Gut mucosa

Pro-drugs (e.g. earbenicillin esters, ampicillin esters Fig. 5.2, Table 5.1) are hydrolysed by enzyme aetion after absorption from the gut mucosa to produce high blood levels of the aetive antibiotic, earbenicillin and ampicillin, respectively. 

It has the ability to cross the placenta and therefore provides a major line of defence against infection for the newborn. This can be reinforced by transfer ofcolostral IgG across the gut mucosa of the neonate. It diffuses readily into the extravascular spaces where it can act in the neutralization of bacterial toxins and can bind to microorganisms enhancing the process of phagocytosis (opsonization). This is due to the presence on the phagocytic cell surface of a receptor for Fc. 

Danaparoid sodium Prepared from animal gut mucosa contains heparin sulfate (84%), dermatan sulfate (12%), and chondroitin sulfate (4%)... 

Translocation Movement of bacteria and endotoxin from the intestinal lumen through the gut mucosa and into the lymphatic and systemic circulation. 

An idealised eukaryotic epithelium is represented in Figure 1. This might, for example, be the gut mucosa, the reabsorbing portion of a renal tubule system, or a gill epithelium. The solute must move from the bulk solution (e.g. the external environment, or a body fluid such as urine) into an unstirred layer... 

Intestinal Metabolism Intestinal drug metabolism can occur by microflora present in the gut lumen, as well as by enzymes present in luminal fluids and in the intestinal mucosa [166], Metabolism of xenobiotics by gut microflora is low in comparison to metabolism by the gut mucosa and liver [62], However, the intestinal microflora (e.g., Bacteroides and Bifidobacteria) may play an important role in the first-pass metabolism of compounds that are poorly or incompletely absorbed by the gut mucosa, especially in the lower parts of the intestine. This bacterial metabolism is largely degradative,... 

The phenotype of tolerance may or may not be dependent on the route of administration. For instance, it makes sense that oral delivery of antigen might provoke a TGF-(3-producing Th3 population, or a Foxp3+ population, given that the gut mucosa and the associated lymphoid tissues are rich in the TGF-[3 needed to drive such a response [12]. In contrast, the long-held belief... 

Chlorpromazine was the first, and probably is still the most widely used, major tranquilizer. Although 95-98 of the drug in plasma is bound to protein, it is extensively and rapidly metabolized within the body into a large number of metabolites. Much of the metabolism may indeed take place in the gut before, or in the gut mucosa during absorption. 

The vagus nerve is a major connection between central and peripheral components. It contains both afferent (80%) and efferent (20%) pathways from and to the upper GIT. These include both cholinergic and non-cholinergic nerve fibres the non-cholinergic neurones may have serotonin as transmitter. Two types of vagal afferent receptors are involved in the emetic response (1) mechanoreceptors, iocated in the muscular wall of the distal stomach and proximal duodenum, which are activated by distension or contraction of the gut wall and (2) chemoreceptors located in the gut mucosa of the upper small bowel. These monitor the... 

Grdic D, Homquist E, Kjerrulf M, Lycke NY Lack of local suppression in orally tolerant CD8-deficient mice reveals a critical regulatory role of CD8+ T cells in the normal gut mucosa.. 1 Immunol 1998 160 754-762. 

Fluorouracil is normally given intravenously (Table 55-3) and has a short metabolic half-life on the order of 15 minutes. It is not administered by the oral route because its bioavailability is erratic due to the high levels of the breakdown enzyme dihydropyrimidine dehydrogenase present in the gut mucosa. Floxuridine (5-fluoro-2 -deoxyuridine, FUDR) has an action similar to that of fluorouracil, and it is only used for hepatic artery infusions. A cream incorporating fluorouracil is used topically for treating basal cell cancers of the skin. 

Humans have a high concentration of xenobiotic-metabolizing enzymes in the gut mucosa and in the liver. This arrangement ensures that systemic exposure to potentially toxic chemicals is limited. A high percentage of these may be caught in first-pass metabolism. However, the normally beneficial first-pass metabolism... 

Role of the Gut Mucosa in Metabolically Based Drug-Drug Interactions... 

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