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Nature Reviews. Gastroenterology &... Aug 2015Diarrhoeal disease remains a major health burden worldwide. Secretory diarrhoeas are caused by certain bacterial and viral infections, inflammatory processes, drugs and... (Review)
Review
Diarrhoeal disease remains a major health burden worldwide. Secretory diarrhoeas are caused by certain bacterial and viral infections, inflammatory processes, drugs and genetic disorders. Fluid secretion across the intestinal epithelium in secretory diarrhoeas involves multiple ion and solute transporters, as well as activation of cyclic nucleotide and Ca(2+) signalling pathways. In many secretory diarrhoeas, activation of Cl(-) channels in the apical membrane of enterocytes, including the cystic fibrosis transmembrane conductance regulator and Ca(2+)-activated Cl(-) channels, increases fluid secretion, while inhibition of Na(+) transport reduces fluid absorption. Current treatment of diarrhoea includes replacement of fluid and electrolyte losses using oral rehydration solutions, and drugs targeting intestinal motility or fluid secretion. Therapeutics in the development pipeline target intestinal ion channels and transporters, regulatory proteins and cell surface receptors. This Review describes pathogenic mechanisms of secretory diarrhoea, current and emerging therapeutics, and the challenges in developing antidiarrhoeal therapeutics.
Topics: Antidiarrheals; Bacterial Infections; Chloride Channels; Cystic Fibrosis Transmembrane Conductance Regulator; Diarrhea; Gastroenteritis; Gastrointestinal Motility; Humans; Intestinal Absorption; Lysophospholipids; Molecular Targeted Therapy; Potassium Channel Blockers; Probiotics; Receptors, Calcium-Sensing; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers; Solute Carrier Family 12, Member 2; Virus Diseases
PubMed: 26122478
DOI: 10.1038/nrgastro.2015.111 -
Recent Patents on Inflammation &... 2019Travelers' diarrhea is the most common travel-related malady. It affects millions of international travelers to developing countries annually and can significantly... (Review)
Review
BACKGROUND
Travelers' diarrhea is the most common travel-related malady. It affects millions of international travelers to developing countries annually and can significantly disrupt travel plans.
OBJECTIVE
To provide an update on the evaluation, diagnosis, treatment, and prevention of traveler's diarrhea.
METHODS
A PubMed search was completed in Clinical Queries using the key term "traveler's diarrhea". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. Patents were searched using the key term "traveler's diarrhea" from www.freepatentsonline.com.
RESULTS
Between 10% and 40% of travelers develop diarrhea. The attack rate is highest for travelers from a developed country who visit a developing country. Children are at particular risk. Travelers' diarrhea is usually acquired through ingestion of food and water contaminated by feces. Most cases are due to a bacterial pathogen, commonly, Escherichia coli, and occur within the first few days after arrival in a foreign country. Dehydration is the most common complication. Pretravel education on hygiene and on the safe selection of food items is important in minimizing episodes. For mild travelers' diarrhea, the use of antibiotic is not recommended. The use of bismuth subsalicylate or loperamide may be considered. For moderate travelers' diarrhea, antibiotics such as fluoroquinolones, azithromycin, and rifaximin may be used. Loperamide may be considered as monotherapy or adjunctive therapy. For severe travelers' diarrhea, antibiotics such as azithromycin, fluoroquinolones, and rifaximin should be used. Azithromycin can be used even for the treatment of dysentery whereas fluoroquinolones and rifaximin cannot be used for such purpose. Recent patents related to the management of travelers' diarrhea are discussed.
CONCLUSION
Although travelers' diarrhea is usually self-limited, many travelers prefer expedient relief of diarrhea, especially when they are traveling for extended periods by air or ground. Judicious use of an antimotility agent and antimicrobial therapy reduces the duration and severity of diarrhea.
Topics: Anti-Bacterial Agents; Azithromycin; Bismuth; Dehydration; Developing Countries; Dysentery; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Food Contamination; Health Knowledge, Attitudes, Practice; Humans; Loperamide; Organometallic Compounds; Patient Education as Topic; Salicylates
PubMed: 31084597
DOI: 10.2174/1872213X13666190514105054 -
Molecules (Basel, Switzerland) Aug 2020Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their... (Review)
Review
Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.
Topics: Analgesics, Opioid; Codeine; Drug Misuse; Humans; Loperamide; Nonprescription Drugs
PubMed: 32867117
DOI: 10.3390/molecules25173905 -
American Family Physician Sep 2015The Centers for Disease Control and Prevention estimates that each year, one in six Americans will experience a foodborne illness. The most common causes in the United...
The Centers for Disease Control and Prevention estimates that each year, one in six Americans will experience a foodborne illness. The most common causes in the United States are viruses, such as norovirus; bacteria, such as Salmonella, Escherichia coli, Campylobacter, and Listeria; and parasites, such as Toxoplasma gondii and Giardia. Resources are available to educate consumers on food recalls and proper handling, storage, and cooking of foods. Diagnosis and management of a foodborne illness are based on the history and physical examination. Common symptoms of foodborne illnesses include vomiting, diarrhea (with or without blood), fever, abdominal cramping, headache, dehydration, myalgia, and arthralgias. Definitive diagnosis can be made only through stool culture or more advanced laboratory testing. However, these results should not delay empiric treatment if a foodborne illness is suspected. Empiric treatment should focus on symptom management, rehydration if the patient is clinically dehydrated, and antibiotic therapy. Foodborne illnesses should be reported to local and state health agencies; reporting requirements vary among states.
Topics: Anti-Infective Agents; Antidiarrheals; Antiemetics; Blood Chemical Analysis; Colic; Diagnosis, Differential; Diarrhea; Disease Outbreaks; Feces; Fluid Therapy; Food Contamination; Foodborne Diseases; Humans; Microbiological Techniques; Parasitology; Polymerase Chain Reaction; Population Surveillance; United States; Vomiting
PubMed: 26371569
DOI: No ID Found -
Revista Espanola de Enfermedades... Jan 2020Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes:... (Review)
Review
Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antidiarrheals; Antimetabolites; Azathioprine; Biological Products; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Diarrhea; Humans; Loperamide; Malabsorption Syndromes; Mesalamine; Methotrexate; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Time Factors
PubMed: 31880163
DOI: 10.17235/reed.2019.6655/2019 -
The New England Journal of Medicine Sep 2020The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting.
METHODS
We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration.
RESULTS
The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration.
CONCLUSIONS
Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).
Topics: Antidiarrheals; Child, Preschool; Diarrhea; Diarrhea, Infantile; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Male; Medication Adherence; Vomiting; Zinc
PubMed: 32966722
DOI: 10.1056/NEJMoa1915905 -
PloS One 2018Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children.
METHODS
Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison.
RESULTS
A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate].
DISCUSSION/CONCLUSION
Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk.
PROSPERO REGISTRATION
CRD42015023778.
Topics: Antidiarrheals; Bayes Theorem; Child; Diarrhea; Gastroenteritis; Humans; Loperamide; Network Meta-Analysis; Prebiotics; Probiotics; Saccharomyces boulardii; Treatment Outcome; Zinc
PubMed: 30517196
DOI: 10.1371/journal.pone.0207701 -
The Medical Clinics of North America Mar 2016Traveler's diarrhea (TD) is the most common travel-related illness, and it can have a significant impact on the traveler. Pretravel consultation provides an excellent... (Review)
Review
Traveler's diarrhea (TD) is the most common travel-related illness, and it can have a significant impact on the traveler. Pretravel consultation provides an excellent opportunity for the clinician to counsel the traveler and discuss strategies such as food and water hygiene, vaccinations, and medications for prophylaxis or self-treatment that may decrease the incidence and impact of TD. Postinfectious sequelae, such as postinfectious irritable bowel syndrome, reactive arthritis, and Guillain-Barre syndrome, may develop weeks or months after return.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antidiarrheals; Arthritis, Reactive; Bismuth; Dehydration; Diarrhea; Female; Fluid Therapy; Foodborne Diseases; Guillain-Barre Syndrome; Humans; Immunocompromised Host; Irritable Bowel Syndrome; Organometallic Compounds; Pregnancy; Probiotics; Risk Factors; Salicylates; Travel; Travel Medicine; Vaccines; Waterborne Diseases
PubMed: 26900116
DOI: 10.1016/j.mcna.2015.08.017 -
BMJ Clinical Evidence Apr 2015It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home. (Review)
Review
INTRODUCTION
It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (empirical), antibiotics plus antimotility agents, antimotility agents, bismuth subsalicylate, diet, oral rehydration solutions, and racecadotril for travellers' diarrhoea.
Topics: Anti-Bacterial Agents; Antidiarrheals; Bismuth; Diarrhea; Diet; Fluid Therapy; Humans; Organometallic Compounds; Salicylates; Thiorphan; Travel-Related Illness
PubMed: 25928418
DOI: No ID Found -
CMAJ : Canadian Medical Association... Jun 2017
Topics: Antidiarrheals; Arrhythmias, Cardiac; Humans; Loperamide; Substance-Related Disorders
PubMed: 28606977
DOI: 10.1503/cmaj.161421