Intestinal wall

Antibiotics (qv) have been fed at subtherapeutic levels to promote mminant animal growth. Possible reasons for the observed growth include decreased activity of microbes having a pathogenic effect on the animal, decreased production of microbial toxins, decreased microbial destmction of essential nutrients, increased vitamin synthesis or synthesis of other growth factors, and increased nutrient absorption because of a thinner intestinal wall... 

Niclosamide causes the tapeworm head to disengage from the intestinal wall of the host and the body wall of the parasite to disintegrate. The first... 

Quinacrine concentrates in the scolex of the parasite and causes the muscles needed for holding onto the intestinal wall to relax. The worms are stained yellow and pass from the body, still aUve. Quinacrine can intercalate with DNA and inhibit nucleic acid synthesis. It creates fluorescent bands in deoxyadenylate—deoxythmidylate-rich regions of DNA and has been used as a stain in the study of human genetics. 

Dmgs, such as opiates, may undergo metabolism both in the intestinal wall and in the fiver (first-pass metabolism). The metabolism may be extensive and considerably reduce the amount of dmg reaching the systemic circulation. Alternatively, the metabolite may be metabofically active and contribute significantly to the action of the parent dmg. Some compounds undergo enterohepatic circulation in which they are secreted into the GI tract in the bile and are subsequently reabsorbed. Enterohepatic circulation prolongs the half-life of a dmg. 

FIGURE 24.3 (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine, (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases. Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions. Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases. Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons (discussed in Chapter 25). 

The activity of pyrantel (Antimintii) is probably due to its ability to paralyze die helminth. Fbralysis causes die helminth to release its grip on die intestinal wall it is then excreted in die feces, pyrantel is used to treat round-worm and pinworm. Some patients receiving pyrantel may experience gastrointestinal side effects, such as nausea, vomiting, abdominal cramps, or diarrhea... 

Emollient laxatives lubricate the intestinal walls and soften the stool, thereby enhancing passage of fecal material. Mineral oil is an emollient laxative. 

Glycosides are the predominant forms. Although in humans flavonoids have been shown to be absorbed in their naturally occurring glycosidic forms (Hollman and Katan, 1998), isoflavones are not. It is generally accepted that to be adsorbed by enterocytes across the intestinal wall, isoflavone glycosides... 

Nowadays, consumers would like those antioxidants present in food products not only to stabilise food lipids, but also to be absorbed through the intestinal wall and protect the lipids of blood plasma against oxidation. This effect is relatively evident in the case of tocopherols (which are liposoluble) or ascorbic acid (which is hydrophilic), but much less evidence is available on antioxidants of medium polarity, such as flavonoids, rosemary oleoresins or green or black tea catechins. 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

Once absorbed, ezetimibe undergoes extensive glucuronida-tion in the intestinal wall to the active metabolite (ezetimibe glucuronide). Ezetimibe and the active metabolite are entero-hepatically recirculated back to the site of action, which limits systemic exposure and may explain the low incidence of adverse effects (Table 9-9). Ezetimibe alone or with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in LFTs. Currently, clinical trials designed to determine ezetimibe s effects on CHD morbidity and mortality have not been completed. The time until maximum effect on lipids for ezetemibe is generally 2 weeks. 

Kidney glomeruli, GI tract mucosa, exocrine and endocrine glands, certain tumors, pertibular capillaries, choroid plexus, pancreas, intestinal wall Sinusoidal... 

The absorption efficiency term allows estimation of the effective dose or the amount of pollutant which crosses the membrane of the exposed tissue (e.g., the lung) and reaches a target organ (e.g., the liver). For many pollutants this type of metabolic data is not available and consequently 100% absorption is a common preliminary assumption in exposure assessments. For well-studied substances such as radionuclides, a methodology for calculation of target organ doses has been developed for bone marrow, lungs, endosteal cells, stomach wall, lower intestine wall, thyroid, liver, kidney, testes and ovaries as well as for the total body. 

The plicae circulares, or circular folds, form internal rings around the circumference of the small intestine that are found along the length of the small intestine. They are formed from inward foldings of the mucosal and submucosal layers of the intestinal wall. The plicae circulares are particularly well developed in the duodenum and jejunum and increase the absorptive surface area of the mucosa about threefold. Each plica is covered with millions of smaller projections of mucosa referred to as villi. Two types of epithelial cells cover the villi ... 

The intestinal wall is optimized to absorb fluids and nutrients while keeping away different xenobiotics. Which factors, from a theoretical point of view, are the most influential in intestinal absorption ... 

Let us start by applying Fick s first law to the flux through the intestinal wall. At each point i on the intestinal surface the flux J is ... 

Table 18.2 lists 30 of the molecules used in this study that are known to be substrates for active transport or active efflux. The mechanistic ACAT model was modified to accommodate saturable uptake and saturable efflux using standard Michaelis-Menten equations. It was assumed that enzymes responsible for active uptake of drug molecules from the lumen and active efflux from the enterocytes to the lumen were homogeneously dispersed within each luminal compartment and each corresponding enterocyte compartment, respectively. Equation (5) is the overall mass balance for drug in the enterocyte compartment lining the intestinal wall. 

The absorption of class III drugs is limited by their permeability over the intestinal wall. Thus, as this process is not at all modeled by the classical in vitro dissolution test, no IVIVC should be expected. When drug dissolution becomes slower than gastric emptying, a reduction in the extent of bioavailability will be found in slower dissolution rates as the time when the drug is available for permeation over the gut wall in the small intestine will then be reduced. Thus, the same type of relationship can be expected between bioavailability and in vitro dissolution, as shown in Fig. 21.12 for a class I drug. 

The role of lipids on absorption has been extensively reviewed by Porter and Charman [29, 30]. The influences are diverse and include effects on luminal drug solubility, altering the metabolic and barrier function of the intestinal wall, stimulating lymphatic transport and a reduction in gastric transit, thereby increasing the time available for dissolution. 

HU, a freely water-soluble molecule, crosses the intestinal wall and other cells by passive diffusion [5, 6], and tissue concentration of HU rapidly matches its blood concentration [7]. The oral bioavailability of HU is nearly complete and hence therapeutically simple to administrate. HU undergoes biotransformation and is converted into urea by a yet-to-be identified hepatic P450 monooxygenase (CYP) enzyme [8, 9], Elimination of HU and its metabolites involves both renal and non-renal mechanisms. 

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