Gastrointestinal tract, upper

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

A pH-sensitive gel, poly(AAc), was used as a coating on capsules containing insulin and surfactant. The capsules protected against insulin release in the upper gastrointestinal tract. As the pH increased to 7.5, drug release increased... 

In a recent publication, investigators used a specially customized ISO-NOP sensor to monitor, in real time, NO production in the stomach and esophagus of human patients [82], In this method a patient first swallowed two NO electrodes (see Fig. 1.6), which were then withdrawn slowly at 1cm increments every 2 min. The investigators were then able to establish a profile of NO concentration in the upper gastrointestinal tract. 

Hill M Normal and pathological microbial flora of the upper gastrointestinal tract. Scand J Gastroenterol Suppl 1985 111 1-6. 

Boseman T, Anuras S, Hutton E, Ghandour E, Mikeska C Abnormal motility of the upper gastrointestinal tract in Parkinson s disease. Am J Gastroenterol 1990 85 1264A. 

In the periphery, 5-HT4 receptor mRNA is found in vascular smooth muscle. Newly developed drugs that activate 5-HT4 receptors are of interest for their potential in treating cardiac arrhythmia. The 5-HT4 receptor is also located on neurons of the alimentary tract, for example the myenteric plexus of the ileum, and on smooth muscle cells and secretory cells of the gastrointestinal tract, where they evoke secretions and the peristaltic reflex. 5-HT4 receptor agonists (e.g. cisapride, prucalopride, tegaserod) are used therapeutically in the treatment of constipation-predominant irritable bowel syndrome and in functional motility disorders of the upper gastrointestinal tract. 

A second example is the colon-specific delivery of glucocorticoids linked to dextran via a succinic acid or glutaric acid spacer [256a]. Such conjugates resist hydrolysis in the upper gastrointestinal tract, but are rapidly degraded by bacteria in the colon and caecum where little drug absorption occurs. 

Allen, A., Bell, A., and MacQueen, S. (1984). Mucus and mucosal protection. In "Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract" (A. Allen, G. Flemstrom, A. Garner, W. Silen, and L. A. Turnberg, eds), pp. 195-201. Raven Press, New York. 

Certain substances may need special consideration, such as highly electrophilic substances, which give positive results in vitro, particularly in the absence of metabolic activation. Although these substances may react with proteins and water in vivo and thus be rendered inactive toward many tissues, they may be able to express their mutagenic potential at the first site of contact with the body. Consequently, the use of test methods that can be applied to the respiratory tract, upper gastrointestinal tract, and skin may be appropriate. 

A study of 204 workers exposed for from 1 month to 20 years to 2,4,5-T and its contaminants (concentrations unspecified) showed no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, central or peripheral nervous system effects, reproductive problems, or birth defects. Clinical evidence of chloracne persisted in 55.7%, and an association between exposure and history of upper gastrointestinal tract ulcer was found. 

Engfer, M. B., Stahl, B., Finke, B., Sawatzki, G., and Daniel, H. (2000). Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am. ]. Clin. Nutr. 71,1589-1596. 

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

Acute fresh bleeding from the upper gastrointestinal tract is a mandatory cause of hospital referral. About half of all cases are due to peptic ulceration, and variceal bleeding accounts for a varying, but generally minor component of the remainder depending on the frequency of alcoholic cirrhosis or of hepatitis B-induced cirrhosis in the population. 

Adverse reactions associated with probenecid therapy include occasional rashes, allergic dermatitis, upper gastrointestinal tract irritation, and drowsiness. The drug is contraindicated in patients with a history of renal calculi. 

These antibiotics are partially absorbed from the stomach and upper gastrointestinal tract. Food impairs absorption of all tetracyclines except doxycycline and minocycline. Absorption of doxycycline and minocy-cbne is improved with food. Since the tetracyclines form insoluble chelates with calcium (such as are found in many antacids), magnesium, and other metal ions, their simultaneous administration with milk (calcium), magnesium hydroxide, aluminum hydroxide, or iron will interfere with absorption. Because some of the tetracyclines are not completely absorbed, any drug remaining in the intestine may inhibit sensitive intestinal microorganisms and alter the normal intestinal flora. 

NT099 Nair, U. ]., N. Ammigan, J. J. Kayal, and S. V. Bhide. Species differences in hepatic pulmonary and upper gastrointestinal tract biotransformation enzymes on long-term feeding of masheri—a pyrolyzed tobacco product. 

OS 150 Hildebrandt, L. A., and J. A. Marlett. Starch bioavailability in the upper gastrointestinal tract of colectomized rats. JNutr 1991 121(7) 1141. 

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