Disease relevance of DIPHENOXYLATE

• Diphenoxylate and pancreatitis [1].
• Approximately equal numbers discontinued each preparation; poor control and central-nervous-system side effects were the usual reasons for stopping diphenoxylate and codeine, and abdominal pain and constipation for stopping loperamide [2].
• Loperamide is probably superior to diphenoxylate in providing symptomatic control of chronic diarrhoea such as that associated with chronic inflammatory bowel disease or following gastrointestinal surgery [3].
• Respiratory depression recurred 13 to 24 hours after the ingestion in 7 cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate [4].
• Use of routine diphenoxylate hydrochloride prophylaxis was tolerated without ileus or gastrointestinal obstruction clinically [5].

Psychiatry related information on DIPHENOXYLATE

• Short-course diphenoxylate hydrochloride for treatment of methadone withdrawal symptoms [6].

High impact information on DIPHENOXYLATE

• Double-blind cross-over study comparing loperamide, codeine and diphenoxylate in the treatment of chronic diarrhea [2].
• Efficacy data suggest that loperamide is more effective than the prescription drug diphenoxylate and an over-the-counter bismuth subsalicylate preparation [7].
• On the diphenoxylate arm, 15/28 patients were required to discontinue pelvic radiotherapy; on the octreotide arm, 6/33 patients were required to discontinue pelvic radiotherapy for an average of 1.89 +/- 0.5 and 0.45 +/- 0.2 days, respectively (p = 0.003) [8].
• Diphenoxylate-induced hypoxia was the major problem and was associated with slow or fast respirations, hypotonia or rigidity, cardiac arrest, and in 3 cases cerebral edema and death [4].
• The antidiarrheal opiates loperamide, fluperamide, diphenoxylate and fetoxylate inhibited binding of [3H]nitrendipine to membranes from guinea-pig cerebral cortex with Ki values of 0.5 to 10 microM [9].

Biological context of DIPHENOXYLATE

• Effects of E prostaglandins, diphenoxylate and morphine on intestinal motility in vivo [10].
• A comparative evaluation of charcoal and chromium oxide used as inert, nonabsorbable markers revealed that chromium oxide may be the marker of choic in GI transit studies in laboratory animals since it does not influence the bioavailability of diphenoxylate hydrochloride [11].
• Diphenoxylate shared with morphine the capacity to stimulate circular muscle contractions which correlated with the appearance of spike potentials on the BER [10].

Anatomical context of DIPHENOXYLATE

• Cellular uptake and efflux and transcellular transport were all determined using Caco-2 cells after exposure to loperamide or diphenoxylate, with or without a range of efflux inhibitors [12].

Associations of DIPHENOXYLATE with other chemical compounds

• In vitro adsorption of diphenoxylate hydrochloride on activated charcoal and its relationship to pharmacological effects of drug in vivo. I [11].
• The mechanism of the gastrointestinal motility effects of diphenoxylate and morphine in preventing E prostaglandin (PG) diarrhea was investigated [10].
• Activated charcoal modified the bioavailability of diphenoxylate hydrochloride in vivo [11].
• Determination of diphenoxylate hydrochloride and atropine sulfate in combination drug formulations by liquid chromatography [13].
• LPA and DP, which are used therapeutically for diarrhea, did not inhibit the effect of ST enterotoxin; MP and HC, known inhibitors of cholera enterotoxin, and two adrenergic agents (PR and PTM) had no effect on ST-induced secretory activity [14].

Gene context of DIPHENOXYLATE

• Diphenoxylate transport, however, showed little sign of P-gp-mediated efflux [12].
• Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter [15].
• Naloxone is the narcotic antagonist of choice, and should be used in all cases where suspected diphenoxylate poisoning leads to respiratory depression or coma [16].
• Other drugs, such as histamine H2-receptor blockers, pseudoephedrine, and atropine/diphenoxylate should be used with caution [17].

Analytical, diagnostic and therapeutic context of DIPHENOXYLATE

• A double-blind study of 20 patients with ulcerative colitis during treatment with diphenoxylate 5 mg three times daily and placebo is reported [18].
• Because of its action in rendering the gut atonic, removal of diphenoxylate by gastric lavage is mandatory, even in patients admitted at least 24 hours after drug ingestion [16].
• One quarter of these patients preferred codein phosphate or diphenoxylate and about one half a low fat diet, either alone or in combination with the above mentioned drugs [19].
• The effect of loperamide and diphenoxylate on diarrhoea following jejuno-ileostomy for morbid obesity was investigated in 27 patients by means of a randomized fixed sample size, three-period cross-over trial [20].

References