Loperamide

In castor oil challenged rats, low doses of loperamide inhibit diarrhea and normalize intestinal propulsion. Unlike other opioids, loperamide is devoid of central opiate-like effects, including blockade of intestinal propulsion, up to the highest subtoxic oral dose. Nevertheless, the antidiarrheal action of loperamide can be considered to be -opiate receptor mediated, only a fewin vitro effects at rather high concentrations being not naloxone-reversible. There is little evidence that interactions with intestinal opiate receptors directly change epithelial cell function. When secretory stimuli increase mucosal tension, however, loperamide may reverse the elevated hydrostatic tissue pressure that opposes normal absorption. This antisecretory effect at the mucosal level is accompanied by motor effects when loperamide reaches the myenteric -opiate receptors. At therapeutic doses for the treatment of acute diarrhea, it is likely that the mucosal effect prevails.     

Effects of the prodrug loperamide oxide,loperamide, and placebo on jejunal motor activity

This crossover, double-blind study investigated the effects of single oral doses of the prodrug loperamide oxide, which is reduced gradually to loperamide in the intestine, and loperamide on jejunal motor activity in 12 fasting healthy men. Five minutes after a phase III of the migrating motor complex (MMC), 2 mg loperamide oxide, 4 mg loperamide oxide, 4 mg loperamide, or placebo were administered. Thereafter, motor activity 10–30 cm aborad the ligament of Treitz was recorded with five catheter orifices at 3-cm intervals over 4 hr. Number of contractions and area under curve increased significantly with 4 mg loperamide and 4 mg loperamide oxide, the increases with loperamide oxide occurring more gradually. Placebo and 2 mg loperamide oxide had no discernible effects. With both 4 mg loperamide and 4 mg loperamide oxide, phase I of the MMC was slightly prolonged and phase II and the time from drug administration to the onset of the first phase III slightly shortened. The percentage of aborally propagated contractions in phase II increased with all active treatments, whereas the occurrence of phases III was not altered.Presented in poster form at the European Digestive Disease Week, Vienna, Austria, June 5–9, 1990Supported by Janssen Pharmaceutica, Beerse, Belgium.     

Stimulation of gastrointestinal motility by loperamide in dogs

The effects of loperamide on gastrointestinal motility were investigated in conscious fasted dogs chronically fitted with strain-gauge transducers on the antrum, the jejunum, and the colon. Oral administration of loperamide (0.1 mg/kg) induced, after a delay of 20–30 min, a long-lasting (8–12 hr) stimulation of gastrointestinal motility associated with a disorganization of the cyclic activity at the three levels investigated. These effects were reproduced by a subcutaneous administration at the same dose and were antagonized by previous intravenous administration of naloxone or a quaternary opiate antagonist. Intracolonic administration (0.1 mg/kg) stimulated, after a delay of 20–30 min, colonic motility only. Intracerebroventricular loperamide (1 g/kg) induced a long-lasting (15–20 hr) inhibition of the gastric motility and a short (2-hr) disorganization of the jejunal motor profile. These data show that oral loperamide stimulates gastrointestinal motility in dogs and involves peripheral opiate receptors.     

Randomized trial of loperamide versus dose escalation of octreotide acetate for chemotherapy-induced diarrhea in bone marrow transplant and leukemia patients

This study compares maximal daily doses of loperamide to escalating doses of continuous intravenous (Cl) octreotide acetate in bone marrow transplant (BMT) and leukemia patients. A total of 36 patients were enrolled in the study. Of these, all were evaluable for intention to treat, and 31 were evaluable for initial response. Based on intent to treat at the initial 48 hr, patients receiving loperamide had a higher complete response rate (86% vs. 45%, P = 0.033) than did those who received octreotide. By treatment analysis (patients who actually received the drug), patients receiving loperamide had a higher complete response rate (92% vs. 56%, P = 0.0448) than did those who received octreotide at the 150 μg dosage level. Additional octreotide patients eventually achieved a CR at a higher dosage level (78%). Loperamide at maximal doses of 4 mg po q6h is more effective than octreotide 150 μg Cl in treating diarrhea following chemotherapy in BMT and leukemia patients. Higher doses of octreotide may be required in a significant number of patients not responding to lower doses. Following chemotherapy, BMT and leukemia patients who developed ≧600 ml of stool volume in a 24-hr period were randomized to receive loperamide 4 mg po q6h or octreotide 150 μg mixed in hyperalimentation solution or normal saline and administered Cl. Patients were assessed at 48 hr intervals for decrease in stool volume from baseline. Complete response (CR) was defined as ≧50% from baseline stool volume (BSV). Patients receiving octreotide who did not achieve a CR at 48 hr were dose escalated by doubling the dose to a maximum of 2,400 μg with evaluations at 48 hr intervals. Patients receiving loperamide who did not achieve a CR at 48 hr had treatment discontinued.     

Healing of gastric body ulcer with gastroprotective versus antisecretory treatment

The aim of this study was to compare the healing effect of a gastroprotective agent and antisecretory drugs in gastric body ulcer where failure of the mucosal defense might be an important factor. Eighty-five patients with benign gastric ulcer were divided into four groups: treated with antacids (I), cimetidine (II), ranitidine (III), and colloidal bismuth subcitrate (De-Nol) (IV). Endoscopically confirmed complete healing was achieved in 57, 61, and 63% in groups I, II, and III, respectively, and in 88% in group IV (P<0.05). Gastric secretion did not change significantly. Relapses during the next three years occurred several times more frequently in groups I, II and III than in group IV.Helicobacter pylori was positive in about half the relapsing patients in groups I, II, and III but negative in those of group IV. It is concluded that De-Nol treatment of gastric body ulcer was more efficient than antisecretory drugs both initially and in reducing relapses.     

A blind, randomized comparison of racecadotril and loperamide for stopping acute diarrhea in adults

AIM: Racecadotril is a specific enkephalinase inhibitor that exhibits intestinal antisecretory activity without affecting intestinal transit. Loperamide is an effective anti-diarrheal agent, but it usually induces constipation. This study is to compare the efficacy, safety, and tolerability of racecadotril versus loperamide in the outpatient treatment of acute diarrhea in adults. METHODS: A two-center, randomized, parallel-group, single-blind study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg thrics daily) and loperamide (2.0 mg 2 twics daily) in 62 adult patients suffering from acute diarrhea. The main efficacy criterion used was the duration of diarrhea after beginning the treatment (in hours). Other signs and symptoms were also evaluated. RESULTS: The clinical success rates for these anti-diarrheal treatments were 95.7% and 92.0% for racecadotril and loperamide respectively. Patients on racecadotril had a median duration of diarrhea of 19.5 h compared with a median of 13 h for patients on loperamide. Rapid improvement in anal burn and nausea was found for each drug. However, more patients on loperamide suffered from reactive constipation (29.0% vs 12.9%). Itching, another adverse event was notably higher in the racecadotril group (28.6% vs 0%). With regard to other adverse events, the two medications showed similar occurrence rates and similar concomitant medication usage rates. CONCLUSION: Racecadotril and loperamide are rapid, equally effective treatments for acute diarrhea in adults, but loperamide treatment is associated with a higher incidence of treatment-related constipation.     

Treatment of chronic diarrhoea: loperamide versus ispaghula husk and calcium

Twenty-five patients with chronic diarrhoea were included in an open, randomized crossover trial comparing the effect of loperamide with ispaghula and calcium. Nineteen patients completed both treatments. Before treatment the median number of daily stools was 7 (range, 4-13), stool consistency was loose in all, and urgency was present in 16 out of 19 patients. Both treatments halved stool frequency, but with regard to urgency and stool consistency ispaghula and calcium was significantly better. A combination of ispaghula and calcium seems to be a cheap and effective alternative to conventional treatment of chronic diarrhoea. Moreover, side effects were minimized.     

Symptomatic treatment of acute infectious diarrhoea: loperamide versus placebo in a double-blind trial

One hundred and twelve patients with acute infectious diarrhoea were entered in a double-blind randomised study in order to compare loperamide with a placebo. Of 82 evaluable patients, 38 received loperamide and 44 placebo for a maximum of 5 days. There were no significant differences in the number of loose stools during the first day of treatment, in the total number of tablets taken or in the total duration of the period of diarrhoea between the two treatment groups. The loperamide-treated patients had significantly fewer loose stools during the observation period of 5 days than did the placebo treated patients, median five vs. seven, a difference of little clinical importance. Excretion of bacterial pathogens was followed weekly in 13 of the loperamide treated patients (median 35.5 days) and in 18 of the placebo treated patients (median 22.5 days). This difference in the duration of excretion was not significant.     

Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection

Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea.We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization.There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4–10] vs 5 [3–7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 10⁹ cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710–0.872]).Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.     

Inflammation revisited: inflammation versus resolution of inflammation following myocardial infarction

Myocardial infarction (MI) is the main cause for the progression of the left ventricle towards congestive heart failure. The optimal healing after MI requires timely induction and resolution of inflammation. Primarily, there have been a number of strategies applied to inhibit the post-MI inflammation but approaches that focus on the resolution of inflammation have sparsely been used in the treatment of heart failure. The early attempts to inhibit post-MI inflammation resulted in adverse outcomes that were realized in heart failure trials. We provide here an overview on the cyclooxygenase (COX)- and lipoxygenase (LOX)-derived lipid mediators that are either impairing or resolving the post-MI inflammation. With the evolution of lipidomics there has been emerging novel bioactive-specialized lipid mediators that promise to resolve chronic inflammation rather than promoting inhibition. The current review is focused on post-MI immune cells kinetics and the unexplored array of lipid mediators that are coordinated by COX and LOX. Thus, an emphasis on COX and LOX poses key questions and potential for the development of novel targets in the heart failure treatment strategy. This updated dynamic approach aims to fuse basic pre-clinical discoveries and translational bioactive lipid-based resolvin discoveries that could be potentially used in the clinic for the treatment of heart failure.     

Allergen tolerance versus the allergic march: The hygiene hypothesis revisited

In addition to genetics, several environmental variables appear to impact allergic risk. Meta-analyses of epidemiologic studies presented in this article demonstrate a correlation between specific ambient exposures (eg, livestock, pets, endotoxin, and unpasteurized milk ingestion) and reduced allergic risk during childhood. Additional laboratory investigations discussed in this review characterized the intrinsic immunostimulatory activities of living environments. Considered together, results of these investigations suggest a novel paradigm by which early-life home exposures to microbial products and other allergen-nonspecific immunostimulants modify allergic risk.     

Reverse cholesterol transport revisited: contribution of biliary versus intestinal cholesterol excretion

Reverse cholesterol transport (RCT) is usually defined as high-density lipoprotein-mediated transport of excess cholesterol from peripheral tissues, including cholesterol-laden macrophages in vessel walls, to the liver. From the liver, cholesterol can then be removed from the body via secretion into the bile for eventual disposal via the feces. According to this paradigm, high plasma high-density lipoprotein levels accelerate RCT and hence are atheroprotective. New insights in individual steps of the RCT pathway, in part derived from innovative mouse models, indicate that the classical concept of RCT may require modification.     

感染性腹泻新病原体研究动态

通过对国内外感染性腹泻新病原体研究动态的阶段性回顾，使我们至少获得下列启迪：(1)感染性腹泻病与经济文化、战乱及社会动荡相伴；(2)感染性腹泻病是无国界的，特别像霍乱这样的国际检疫传染病更是全人类公害；(3)从理论上讲，感染性腹泻病是完全能够预防和控制的。但实际上因影响因素较多，难度极大。如果我们将彻底控制感染性腹泻病的希望寄托于抗生素、液体疗法和疫苗(菌苗)的研制及应用是不现实的。本文仅感染性腹泻新病原体霍乱、O139、EHEC O157：H7、非Ol群弧菌、弯曲菌、耶尔森菌、病毒性腹泻、SARS胃肠系统合并症、隐孢子虫、难辨羧状芽胞杆菌、革兰阳性棒状杆菌等研究动态做以介绍。     

Scientific evidence versus therapeutic demand: the introduction of the sulfonamides revisited.

Because of recent changes in Federal Food and Drug Administration (FDA) regulations, new medications may now be marketed before completion of rigorous controlled testing. In order to understand the ramifications of this development, it is instructive to recall the introduction of the sulfonamides in the 1930s. The sulfonamides, the first effective antibacterial agents, were marketed in an era of relatively few regulations. Although investigators at times designed controlled trials to evaluate use of the drugs, both researchers and practitioners generally prescribed them for severe infections, despite a lack of conclusive data as to their efficacy. The clinical usefulness of sulfonamides for a given condition often became known through uncontrolled case studies and comparisons with historical control groups. Given the relaxation of FDA regulations, this method of drug evaluation may again become more commonplace.     

布拉氏酵母菌散剂预防支原体肺炎继发腹泻的临床研究

目的研究布拉氏酵母菌散剂预防支原体肺炎继发腹泻的临床疗效。方法以我院收治的123例支原体肺炎患儿为研究对象,随机分成两组,预防组63例,对照组60例。两组均给予抗肺炎支原体及对症支持等治疗,预防组加服布拉氏酵母菌散剂连续治疗至出院,对比两组患儿住院第4天及第7天继发腹泻的发病率,以及腹泻平均持续时间。结果两组患儿继发腹泻发病率比较差异有统计学意义(χ2=6.34,P0.05),腹泻平均持续时间预防组为(62.79±7.61)h,对照组为(72.26±16.36)h,两组比较差异有统计学意义(t=2.95,P0.01)。结论布拉氏酵母菌散剂能够有效降低支原体肺炎继发腹泻的发病率,并能减轻腹泻的严重度,缩短腹泻的持续时间,值得临床推广应用。     

Ethnicity and alcohol/drug use revisited: a framework for future research

Despite the large pool of research findings pertaining to ethnic and racial variations in the use of drugs (including alcohol), the relationship between ethnicity and drug use has not been thoroughly examined. This paper describes some of the major findings regarding ethnic and racial variations in drug use, and examines the methodological limitations of such studies. Moreover, this paper addresses the problem of shortage of theoretical explanations for ethnic variations in drug use. It is argued that the variable of ethnicity has not been properly conceptualized and measured in most studies. Cultural and structural aspects of ethnicity at both the individual and collective levels are examined, and their possible contributions to more rigorous research on the relationship between ethnicity and drug use are discussed.