Gastric System

These observations of gastric ulceration may be related to the increased gastric acid secretion caused by capsaicin when administered into the stomach (Ketusinh a/., 1966 Solanke, 1973 Limlomwongse a/., 1979). In some reports, however, little or no effect of capsaicin or paprika on acid secretion (Lille and Ramirez, 1935 Toh etal., 1955 Sanchez-Palomera, 1951 Pimparkar et al., 1972) or on gastric ulcer healing time (Schneider et al., 1956) was found. These inconsistencies may be due to the different doses of capsaicin given and uncertainty in dose when only crude extracts of capsicum were employed. 

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In 1953, G. D. Searle and Co. patented a related compound, norethynodrel. This steroid is also an active contraceptive when taken orally. This fact is not at all surprising to an experienced organic chemist because it is well known that a CC double bond such as the one in norethynodrel is readily isomerized into conjugation with a carbonyl group. This acid-catalyzed isomerization occurs via an enol intermediate, and the equilibrium favors the more stable, conjugated compound. The acidic conditions in the human gastric system are quite sufficient to accomplish the transformation of norethynodrel to norethindrone. It seems that chemical reactions do not care much about patents ... 

Vitamin Bj deficiency can cause different pathological manifestations that affect the hematopoietic, neurological, and cardiovascular system, among others. One of the extreme forms of B,j deficiency, known as pernicious anemia, is not normally associated with diet but rather with problems in the gastric system caused by a lack of production of a gastric glycoprotein called intrinsic factor, which facilitates the absorption of the vitamin in the small intestine (Beck 2001). Due to the complexity of B hios5mthesis and to the limitations of the scope of this chapter, interested readers are invited to read excellent reviews that have been published on this subject (Roessner and Scott 2006 Escalante-Semerena 2007 Mera and Escalante-Semerena 2012). 

Mozzi, R, Gerbino, E., Font de Valdez, G., and Torino, M.l. (2009) Functionality of exopolysaccharides produced by lactic add bacteria in an in vitro gastric system. J Appl Microbiol 107, 56-64. 

Sodium bicarbonate is a gastric antacid that may cause systemic alkalosis on overdose and may contribute to edema owing to sodium retention. It is useful for systemic acidosis because both deficient ions are present in the same molecule, and it can be used topically as a moist paste or in solution as an antipmritic. Sodium bicarbonate also is an ingredient of many effervescent mixtures, alkaline solutions, etc. One gram of NaHCO neutralizes 115 mL 0.1 NHCl. 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

They also are important portals for systemic therapy. However, many variables can influence dmg dissolution and absorption ia these areas, including rate of gastric emptying, intestinal motility, mass and pH of intestinal contents, and condition of the absorbiag surfaces (15—17). These variables, ia turn, can be affected by the patient s disease, posture, and eating habits, and even by such aspects of the treatment as the timing of doses (11). 

Delivery systems that respond to changes in pH have been known to the pharmaceutical industry for more than a century. The pH-sensitive enteric coating is probably the oldest controUed-release technology. Unna introduced an enteric tablet coating based on keratin in 1884 (108). Enteric coatings are used primarily to protect the gastric mucosa from local irritation or to ensure that tablets do not dissolve until they reach the intestine. 

FIGURE 10.16 The H+,lO-ATPase of gastric mucosal cells mediates proton transport into the stomach. Potassimn ions are recycled by means of an associated K /Cl cotransport system. The action of these two pnmps results in net transport of and Cl into the stomach. 

The discovery of the antiulcer activity of H2 antihistamine antagonists has revolutionized the treatment of that disease. A benzimidazole. Omeprazole (55), inhibits gastric secretion and subsequent ulcer formation by a quite different mechanism. Studies at the molecular level suggest that this compound inhibits K /H dependent ATPase and consequently shuts down the proton pumping action of this enzyme system. 

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