Difenoxin

Antidiarrheals decrease intestinal peristalsis, which is usually increased when the patient has diarrhea. Examples of these drug s include difenoxin with atropine (Motofen), diphenoxylate witii atropine (Lomotil), and loperamide (Imodium). 

C30H32N2O2 9 5-30-0) see Difenoxin [4l -[4a,5p,6p(/f )J]-3-[(diphenoxyphosphinyl)oxy]-6-(l-hydroxycthyl)-4-methyl-7-oxo-l azabicyclo[3.2.0]hept-2-enc-2-carboxylic acid (4-nitrophenyl) ester... 

Dexivacaine, 95 DBxnorgBstrel acetime, 152 Diabetes, 116 Diamocaine, 336 Diapamide, 93 Diaveridine, 302 Diazepam, 452 Diazoxide, 395 Dibenzepin, 424, 471 DichloroisopTTOterenol, 106 Diclofenac, 70 Dicyanamide, 21 Dieckmann cyclization, 72 Difenoximide, 331 Difenoxin, 331 Diflucortolone, 192 Diflumidone, 98 Diflunisal, 85, 86 Difluoromethylene groups, from ketones, 196 Difluprednate, 191 Dihydrocodeinone, 318 Dihydropyridine synthesis, 283... 

Pharmacology Difenoxin is an antidiarrheal agent chemically related to meperidine. Atropine sulfate is present to discourage deliberate overdosage. 

Difenoxin manifests its antidiarrheal effect by slowing intestinal motility. The mechanism of action is by a local effect on the Gl wall. 

Difenoxin is the principal active metabolite of diphenoxylate and is effective at one-fifth the dosage of diphenoxylate. 

Pharmacokinetics Difenoxin is rapidly and extensively absorbed orally. Mean peak plasma levels occur within 40 to 60 minutes. Plasma levels decline to less than 10% of their peak values within 24 hours and to less than 1 % of their peak values within 72 hours. This decline parallels the appearance of difenoxin and its metabolites in the urine. Difenoxin is metabolized to an inactive hydroxylated metabolite. The drug and its metabolites are excreted, mainly as conjugates, in urine and feces. 

Hypersensitivity to difenoxin, atropine, or any of the inactive ingredients jaundice. 

Difenoxin hydrochloride with atropine sulfate is not innocuous strictly adhere to dosage recommendations. Overdosage may result in severe respiratory depression and coma, possibly leading to permanent brain damage or death. 

Fiuid and eiectroiyte baiance The use of this drug does not preclude the administration of appropriate fluid and electrolyte therapy. Dehydration, particularly in children, may further influence the variability of response and may predispose to delayed difenoxin intoxication. Drug-induced inhibition of peristalsis may result in fluid retention in the colon, and this may further aggravate dehydration and electrolyte imbalance. 

Atropine A subtherapeutic dose of atropine has been added to difenoxin to discourage deliberate overdosage. A recommended dose is not likely to cause prominent anticholinergic side effects, but avoid in patients in whom anticholinergic drugs are P.833... 

Drug abuse and dependence Addiction to (dependence on) difenoxin is theoretically possible at high dosage. Therefore, do not exceed recommended dosage. 

Pharmacokinetics Bioavailability of tablet vs liquid is approximately 90%. Diphenoxylate is rapidly, extensively metabolized to diphenoxylic acid (difenoxine), the active major metabolite. Elimination half-life is approximately 12 to 14 hours. An average of 14% of drug and metabolites are excreted over 4 days in urine, 49% in feces. Urinary excretion of unmetabolized drug is less than 1% difenoxine plus its glucuronide conjugate constitutes approximately 6%. 

Difenoxin is a metabolite of diphenoxylate with antidiarrheal effects similar to the parent drug. Loperamide Imodium) is a piperidine derivative of diphenoxylate, which acts both at the level of the gut and also in the CNS to reduce GI motility. Its use as an antidiarrheal and its potency are similar to those of diphenoxylate. 

Diphenoxylate and its metabolite, difenoxin, are not used for analgesia but for the treatment of diarrhea. They are scheduled for minimal control (difenoxin is Schedule IV, diphenoxylate Schedule V see inside front cover) because the likelihood of their abuse is remote. The poor solubility of the compounds limits their use for parenteral injection. As... 

Oral 262 mg caplets, chewable tablets 130, 262, 524 mg/15 mL suspension Difenoxin (Motofen)... 

Opioid receptor binding Diphenoxylate and its active metabolite difenoxine (Niemegeers et al., 1972) has a high affinity and selectivity for the p-type of opioid receptor. 

Niemegeers, C.J., Lenaerts, F.M., Janssen, P.A. Difenoxine (R 15403), the active metabolite of diphenoxylate (R 1132). 2. Difneozine, a potent, orally active and safe antidiarrheal agent in rats, Arzneimittelforschung 1972, 22, 516-518. 

Opioid derivatives Difenoxine Motofen1 2 mg initially, 1 mg after each loose stool or every 3-4 hrs... 

Commercial products often combine difenoxine or diphenoxylate [an opioid] with atropine [an anticholinergic]. 

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