ジフェノキシラート

WHITE CRYSTALLINE POWDER; ODORLESS; PH OF SATURATED SOLN ABOUT 3.3. /DIPHENOXYLATE HYDROCLORIDE/

CHEMICALLY RELATED TO MEPERIDINE

DIPHENOXYLATE MAY POTENTIATE ACTIONS OF BARBITURATES, OPIATES, & OTHER CNS DEPRESSANTS.

Concomitant administration of amphetamine has been reported to enhance analgesics effects of meperidine and its cogeners.

As with most opiates in current use, therapy with diphenoxylate with atropine has not been linked to serum enzyme elevations. There have been no convincing cases of idiosyncratic acute, clinically apparent liver injury attributed to diphenoxylate. The reason for its lack of hepatotoxicity may relate partially to the low doses used. What diphenoxylate that is absorbed is metabolized in the liver.

Diphenoxylate is an opiate receptor agonists that stimulate mu receptors in GI to decrease the peristalsis and constrict the sphincters. 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 may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.

Coma, dry skin and mucous membranes, enlarged pupils of the eyes, extremely high body temperature, flushing, involuntary eyeball movement, lower than normal muscle tone, pinpoint pupils, rapid heartbeat, restlessness, sluggishness, suppressed breathing

SIDE EFFECTS ARE USUALLY MINOR & INCL NAUSEA ... DIZZINESS, VOMITING, PRURITUS, SKIN ERUPTION, INSOMNIA, & ABDOMINAL CRAMPS. NUMBNESS OF EXTREMITIES, HEADACHE, BLURRING OF VISION, SWELLING OF GUMS, & GENERAL MALAISE HAVE ALSO BEEN REPORTED. /DIPHENOXYLATE HYDROCHLORIDE/

MILD RESPIRATORY DIFFICULTY SEEN IN 5 TO 6 HR PROGRESSED TO APNEA & CYANOSIS AFTER 8 HR. ... OTHER DERANGEMENTS, EG, LOSS OF BLADDER TONE & DIMINUTION OF LIGHT REFLEX, RESEMBLED SIDE EFFECTS OF ATROPINE.

HAS A DEFINITE CONSTIPATING EFFECT IN MAN ... AT HIGH DOSES (40 TO 60 MG) ... SHOWS TYPICAL OPIOID ACTIVITY, INCL EUPHORIA, SUPPRESSION OF MORPHINE ABSTINENCE, & MORPHINE-LIKE PHYSICAL DEPENDENCE AFTER CHRONIC ADMIN.

ALTHOUGH DOSE RECOMMENDED FOR 2-YR-OLD CHILD IS 5 MG/DAY, SEVERE POISONING HAS RESULTED FROM ACCIDENTAL INGESTION OF ONLY 4 TIMES THIS DOSE. /DIPHENOXYLATE HYDROCHLORIDE/

For more Human Toxicity Excerpts (Complete) data for DIPHENOXYLATE (10 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Diphenoxylate

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

Supportive Care: Patients with signs of atropinism or CNS depression should be admitted. For urinary retention, catheterization may be required. Intensive care monitoring of vital signs (pulse rate, respiratory rate and depth, blood pressure), fluid balance (intake and output), level of consciousness, pupil size, and arterial blood gases must be continually recorded to guide patient status with regard to naloxone administrationand fluid infusions (cerebral and pulmonary edema). This should be maintained for 24 hr.

Elimination Enhancement: Forced diuresis, hemodialysis, hemoperfusion, and peritoneal dialysis are not useful in removing diphenoxylate or its metabolites, in view of the high volume of distribution.

Antidotes: Respiratory depression and coma are indications for initiating naloxone. The dosage in the adult is 0.4-2.0 mg iv (1-5 ampules) repeated every few minutes up to a total of 10 mg; in the child, the initial dose is 0.01-0.1 mg/kg iv followed by an additional dose of 0.1 mg/kg as required. If no response /results/ consideration must be given to exclusion of diphenoxylate-atropine, propoxyphene, or methadone as the causative agent. If a response /results/, multiple doses of naloxone every 20-45 min may be required, since the half-life of naloxone and an opioid antagonist may be effective for only 45-70 min. If frequent iv boluses are required to maintain adequate respiration and consciousness, give continuous iv naloxone infusion. Add 4-8 mg of naloxone (from a 10 ml multiple dose vial containing 0.4 mg/ml) to each liter of D5W or similar fluid and infuse at the rate of 100 ml/hr (0.4-0.8 mg naloxone/hr).

Gut Decontamination: Admin of an emetic is undesirable because of the rapidity with which the patient may become apneic and drowsy, increasing the possibility if aspiration. Activated charcoal may be of /utility/. Caution must be exercisedin using induced emesis if there is respiratory depression, depression of consciousness, obtundation, or loss of gag reflex. In such cases, gastric lavage with endotracheal intubation would be safter.

For more Antidote and Emergency Treatment (Complete) data for DIPHENOXYLATE (6 total), please visit the HSDB record page.

73312P173G

DIPHENOXYLATE

Established Pharmacologic Class [EPC] - Antidiarrheal

Diphenoxylate is an Antidiarrheal.

Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.

Miscellaneous agents found useful in the symptomatic treatment of diarrhea. They have no effect on the agent(s) that cause diarrhea, but merely alleviate the condition.

90%

Fecal/renal elimination; less than 1% eliminated unchanged in urine.

In one study in fasting individuals, diphenoxylate hydrochloride was well absorbed from the GI tract following oral administration of an alcoholic solution of the drug without atropine sulfate. Peak plasma diphenoxylate concentrations occurred about 2 hours following administration of the drug. In a crossover bioavailability study of Lomotil tablets and oral solution, the bioavailability of the tablets was approximately 90% that of the solution; following an oral dose of four 2.5 mg tablets, an average peak plasma concentraton of diphenoxylic acid (an active metabolite of diphenoxylate) of 163 ng/ml occurred within about 2 hours. Diphenoxylate had an onset of action within 45 minutes to 1 hour and a duration of action of 3-6 hours. /Diphenoxylate hydrochloride/

Diphenoxylate is distributed into milk.

Diphenoxylate is rapidly and extensively metabolized to diphenoxylic acid, an active metabolite. The drug is also metabolized to hydroxydiphenoxylic acid. Diphenoxylate metabolites and their conjugates are slowly excreted, principally in feces via bile; lesser amounts are excreted in urine. Less than 1% is exceted unchanged in urine.