-day period. Urinary excretion of the unmetabolized drug constituted less than 1% of the dose, and diphenoxylic acid plus its glucuronide conjugate constituted about 6% of the dose. In a 16-subject crossover bioavailability study, a linear relationship in the dose range of 2.5 to 10 mg was found between the dose of diphenoxylate hydrochloride and the peak plasma concentration, the area under the plasma concentration-time curve, and the amount of diphenoxylic acid excreted in the urine. The average peak plasma concentration of diphenoxylic acid following ingestion of four 2.5 mg tablets was 163 ng/ml at about 2 hours, and the elimination half-life of diphenoxylic acid was approximately 12 to 14 hours.
Atropine is readily absorbed from the gastrointestinal tract. It is rapidly cleared from the blood and is distributed throughout the body. It crosses the blood-brain barrier.
It is incompletely metabolised in the liver and is excreted in the urine as unchanged drug and metabolites. A half-life of about 4 hours has been reported.
In animals, diphenoxylate has a direct effect on circular smooth muscle of the bowel that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate hydrochloride may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.
Atropine, a naturally occurring alkaloid, is an anticholinergic agent. It acts by competitive inhibition of the actions of acetylcholine on muscarinic receptors. Vagal influences on the gastrointestinal tract are partially inhibited by atropine. Hence, the motor activity in the stomach and small and large intestines is reduced to treat diarrhea.