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Cutaneous manifestations due to drugs used in the treatment of gastrointestinal disorders are multiple and common. Adequate diagnosis is of great importance, bearing in mind that the therapeutic regimen depends on its diagnosis. In this review, we provided an overview of the most common drug-induced skin lesions with a detailed explanation of the disease course, presentation and treatment, having in mind that in recent years, novel therapeutic modalities have been introduced in the treatment of various gastrointestinal disorders, and that incidence of cutaneous adverse reactions has been on the rise.

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BACKGROUND: Gestational reflux is common, affecting up to 80% of pregnant women. Most symptoms will abate during lactation. During both of these periods, interventions used to relieve symptoms focus on a "step-up" methodology with progressive intensification of treatment. This begins with lifestyle modifications. AIM: To provide guidance in the treatment of reflux in pregnancy and lactation, as well as briefly summarising the pathogenesis, clinical presentation and diagnostic workup. METHODS: A comprehensive search, using online databases PubMed and MEDLINE, along with relevant manuscripts published in English between 1966 and 2019 was used. All abstracts were screened, potentially relevant articles were researched, and bibliographies were reviewed. RESULTS: Only a small percentage of relevant drugs are contraindicated for use in pregnancy or while breastfeeding. However, not all drug agents have been extensively evaluated in pregnant women or during the breastfeeding period. Antacids, alginates, and sucralfate are the first-line therapeutic agents. If symptoms persist, any of the H2 RAs can be used except for nizatidine (due to foetal teratogenicity or harm in animal studies). PPIs are reserved for women with intractable symptoms or complicated GERD; all are FDA category B drugs, except for omeprazole, which is a category C drug. CONCLUSIONS: The management of heartburn during pregnancy and lactation begins with lifestyle modifications. In situations where disease severity increases, medical providers must discuss risks and benefits of these medicines with the patient in detail.

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OBJECTIVES: Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. METHODS: MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. RESULTS: Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas [37.2%, 95% confidence interval (CI), 29.0-46.3] and suppositories (44.9%, 95% CI, 28.9-62.3) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR = 4.14, 95% CI, 2.35-7.31), aminosalicylate suppositories (RR = 3.94, 95% CI, 1.26-12.32), and budesonide multimatrix (RR = 1.47, 95% CI 1.08-1.99) had higher histologic remission rates than placebo. Data were lacking for biologics and immunosuppressives. The pooled histologic remission rate for placebo in induction studies was 10.4% (95% CI, 7.1-15.2). Histologic and endoscopic remission correlated strongly (r = 0.66; 95% CI, 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity and corticosteroid use were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates when active-arm data were analyzed. CONCLUSIONS: Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow CIs. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.

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The highest attrition rates during drug development programmes occur at the proof of concept stage. Given the large number of molecules under development for Crohn's disease, a need exists to improve the efficiency of early drug development by fast-tracking promising agents and terminating ineffective ones. Multiple opportunities are available to achieve these goals, including the use of more responsive outcome measures, and the incorporation of sophisticated pharmacokinetic modelling and/or highly specific pharmacodynamic markers into exposure-based dosing regimens and novel trial designs. In this article we review these strategies and propose an integrated paradigm of early drug development in Crohn's disease.

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With the issuance of this final rule, the Administrator of the Drug Enforcement Administration places the substance 5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6-dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxybenzoic acid (eluxadoline), including its salts, isomers, and salts of isomers, into schedule IV of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule IV controlled substances on persons who handle (manufacture, distribute, dispense, import, export, engage in research, conduct instructional activities, or possess) or propose to handle eluxadoline.

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This chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threatening extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod have been grave enough to lead to their withdrawal from many world markets. Awareness and recognition of the neurotoxicity of gastrointestinal drugs is essential to help weigh the benefit of their use against possible adverse effects, even if uncommon. Furthermore, as far as possible, drugs such as metoclopramide and others that can lead to tardive dyskinesias should be used for as short time as possible, with close clinical monitoring and patient education.

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Constipation is a frequently diagnosed gastrointestinal disorder. Symptoms of constipation are common, with the greatest prevalence in the elderly. Evaluation of constipation begins with a detailed medical history and a focused anorectal examination. Diagnostic testing for constipation is not routinely recommended in the initial evaluation in the absence of alarm signs. Key self-management strategies include increased exercise, a high-fiber diet, and toilet training. High-fiber diets can worsen symptoms in some patients who have chronic constipation. Biofeedback is an effective treatment option for patients who have constipation caused by outlet obstruction defecation. A variety of medications are available to remedy constipation.

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Evaluation of the action of various medicines used to treat irritated bowel syndrome from the standpoint of evidence based medicine indicates that most of them (spasmolytics, probiotics, loperamide, aperients) show but low effectiveness. The use of more efficacious preparations (alosterone, cisapride, tegacerode) is associated with serious adverse reactions whereas prucalopride is applied for unregistered indications. It necessitates the development of new drugs with enhanced effectiveness and tolerability.

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This review is concerned with the main classes of medicines stimulating the motor activity of the gastrointestinal tract widely used in clinical practice and studied in clinical trials (dopamine receptor blockers, 5-HT4- and 5-HT1-receptor antagonists, agonists of motilin receptors, antagonists of A type cholecystokinin and opioid receptors, etc.). The necessity of developing new generations of prokinetics is emphasized in order to improve efficiency and safety of therapy with these preparations.

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BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

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INTRODUCTION: At the present time, most studies investigating gastrointestinal transit time with charcoal are conducted in fasted rats. It seems reasonable to hypothesize that the fasting state of rats could influence the effect a compound had on gastrointestinal transit time. The purpose of this study was to investigate the effects of food on the pharmacological effects on gastrointestinal transit. METHODS: For each drug investigated, two sets of 32 male Sprague-Dawley rats were used. One set was studied after being fasted for approximately 6 h, the second set was studied after free access to food. Each set had 4 groups of animals (n=8/group) that were administered different doses, allowing the assessment of the drug effect after fasting and after free access to food. Animals were administered 0, 10, 25, and 75 mg/kg of morphine; 0, 10, 20, and 40 mg/kg loperamide, or 0, 0.05, 0.5, and 3.0 mg/kg clonidine. At predetermined times, an activated charcoal suspension was administered by oral gavage. Thirty minutes after receiving the charcoal meal, rats were euthanized and the small intestine was removed. The length of the small intestine and the distance traveled by the charcoal were recorded. For each animal, gastrointestinal transit was calculated as the percentage of the distance traveled relative to the total length of the small intestine. RESULTS: Baseline (vehicle dosed animals) gastrointestinal transit was significantly greater in fasted versus fed rats. In fasted rats, morphine did not have a significant effect on transit. In fed rats, 25 and 75 mg/kg morphine caused a significant decrease in transit. In fed and fasted rats, 0.5 and 3 mg/kg clonidine caused a significant decrease in transit. Loperamide did not affect gastrointestinal transit in fed or fasted rats at doses up to 40 mg/kg. DISCUSSION: These data demonstrate that food does not reduce the sensitivity of the gastrointestinal transit time.

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Esta determinación se utiliza para describir aquellos episodios en los que un niño menor de un año,(en aparente estado de buena salud), sufre un cambio en su apariencia que es interpretado por los padres o adultos circundantes como un estado demuerte inminente. Definiremos al ALTE como aquel evento en que la madre o responsable del cuidado de un niño menor de 1 año refiere que éste presentó: 1- Un súbito cambio de color (palidáz, cianosis, rubicundez) 2- Hipotonía o menos frecuentemente hipertoníia 3- Alteraciones en la respiración 4- Luego de realizar alguna estimulación intensa (sacudida, respiración boca a boca) ligera o espontáneamente

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Since gastro-oesophageal reflux disease (GORD) is a prevalent condition characterised by frequent relapses, long-term costs of management for this disease are high. Thus, strategies to decrease resource expenditures without impairing patient quality of life are desirable. On-demand therapy (one-dose when symptoms occur) and intermittent therapy (short course of medication when symptoms occur) are attractive since pharmaceutical expenditures may be decreased, and many patients self-employ this strategy. The purpose of this paper was to examine the economic implications of on-demand or intermittent therapy for GORD. A review of selected studies evaluating medication suitable for on-demand or intermittent administration was performed. A complete search for published studies on the cost effectiveness of on-demand or intermittent therapy for GORD was conducted, and the results discussed in detail. Antacids, alginates, topically active agents, histamine(2)-receptor antagonists, and proton pump inhibitors have all demonstrable efficacy compared with placebo when administered on-demand. Proton pump inhibitors constitute the most effective pharmacological means to treat GORD. Although step-up strategies initially using less potent medication may decrease resource use, cost-effectiveness analysis illustrates that on-demand or intermittent therapy with proton pump inhibitors may be reasonable options. Further work that defines quality of life and patient preferences associated with GORD may allow for proper allocation of resources for the management of this condition.

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Gastroesophageal reflux disease (GERD), or the regurgitation of gastric content into the esophagus, is an acid-peptic disorder that has a significant impact on both health and the quality of life. Because gastric acid plays a major role in the pathophysiology of this disease, acid neutralization/suppression has emerged as the cornerstone of GERD therapy. Currently, there are 3 classes of drugs used to increase gastric pH: antacids, histamine2 receptor antagonists (H2RAs), and proton pump inhibitors (PPIs). Antacids act by neutralizing the pH of the stomach. However, because of their limited efficacy and short duration of action, they have not been shown to be effective in either the prevention or healing of GERD-induced esophageal injury. Moreover, numerous doses per day are often required to control GERD symptoms. A second class of agents, H2RAs, act by inhibiting a histamine-dependent biochemical pathway that stimulates acid secretion by the gastric parietal cell. However, because there are several other stimulatory pathways that also contribute to acid secretion, a lack of consistent efficacy of H2RAs exists among individuals. Moreover, because there are several pathways leading to acid secretion, patients who receive H2RAs often experience tachyphylactic reactions to these drugs. The PPIs are the latest and most effective medications for the treatment of GERD. Unlike H2RAs, PPIs block acid secretion at its source--the proton pump of the gastric parietal cell. Studies have consistently shown that PPIs are more effective than H2RAs in resolving GERD symptoms, healing erosive esophagitis, and preventing esophageal injuries. PPIs are also effective in the treatment of acid-peptic disorders other than GERD, such as duodenal and gastric ulcers. Four PPIs are currently available in the United States: omeprazole, lansoprazole, rabeprazole, and pantoprazole.

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