Erythromycin is the most potent drug when given intravenously (in doses of approximately 3 mg/kg or less) and may be particularly useful in the initial phase of management. When used orally, erythromycin may have greater efficacy when given as a suspension, rather than as a tablet, but is still probably less effective than when given intravenously. It is uncertain whether tachyphylaxis to the effects of erythromycin occurs as a result of downregulation of motilin receptors. It has recently been demonstrated, in healthy subjects and in patients with diabetes, that the response to erythromycin is markedly attenuated during hyperglycemia; it is uncertain whether this effect occurs with other prokinetic drugs. The drug of first choice for oral administration is probably cisapride, which appears to have the most diffuse gastrointestinal effects. While cisapride has been well tolerated in clinical trials, there have been recent reports of cardiac arrhythmias, including deaths. Read the rest of this entry »
Archive for the ‘Gastroparesis’ Category
Treatment of symptomatic gastroparesis is certainly not uniformly satisfactory, and novel therapeutic options are needed. Levosulpiride is a dopamine2 antagonist/5-HT4 agonist in development. There may be therapeutic advantages to combining drugs that have different mechanisms of action, such as cisapride and domperidone. (The combination of cisapride with erythromycin is usually contraindicated.) The recognition of the important role of sensory nerves in regulating local reflexes and signalling information to the central nervous system suggests that drugs designed to modulate sensory feedback from the gastrointestinal tract, such as 5-HT3 antagonists and kappa opiate agonists, may have a therapeutic role. Therapies designed to relax the proximal stomach and reduce gastric wall tension, such as sumatriptan and clonidine, may be useful when symptoms reflect an increase in the sensitivity of gastric mechanoreceptors or diminished gastric accommodation. Information relating to the effect of cholecystokinin A antagonists in patients with gastro-paresis is not yet available. Because erythromycin is associated with the risk of long term antibiotic use and, possibly, diminished efficacy, potent motilides that lack antibiotic activity have been developed. The therapeutic role of these compounds remains to be established. Novel 5-HT^ receptor agonists, which are not associated with potential cardiac toxicity, are also being evaluated. Cheapest medications online – actos buy for you to get healthy very soon.
It should be recognized that prokinetic drugs may also improve symptoms by effects unrelated to acceleration of gastric emptying. There is also renewed interest in the potential role of gastric electrical stimulation as a therapy, using either neural electrical stimulation at a high frequency (which probably stimulates vagal sensory nerves and may suppress the vomiting centre) or gastric electrical pacing, in which electrical stimulation of cholinergic motor neurons approximates the physiological frequency (approximately three cycles/min). While there are observations to suggest that both approaches may be beneficial, controlled trials are required.
Although other tests show promise, scintigraphy is the most accurate and arguably the only clinically useful assessment of gastric motility. Unfortunately, there is a lack of standardization of scintigraphic techniques, with substantial variation among different centres, particularly with respect to the choice of test meal and the calculation of gastric emptying rates. Therefore, each laboratory needs to have access to an appropriate control range. Gastroparesis is usually defined as an emptying rate that is more than two standard deviations outside such a range. In patients with gastroparesis, there is a relatively poor correlation between gastric emptying of solid and liquid meal components. Therefore, a dual isotope technique is preferable, although this adds to the complexity of the test. If it is only feasible for a single isotope to be used, emptying of solids is usually measured. There is little evidence that this approach offers any substantial advantage over the use of semisolid or nutrient-containing liquid meals, although it has been suggested that the use of solid markers that are of a firm texture and not readily fragmented may be optimal. You can find best quality treatment now – buy glucophage to see how cheap it is.
Scintigraphic breath tests have been used to quantify solid and liquid gastric emptying, most recently using stable isotopes. While these tests are substantially cheaper and simpler than external scintigraphy and avoid the use of irradiation, there is considerable debate regarding the appropriate method to analyze the data, and studies in patients with gastroparesis are limited. It seems likely that scintigraphic breath tests will prove to be useful as a screening test for gastroparesis and in large epidemiological studies.
The use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) is the mainstay of therapy, and most patients require drug treatment. In general, these drugs all provide dose-related improvements in gastric emptying, although their mechanisms of action differ (Table 2). The response to prokinetic therapy tends to be greater when gastric emptying is more delayed. Because comparisons among these drugs are limited, it is difficult to give confident therapeutic recommendations. With the possible exception of erythromycin, all of these drugs have been shown to improve symptoms and quality of life. There is some evidence that tolerance may develop to the gastrokinetic effects of metoclopramide and domperidone. The mechanical effects of prokinetic drugs that are responsible for faster gastric emptying are poorly defined; the dominant effect is likely related to a change in the organization of antroduodenal contractions to an expulsive pattern. The response to prokinetic therapy is variable, and there is evidence that patients with myopathic and neuropathic disorders due to defective extrinsic neural innervation may respond less favourably. Best quality drugs are waiting – buy levaquin 500 mg to spend less time and money.
The management of gastroparesis is often challenging. In any patient who presents with upper gastrointestinal symptoms and a suspected delay in gastric emptying, a comprehensive history and examination should be performed, followed by appropriate investigation to identify (particularly reversible) causes of gastroparesis. Upper gastrointestinal endoscopy is usually required to exclude gastric outlet or proximal small intestinal obstruction, as well as mucosal disorders. When results of these investigations are unremarkable, gastric emptying should ideally be measured by scintigraphy (and possibly, in the future, by scintigraphic breath tests), which enables treatment to be targeted. Because of uncertainties about the predictive value of symptoms, objective measurement is required for the diagnosis of gastroparesis, and nonspecific terms such as ‘gas-tropathy’ and ‘gastroparesis symptoms’ are probably best avoided. Despite these considerations, it is reasonable to give an empirical trial of prokinetic therapy for about four weeks, although it should be recognized that there is a substantial placebo response. However, there is no objective evidence to support the cost effectiveness of such an approach, and many patients require prolonged therapy. Gastric emptying must be measured if symptoms fail to improve or recur after the cessation of therapy and in patients who have had previous gastric surgery. While it is appropriate to initially attempt dietary modifications (eg, small meals, low fat, fibre solid foods and increased nutrient liquids), there is surprisingly little evidence to suggest that such an approach is useful. In patients with diabetes melli-tus, rigorous attempts should be made to optimize glycemic control.
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Alterations in glycemic control: Potential determinants of postprandial blood glucose concentrations include the delivery of nutrients to the small intestine, small intestinal absorption and hepatic glucose metabolism. While the relative contribution of each of these factors is controversial and likely to vary with time after a meal, it is clear that gastric emptying is a major determinant of the glycemic response to oral carbohydrate. In both normal subjects and patients with type 2 diabetes, the rate of gastric emptying accounts for approximately 35% of the variance in peak blood glucose after 50 to 75 g oral glucose loads. Moreover, carbohydrate-containing foods with high fibre or viscosity, and high fat meals that empty from the stomach slowly are associated with blunting of postprandial blood glucose concentrations. In patients with type 1 diabetes the postprandial insulin requirement is initially less when gastric emptying is slower; hence the insulin regimen for these patients should take into account the rate of gastric emptying. Delayed gastric emptying caused by irreversible autonomic nerve dysfunction or variations in the blood glucose concentration may contribute to poor gly-cemic control in patients with diabetes by causing a mismatch between the onset of action of the insulin or oral hypoglycemic drug, and the absorption of nutrients from the small intestine. However, evaluation of this concept poses substantial challenges. In contrast, there is ncreasing evidence that modulation of the rate of gastric emptying may be a useful therapeutic approach to improving glycemic control in patients with diabetes mellitus, thereby reducing the risk of micro- and macrovascular complications. The outcome of long term clinical trials is awaited, but it has been established that short term administration of pramlintide (a human amylin analogue) and glucagon-like peptide-1 reduces postprandial hyperglycemia in patients with uncomplicated type 1 diabetes by slowing gastric emptying. In patients with type 2 diabetes, slowing of gastric emptying, whether induced by dietary modifications, or administration of cholecystokinin, glucagon-like peptide 1, or pramlintide, also decreases postprandial glucose concentrations. There is only limited information about the chronic effects of prokinetic therapy on glycemic control in patients with type 1 diabetes. Pharmacological improvement of delayed gastric emptying may improve the coordination between insulin delivery and nutrient absorption. Buy cheap drugs online fast – cialis professional online for you to enjoy a reliable pharmacy.
Oral drug absorption: Gastric emptying is an important determinant of oral drug absorption; most orally administered drugs (including alcohol) are absorbed more slowly from the stomach than from the small intestine, because the latter has a much greater surface area. Thus, delayed gastric emptying (particularly that of tablets or capsules that are not degraded easily in the stomach) may lead to fluctuations in the serum concentrations of orally administered drugs; this is likely to be particularly relevant when a rapid onset of drug effect is desirable, as in the treatment of migraine and in diabetic patients taking oral hypoglycemic agents. There is relatively little information about drug absorption in patients with gastroparesis. However, changes in gastric emptying are not expected to have a major effect on steady-state blood concentrations of drugs that have longer half-lives, including prokinetic drugs. You can start online shopping right now – cialis professional for more advantages.