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PubMedDate not supplied

Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes.

There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given to any group of subjects. Such individual differences are largely due to variation in the rate of elimination of drugs. Gastrointestinal disease may also alter oral dose requirements by producing variation in both the amount and rate of drug absorption. These changes may be reflected in the plasma concentration/time curve that follows an oral dose. The amount of drug abosorbed is simultaneously affected by many factors. These include the physicochemical properties of the drug and the physiological factors that operate within the gut, as well as the presence of other substances such as food, or interaction with other drugs in the gut. The availability of the drug within the intestinal lumen is largely governed by its dissolution characteristics, particularly factors which can interfere with dissolution of the drug product in the gut. Physiological factors within the gut that affect oral drug absorption include gastric emptying rate and intestinal motility, the pH of the gastrointestinal fluids, the activity of gastrointestinal drug metabolising enzymes (e.g. monoamine oxidase and dopa decarboxylase) or drug metabolising bacteria and the surface area of the gut. Many factors affect gastric emptying. These include disease, surgery and other drugs. A change in the rate of gastric emptying alters the rate of drug delivery from the stomach to the duodenum and upper small intestine. This may profoundly alter the plasma concentration/time curve that follows oral administration of many drugs. For some drugs, proximal jejunal disease may reduce, delay or increase the apparent amount of drug absorbed. Reduced absorption of an antibiotic leads to a fall in the peak plasma concentration. If the peak falls below the minimum inhibitory concentration for a particular organism then therapeutic failure may occur, if it is assumed that the peak plasma concentration is all important for antimicrobial activity. Excessive drug absorption may lead to drug toxicity. Abnormal drug absorption is a feature of lower small intestinal conditions such as Crohn's disease. This suggests that drug absorption is not confined to the jejunum but continues throughout the small intestine. It is not always possible to predict the pattern of drug malabsorption from a knowledge of the physicochemical and pharmacokinetic properties of the drug and the pathophysiology of the disease. The rate and amount of drug absorbed be one patient may differ from that in another patient with the same condtion. Although these differences reflect normal individual variation, they are also related to the extent and activity of disease at the time of study...

Absorption↗
PubMed2004

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case-control study.

BACKGROUND: Clinical trials have suggested that cyclo-oxygenase-2-selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non-selective, non-aspirin, non-steroidal anti-inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding. AIM: To examine the risk of upper gastrointestinal bleeding in high-risk patients who filled prescriptions for cyclo-oxygenase-2 inhibitors or other non-steroidal anti-inflammatory drugs. METHODS: A population-based case-control study was performed in the Danish county of North Jutland from 1 January 2000 to 31 December 2002. From the County Hospital Discharge Registry and the Civil Registration System, we identified incident cases with upper gastrointestinal bleeding (n = 780) and randomly selected controls (n = 2906), respectively. All cases and controls had previous gastrointestinal diseases. Data on drug exposure were obtained from the countywide Prescription Database. RESULTS: Thirty-five cases (4.5%) filled prescriptions for cyclo-oxygenase-2 inhibitors within 30 days of the date of upper gastrointestinal bleeding, compared with 79 controls (2.7%). Adjusted odds ratios for upper gastrointestinal bleeding according to prescription for celecoxib, rofecoxib and non-steroidal anti-inflammatory drugs were 1.3 [95% confidence interval (CI), 0.7-2.8], 2.1 (95% CI, 1.2-3.5) and 3.3 (95% CI, 2.4-4.4), respectively. CONCLUSIONS: In patients with increased susceptibility to gastrointestinal adverse events, a lower risk of upper gastrointestinal bleeding was observed in users of cyclo-oxygenase-2 inhibitors compared with users of other non-aspirin, non-steroidal anti-inflammatory drugs.

Adolescent↗
PubMed1987

Circulating immunoreactive somatostatin in gastrointestinal diseases. Decrease after vagotomy and enhancement in active ulcerative colitis, irritable bowel syndrome, and duodenal ulcer.

The main source of circulating immunoreactive somatostatin (IRS) seems to be the gastrointestinal tract. We therefore investigated plasma IRS in patients with various gastrointestinal diseases. Mean basal IRS oscillated between 46 and 73 pg/ml. A postprandial rise was observed in all patients and age-matched controls. However, the increment was significantly higher in patients with duodenal ulcer (159 +/- 20 pg/ml), active ulcerative colitis (176 +/- 17 pg/ml), and irritable bowel syndrome (194.4 +/- 20.4 pg/ml). Patients with duodenal ulcers who underwent vagotomy showed a decreased postprandial increment (107 +/- 10 pg/ml) when compared with active duodenal ulcer patients. No difference was demonstrable between controls and individuals with gastric ulcer, and patients with inactive ulcerative colitis. These results suggest that vagal innervation plays a role in postprandial IRS stimulation, whereas gastric hyperacidity, acute lesions of the colonic mucosa, and hypermotility of the gastrointestinal tract are associated with an exaggerated postprandial IRS response. Since somatostatin is known to influence many gastrointestinal functions, these variations in circulating IRS concentrations may be of pathophysiologic importance.

Adult↗
PubMed2005

Proton pump inhibitors: update on their role in acid-related gastrointestinal diseases.

Gastric acid is pathogenic in many gastrointestinal disorders, such as gastroesophageal reflux disease and peptic ulcer disease. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for serious acid-related conditions. Ample recent data exist to explicate virtually every aspect of the clinical management of acid-peptic disorders with PPIs. Although all PPIs are effective, there are some differences in their clinical performance, particularly in terms of the degree and speed of gastric acid suppression. Rapid onset of acid suppression may be particularly relevant to newer approaches, such as 'on-demand' or intermittent therapy for non-erosive reflux disease and shorter regimens for Helicobacter pylori eradication. New data, in addition, highlight differences in PPI metabolism that may both affect efficacy and predispose patients to drug-drug interactions. PPI selection should involve the awareness of these issues.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Upper gastrointestinal diseases in the elderly: report of a meeting held at Vicenza, Italy, on 20 March 1998.

The aim of this article is to summarize the recent progress in geriatric/gastroenterological topics, particularly of the upper gastrointestinal tract, which were the focus of the First International Meeting on Upper Gastrointestinal Diseases in the Elderly, held in Vicenza, Italy, in March 1998. The Meeting was divided into three sections: gastro-oesophageal reflux disease (GORD) in the elderly, Helicobacter pylori infection in the elderly, and nonsteroidal anti-inflammatory drugs (NSAIDs) and the upper gastrointestinal tract in the elderly. GORD presents unique clinical features in elderly patients. The changes in oesophageal function, particularly disorders of motility, only partially explain its unique clinical manifestation. The diagnostic, clinical and therapeutic characteristics of GORD in the elderly need to be studied with attention to avoid its severe local complications, i.e. bleeding, stenosis and Barrett's oesophagus, as well as the more generalized risks of disability, impairment of nutritional status and reduction in the quality of life. Epidemiological studies have demonstrated that the prevalence of H. pylori infection increases with ageing and that subjects living in nursing homes have discrete epidemiological characteristics which render them a high-risk group. The incidence of some histological modifications of the gastric mucosa, particularly intestinal metaplasia, gastric atrophy and gastric cancer, seems to be both age- and H. pylori-related; their study in elderly subjects could give the key to understanding the pathophysiological mechanisms of H. pylori gastric damage. NSAID-related gastroduodenal damage, particularly haemorrhage, increases with age. Ageing, per se, does not modify significantly gastric aggressive factors, such as acid and pepsin secretions; however, a selective and specific reduction in some gastric defensive mechanisms seems to occur with ageing. Clinical studies on prevention of NSAID damage have rarely been performed in an elderly population, and meta-analyses of published data can lead to conflicting conclusions from a pharmaco-economic perspective. The identification of risk factors of NSAID-related gastroduodenal damage must be the foundation of preventive medical care for elderly subjects.

Aged↗
PubMed1950

Gastrointestinal allergic disease.

Gastrointestinal allergic disease undoubtedly does exist, but its frequency has been tremendously overrated. It is believed that in many cases there is not sufficient evidence for attributing chronic, recurrent digestive disturbances to allergic reaction, and that skepticism is particularly important because such a diagnosis exposes the patient to an unwarranted type of dietary management that is complicated, frequently unwise, and not too infrequently used as a substitute for critical clinical thinking. The demonstration and subsequent elimination of allergic substances that may at times be productive of digestive symptoms is, of course, important, and when based on proper evaluation of a carefully taken history will undoubtedly yield brilliant results.

Anaphylaxis↗