Introduction to bowel management
Victoria A. Lane, Richard J. Wood, Carlos A. Reck-Burneo, Marc A. Levitt in Pediatric Colorectal and Pelvic Surgery, 2017
Loperamide is an opioid receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the intestine, but does not affect the central nervous system. The mechanism of action is to reduce the activity of the myenteric plexus, which in turn decreases the tone of the circular and longitudinal smooth muscles of the intestinal wall, thus increasing the time that the digested material remains in the large intestine, allowing for more water to be reabsorbed. Loperamide also suppresses gastrocolic reflex, thereby decreasing colonic mass movements.Diphenoxylate and atropine combinations (e.g., Lomotil). Diphenoxylate is an opioid agonist and acts as an anti-diarrheal agent by slowing intestinal contractions and peristalsis (atropine is added to prevent overdose as this causes tachycardia).
Criteria For Evaluating Physical And Psychic Dependence And Overall Abuse Potential Of Drugs In Man
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
Another characteristic that the addict demands is the rapid development of morphine- or heroinlike effects when the drug is injected intravenously. Failure of a morphine-like drug to induce such an effect promptly is illustrated by diphenoxylate (Lomotil®). This compound is so insoluble in water that it must be dissolved in pure propylene glycol, and if even a drop of water is present in the syringe, the diphenoxylate will be precipitated out of the solution. Apparently, when diphenoxylate is injected into the vein, it precipitates in the bloodstream and is absorbed by the central nervous system at such a slow rate that the addict does not recognize significant effect for at least 20 minutes. Such a drug would have relatively low abuse potential on two grounds: (1) for practical purposes, the addict is precluded from injecting it, since water is his only readily available solvent, and (2) he would be dismayed by the lack of effect when it is injected intravenously, even though quite good morphine effects are obtained after 30 to 45 minutes.
Diarrhea in Short Bowel Syndrome
John K. DiBaise, Carol Rees Parrish, Jon S. Thompson in Short Bowel Syndrome Practical Approach to Management, 2017
Antimotility agents play an important role in slowing intestinal transit time and promoting absorption of nutrients by prolonging mucosal contact time, thus decreasing stool output. These agents include loperamide, diphenoxylate-atropine, codeine phosphate, and tincture of opium. These medications should generally be administered 30–60 minutes prior to meals for maximal benefit. Titration of the dosage is recommended until the desired effect or maximal amount is achieved. Adjustments can be made every 3–5 days. Patients occasionally benefit from using a combination of these medications. Loperamide and diphenoxylate-atropine are typically the first-line option due to their efficacy and benign side effect profile. Multiple formulations are available. While liquid formulations are available, most are sorbitol-based elixirs that may actually aggravate the diarrhea. Loperamide capsules can be opened and ingested with food or, if tablets are used, they can be crushed in an effort to enhance absorption. Typically, two to four tablets up to four times a day can be utilized. Excessive use of diphenoxylate-atropine is associated with anticholinergic side effects, including cardiovascular symptoms such as tachycardia; patients will require counseling to avoid them. Although abuse potential exists, it remains low with antimotility agent use in SBS.
Ileostomy diarrhea: Pathophysiology and management
Published in Baylor University Medical Center Proceedings, 2020
Kyle M. Rowe, Lawrence R. Schiller
Antimotility agents include loperamide, diphenoxylate/atropine, codeine, morphine, and tincture of opium. Loperamide and diphenoxylate are synthetic mu-opioid agonists with antimotility effects, particularly in the small bowel.63 Atropine is combined with diphenoxylate to discourage abuse; its anticholinergic properties may supplement its antidiarrheal effects slightly. As loperamide has limited ability to cross the blood-brain barrier, it has fewer central and anticholinergic adverse effects than diphenoxylate/atropine or more potent opioids. Loperamide has been shown in several randomized trials to decrease the output of established ileostomies by 22% to 30%.64–67 Studied doses have varied, but the standard dose is 4 mg four times per day before meals and at bedtime.
Emerging oral VEGF inhibitors for the treatment of renal cell carcinoma
Published in Expert Opinion on Investigational Drugs, 2019
Lea Stitzlein, PSS Rao, Richard Dudley
Diarrhea is a frequently reported adverse effect with sunitinib, pazopanib, and cabozantinib, all of which are preferred regimens from the NCCN guidelines for treating mRCC. Upwards of 50% of patients on either of these inhibitors experience diarrhea, which may be severe in nature. Multiple mechanisms, including the abundance of VEGFR expression in the gastric mucosa, are thought to be responsible for the non-tumor gastrointestinal cell inhibition resulting in diarrhea [34,66]. Interestingly, clinical studies conducted to date involving both anlotinib and vorolanib have indicated a decreased incidence in, or milder diarrhea, indicative of a more favorable gastrointestinal toxicity profile [47,67]. Special attention should be paid to the structure-activity relationships of anlotinib and vorolanib and future development of VEGFR inhibitors should strive to emulate their favorable GI adverse effect profile. Attenuating drug-induced diarrhea is of paramount importance for several reasons including dramatic improvements in patient quality of life, decreased risk of dehydration, electrolyte imbalance, and avoidance of fatigue and cardiovascular related complications of diarrhea in an already vulnerable patient population. Strategies to treat diarrhea-related adverse effects often involve the administration of an additional pharmacological agent (loperamide or diphenoxylate/atropine), however, this may increase the risk of additional adverse effects [68].
Zhizhu decoction alleviates slow transit constipation by regulating aryl hydrocarbon receptor through gut microbiota
Published in Pharmaceutical Biology, 2023
Yong Wen, Yu Zhan, Shiyu Tang, Fang Liu, Rong Wu, Pengfei Kong, Qian Li, Xuegui Tang
STC is a disease characterized by delayed colon transit, 24 h defecation volume, fecal water content, and ITR can be used as its representative diagnostic indicators (Jani and Marsicano 2018). Studies have shown that compound diphenoxylate is a common method for modeling constipation (Deng et al. 2021). In the present study, it revealed that after continuous intragastric administration of compound diphenoxylate, the defecation volume, fecal water content, and ITR of mice were significantly decreased than those of the control group, and there was a certain degree of pathological damage to the colon, indicating the successful establishment of STC model. As a common Chinese medicine compound, ZZD is beneficial to functional dyspepsia, and this study found that ZZD significantly improved intestinal motility and alleviated colon injury in the STC mouse model. In addition, ZZD significantly increased the expressions of Ach, SP, 5-HT, and decreased the expression of VIP in the colon of STC mice, activated the AHR signaling pathway, and changed the composition of the gut microbiota. Therefore, it could be considered that alleviation of intestinal motility injury in STC mice by ZZD may be associated with the activation of the AHR signaling pathway by gut microbiota to regulate intestinal neurotransmitters.
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