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We describe three cases of CPPD crystal deposition disease in elderly patients whose main symptom was fever. Misdiagnosis of such cases is possible because of the similarity of the clinical picture to that of septic fever. The probable mechanisms causing the fever are discussed. There was spectacular improvement in these patients after a high dose of oral colchicine and loperamide and no relapse was observed during the long term administration of colchicine in a conservative dose together with supplementary magnesium.
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Many drugs have been known to cause diarrhea, although their mechanism of action has not been well described. Determining the etiology of drug-induced diarrhea depends on careful history taking to identify the offending agent. Drug-induced diarrhea may be classified as watery, inflammatory, fatty diarrhea. Treatment may vary depending on this classification and usually includes withdrawal of the offending drug. However, in some cases, diarrhea may resolve with continued use or through nonspecific agents, such as loperamide.
Spironolactone, a commonly used mineralocorticoid receptor antagonist, has been reported to potentiate the effect of morphine in the rat. The aim of this study was to investigate the effects of spironolactone on morphine antinociception and tissue distribution.
Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing.
The effects of an antidiarrhoeal agent, loperamide, were studied using isolated guinea pig taenia coli. Loperamide in concentrations ranging from 10(-7) M inhibited the cholinergic, contractile responses induced by electrical transmural stimulation, nicotine and serotonin, and the nonadrenergic, relaxing responses induced by electrical transmural stimulation and nicotine. However, the adrenergic response to perivascular nerve stimulation was not affected by these concentrations. The inhibitory effects of loperamide were not reversed by washing with a drug-free solution. Morphine (10(-6 M to 10(-5) M) also inhibited both cholinergic and nonadrenergic responses, but the effect was reversible. Naloxone (1o(-6) M) attenuated the inhibitory effects of both drugs. Unlike morphine, loperamide in concentrations higher than 5 x 10(-6) M relaxed the strips and reduced the contractile response to acetylcholine noncompetitively, and these effects were not blocked by naloxone. These results suggest that loperamide at low concentrations acts selectively on the opiate receptors located in both cholinergic and nonadrenergic nerves and at higher concentrations also acts directly on smooth muscle thus producing relaxation of the intestinal tone.
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PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and International Society of Travel Medicine congress abstracts (2003-2009) were searched to identify relevant publications.
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Ninety patients were included in this prospective double-blind trial comparing loperamide with placebo over 5 weeks. The two groups were characterized and compared with healthy controls (n = 33), matched by age and sex. Demographic, clinical, and biochemical data were recorded.
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Surgical approach with full tickness excision and immediate skin-grafting and regular follow-up demonstrated effective to treat GCA and to minimize disease recurrence.
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All patients with biopsy-proven lymphocytic colitis evaluated at our institution between January 1, 1997, and December 31, 1999, were identified. Clinical features on presentation and treatment outcomes were abstracted from the medical records.
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A total of 20 drugs were tested for their efficacy in the treatment of infections involving the two major acanthocephalans infesting rainbow trout in European trout farms. In in vitro experiments, the antidiarrhoeic loperamid and the well-known anthelminthic drug niclosamide showed the best efficacy. Worms treated with loperamid contracted the posterior end of their body, in which severe necrosis of the tegument caused the death of the worms. In in vivo experiments, loperamid was the most efficacious drug: 50 mg/kg given to rainbow trout on 3 consecutive days led to a complete cure. According to preliminary tolerance tests in water baths, the toxicity of this drug is low as compared with that of niclosamide, which is very toxic. Thus, loperamid can be recommended as the drug of choice for therapy of acanthocephalan infections in fish.
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During the summers of 2002 to 2003, 176 US adults recently arrived in Guadalajara, Mexico were enrolled in a prospective, double-blinded, randomized trial of the treatment of acute diarrhea. Subjects received single doses (1,000 or 500 mg) of azithromycin or a single 500 mg dose of azithromycin plus loperamide. Subjects gave a pre- and post-treatment stool sample for analysis and maintained daily diaries of symptoms and passage of stools.
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We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers.
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describe the multidisciplinary management and outcome in pediatric patients with intestinal failure.
The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to management and prevention of loperamide-induced cardiac arrhythmias.
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The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 220.127.116.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs--that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.
Our results showed that CDE produced a significant dose-dependent protection against castor oil-induced diarrhea and intestinal fluid accumulation. On the other hand, we showed that diarrhea was accompagned by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa hydrogen peroxide (H2O2) and free iron levels. Importantly, we showed that chamomile pre-treatment abrogated all these biochemical alterations.
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The effect of a hot water extract of black tea (Camellia sinensis (L.) O. Kuntze, Theaceae) on upper gastrointestinal transit and on diarrhoea was investigated employing conventional rodent models of diarrhoea. Black tea extract was found to possess antidiarrhoeal activity in all the models of diarrhoea used. Naloxone (0.5 mg/kg i.p.) significantly inhibited the antidiarrhoeal activity of the extract as well as loperamide, thus indicating a role of the opioid system in the antidiarrhoeal activity of the extract.
Seventeen healthy volunteers had a total of 23 PET scans with (11)C-dLop at baseline and after increasing doses of tariquidar (2, 4, and 6 mg/kg intravenously). A subset of subjects received PET with (15)O-H(2)O to measure cerebral blood flow. Brain uptake of (11)C-dLop was quantified in 2 ways. Without blood data, uptake was measured as area under the time-activity curve in the brain from 10 to 30 min (AUC(10-30)). With arterial blood data, brain uptake was quantified with compartmental modeling to estimate the rates of entry into (K(1)) and efflux from (k(2)) the brain.
This review focuses on two areas: the first on describing the peripheral opioidergic system, and the second on the review of the current state of development of peripherally active opioid receptor agonists with theirpotential clinical applications.
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Only one of the ten studies in our review supported the finding that inhibition of P-glycoprotein is associated with clinically relevant signs or symptoms of central nervous system (CNS) depression/opioid toxicity of loperamide. None of the 25 spontaneous case reports of interest were suggestive of signs or symptoms of CNS depression/opioid toxicity due to coadministration of loperamide and a P-glycoprotein inhibitor or substrate.
The simulated patient methodology was used in all 21 community pharmacies in a north-eastern German city with a population of about 63,000. Four scenarios related to self-medication for acute diarrhoea were developed and used in all pharmacies (total: 84 visits). Two scenarios were direct product-based requests for loperamide (scenario 1: a 74-year old woman with diabetes and hypertension; scenario 3: a 30-year old man with no primary disease). Scenario 2 and 4 were symptom-based requests asking for medicine for acute diarrhoea (scenario 2: a 74-year old woman with diabetes and hypertension; scenario 4: a 30-year old man with no primary disease). The assessment sheet included 9 objective items relating to the pharmacological advice to avoid a subjective evaluation by the mystery shoppers (e. g., the friendliness of the customer contact). Simulated patient visits were conducted covertly by five untrained female master students. After evaluation of the data every pharmacy received an individual performance feedback to encourage behavioural change and improve counselling quality.
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Perifosine (NSC 639966) is a synthetic, substituted heterocyclic alkylphosphocholine that acts primarily at the cell membrane targeting signal transduction pathways. Early clinical trials were limited because of dose-limiting gastrointestinal toxicity, and parenteral dosing of this class of agents is not possible because of their hemolytic properties; therefore, related compounds with an improved therapeutic index were developed. Toxicity was minimized and efficacy improved by using a loading dose/maintenance dose schedule, and therefore, this schedule was carried into clinical trials. This phase I trial enrolled 42 patients with incurable solid malignancies. The starting doses were 100 mg p.o. x four doses (every 6 hours) load followed by a 50 mg p.o. once daily maintenance dose with escalation of either component in successive dose levels. No treatment related deaths occurred. The maximum-tolerated dose was determined to be 150 mg p.o. x four doses load and 100 mg p.o. once daily maintenance. Dose-limiting toxicities such as nausea, diarrhea, dehydration, and fatigue were seen early during the loading phase and were surmountable with the use of prophylactic 5-HT3 receptor antagonists, dexamethasone, and loperamide. Toxicities during the chronic phase were difficult to manage and, given that pharmacokinetic data showed biologically active serum concentrations (based on preclinical data), raised the question of less frequent maintenance dosing. Pharmacokinetic data confirmed the maintenance of stable drug levels with chronic dosing and the long half-life. One partial response was seen, as were multiple patients with stable disease beyond course 2. These results suggest perifosine activity in sarcoma and perhaps renal cell carcinoma (stable disease in two patients who continued for 6 and 14 courses), thus justifying additional investigation of this agent in a phase II sarcoma trial.
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Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature. The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea. Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days. The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool. Results: Ofloxacin and loperamide were well tolerated. Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001). Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001). Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours. Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.
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Epilepsy is characterized by spontaneous recurrent seizures and represents one of the most frequent neurological diseases, affecting about 60 million people worldwide. The cellular and neurocircuit bases of epilepsy are poorly understood. Constipation is a common gastrointestinal disorder characterized by symptoms such as straining, hard stool, and infrequent defecation. Population-based studies have shown that the prevalence of constipation is up to 30% of the population in developed countries. The causal link between seizure and constipation is a common belief among patients and physicians, but there are no scientific data to support this association. The current investigation evaluated the effects of constipation induced by loperamide (a peripheral μ-opioid receptor agonist without effect on central nervous system receptors) and clidinium (a quaternary amine antimuscarinic agent with reduced central nervous system effects) on two different seizure models of mice: (1) myoclonic, clonic, and generalized tonic seizures and death induced by intraperitoneal administration of pentylenetetrazole and (2) clonic seizure threshold induced by intravenous infusion of pentylenetetrazole. We demonstrated that the measured intestinal transit (%intestinal transit) decreased after loperamide or clidinium treatment for 3days. Constipation in mice which was induced by loperamide or clonidine caused a decrease in threshold to clonic seizure in the intravenous pentylenetetrazole seizure model. Moreover loperamide- or clidinium-induced constipation decreased latencies to, clonic, and tonic seizures and death in the intraperitoneal pentylenetetrazole model of mice. Serum ammonia levels were slightly elevated in both loperamide- and clidinium-treated mice. In conclusion, loperamide- or clidinium-induced constipated mice are more prone to seizure which might confirm the belief of patients and physicians about constipation as a trigger of seizure.
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Gastrointestinal adverse effects contribute significantly to drug attrition as well as reduced patient compliance. Determination of gastrointestinal liability early in a compound's preclinical development would be a valuable tool. We evaluated the non-invasive faecal pellet method in the rat, assessed the feasibility of adding the endpoint to other study types and investigated correlation with the charcoal meal method.
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Wood creosote, the principal ingredient in Seirogan, has a long history as a known gastrointestinal microbicidal agent. When administered orally, the intraluminal concentration of wood creosote is not sufficiently high to achieve this microbicidal effect. Through further animal tests, we have shown that antimotility and antisecretory actions are the principal antidiarrheal effects of wood creosote. Wood creosote inhibits intestinal secretion induced by enterotoxins by blocking the Cl(-) channel on the intestinal epithelium. Wood creosote also decreases intestinal motility accelerated by mechanical, chemical, or electrical stimulus by the inhibition of the Ca(2+) influx into the smooth muscle cells. In this overview, the antimotility and antisecretory effects of wood creosote are compared with those of loperamide. Wood creosote was observed to inhibit stimulated colonic motility, but not normal jejunal motility. Loperamide inhibits normal jejunal motility, but not stimulated colonic motility. Both wood creosote and loperamide inhibit intestinal secretion accelerated by acetylcholine. Wood creosote was found to have greater antisecretory effects in the colon than loperamide. Based upon these findings, we conclude that the antidiarrheal effects of wood creosote are due to both antisecretory activity in the intestine and antimotility in the colon, but not due to the microbicidal activity as previously thought. Wood creosote was found to have no effects on normal intestinal activity. These conclusions are supported by the results of a recent clinical study comparing wood creosote and loperamide, which concluded that wood creosote was more efficacious in relieving abdominal pain and comparable to loperamide in relieving diarrhea.
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To compare the efficacy and safety of a loperamide hydrochloride-simethicone combination product with those of loperamide alone, simethicone alone, and placebo in treating acute diarrhea with gas-related abdominal discomfort.
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With vigilant monitoring and aggressive therapy for cancer treatment-induced diarrhea, particularly in patients with early warning signs of severe complications, morbidity and mortality may be reduced.