Loperamide

Aim: To investigate the laxative potentials of aqueous leaf extract of Sida acuta in loperamideinduced constipation in Wistar rats. Methods: Constipation was induced by oral administration of loperamide (3 mg/kg b.wt.). The constipated rats were orally treated daily either with 200, 400, 800 mg/kg body weight per day of the extract or 0.21 mg/kg bisacodyl (reference drug) for 7 days while the normal and constipated control groups received distilled water. The feeding characteristics, body weight, faecal properties and gastrointestinal transit ratio were monitored throughout the study period. Results: There was significant decrease (p < 0.05) between normal and constipated rats in the number of faecal pellets and water content of faecal pellets while there was no significant changes in the feed/ water intake and body weight of rats. Administration of the graded doses of the extract to the constipated rats significantly and dose- dependently normalized (p < 0.05) the number of faecal pellets/ water content of faecal pellets and gastrointestinal ratio compared to the constipated control. Conclusion: The aqueous root extract of Sida acuta possesses laxative activity in loperamide-induced constipated rats.

Irritable bowel syndrome (IBS) is the most common disorder diagnosed by gastroenterologists and one of the more common ones encountered in general practice. The overall prevalence rate is similar (approximately 10%) in most industrialized countries; the illness has a large economic impact on health care use and indirect costs, chiefly through absenteeism. IBS is a biopsychosocial disorder in which 3 major mechanisms interact: psychosocial factors, altered motility, and/or heightened sensory function of the intestine. Subtle inflammatory changes suggest a role for inflammation, especially after infectious enteritis, but this has not yet resulted in changes in the approach to patient treatment. Treatment of patients is based on positive diagnosis of the symptom complex, limited exclusion of underlying organic disease, and institution of a therapeutic trial. If patient symptoms are intractable, further investigations are needed to exclude specific motility or other disorders. Symptoms ...

AbstractThis prospective cohort study describes travelers&#39; diarrhea (TD) and non-TD gastrointestinal (GI) symptoms among international travelers from the Boston area, the association of TD with traveler characteristics and dietary practices, use of prescribed antidiarrheal medications, and the impact of TD and non-TD GI symptoms on planned activities during and after travel. We included adults who received a pre-travel consultation at three Boston-area travel clinics and who completed a three-part survey: pre-travel, during travel, and post-travel (2-4 weeks after return). TD was defined as self-reported diarrhea with or without nausea/vomiting, abdominal pain, or fever. Demographic and travel characteristics were evaluated by χ(2) test for categorical and Wilcoxon rank-sum test for continuous variables. Analysis of dietary practices used logistic generalized estimating equation models or logistic regression models. Of 628 travelers, 208 (33%) experienced TD and 45 (7%) experien...

The Anti-diarrhoeal effect of aqueous extract of Rubia tinctorum L. (Rubiaceae) roots in rodents was examined. At doses 300, 600 and 800 mg/kg aqueous extract protected rats, in a dose-dependent fashion, against castor oil-induced diarrhoeal dropping by 37, 59 and 64% respectively. ...

The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. The standard drug loperamide (5 mg/kg) showed significant (p&lt;0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducin...

We compared the dependence liabilities of therapeutic doses of nufenoxole and loperamide. Ten subjects received 10 mg nufenoxole every 12 hr for 10 days, and 9 others received 4 mg loperamide every 12 hr for 10 days. On the eighth day of drug a sensitive single-blind intravenous naloxone challenge was used to assess dependence liability. After 0.2, 0.4, and 0.6 mg naloxone, pupillary constriction (0.618 to 0.540 cm, p less than 0.005) was measured in subjects receiving nufenoxole, whereas slight dilation (0.596 to 0.622 cm, p less than 0.05) was observed in those receiving loperamide. Trapezius electromyogram activity decreased by 30% for nufenoxole and 12% for loperamide. There were slight decreases in core and skin temperatures (0.06 degrees to 0.12 degrees) in both groups, partly attributable to experimental conditions. Changes in physiologic measurements after naloxone were similar in both groups and not of sufficient importance to suggest physical dependence liability for eithe...

Background Loperamide, a potent opioid, has been used as an in vivo probe to assess P-glycoprotein activity at the blood-brain barrier, because P-glycoprotein inhibition allows loperamide to cross the blood-brain barrier and exert its central opioid effects. In humans, studies with nonselective and moderately potent inhibitors resulted in mild opioid effects but were confounded by the concurrent inhibition of loperamide&#39;s metabolism. The authors studied the effect of the highly selective, potent P-glycoprotein inhibitor tariquidar on loperamide&#39;s central opioid effects. Methods In a randomized, double-blind, crossover study, nine healthy subjects received on 2 study days oral loperamide (32 mg) followed by an intravenous infusion of either tariquidar (150 mg) or placebo. Central opioid effects (pupil diameter, sedation) were measured for 12 h, and blood samples were drawn up to 48 h after drug administration to determine plasma loperamide concentrations and ex vivo P-glycopr...

A simple and sensitive liquid chromatography-tandem mass spectrometric method for quantification of loperamide in human plasma and saliva was developed and validated, and then successfully applied in pharmacokinetic clinical study to investigate and correlate bioavailability of Imodium (R) 2 mg quartet tablet dose in both human plasma and saliva. Loperamide with labeled internal standard was extracted from its biological matrix by methanol as protein direct precipitant in single extraction step. Adequate chromatographic separation for analytes from plasma and saliva matrices was achieved using ACE C18 (50mm x 2.1 mm, 5 mu m) column, eluted by water/methanol/formic acid (30:70:0.1%, v/v), delivered isocratically at constant flow rate of 0.75 ml/min. The method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability according to European guideline, and partial validation was applied on saliva, specificity, matri...

ABSTRACTCoronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ∼30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activit...

The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after or...

Ca2+i signalling is pivotal to sperm function. Progesterone, the best-characterized agonist of human sperm Ca2+i signalling, stimulates a biphasic [Ca2+]i rise, comprising a transient and subsequent sustained phase. In accordance with recent reports that progesterone directly activates CatSper, the [Ca2+]i transient was detectable in the anterior flagellum (where CatSper is expressed) 1–2 s before responses in the head and neck. Pre-treatment with 5 μM 2-APB (2-aminoethoxydiphenyl borate), which enhances activity of store-operated channel proteins (Orai) by facilitating interaction with their activator [STIM (stromal interaction molecule)] ‘amplified’ progesterone-induced [Ca2+]i transients at the sperm neck/midpiece without modifying kinetics. The flagellar [Ca2+]i response was unchanged. 2-APB (5 μM) also enhanced the sustained response in the midpiece, possibly reflecting mitochondrial Ca2+ accumulation downstream of the potentiated [Ca2+]i transient. Pre-treatment with 50–100 μM...

The purpose of our case report is to generate awareness among the providers about the rising abuse of loperamide, which is a readily available nonprescription medication for its opiate-like actions and the risk of severe cardiac complications as a consequence of the same. It is currently becoming a significant concern among the healthcare fraternity due to its increasing abuse owing to its opioid agonistic activity. Our patient was a 32-year-old female who presented to the ED with ventricular dysrhythmias and persistent, prolonged QT interval secondary to excessively high doses of over-the-counter (OTC) loperamide abuse. More and more cases of loperamide abuse and its cardiotoxic potential are being reported in the literature, highlighting the increasing incidence of this problem.