Gastric acid production

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

Mechanism of Action Aproton pump inhibitor that is converted to active metabolites that irreversibly bind to and inhibit hydrogen-potassium adenosine triphosphates, an enzyme on the surface of gastricparietal cells. Inhibits hydrogen ion transport into gastric lumen. Therapeutic Effect Increases gastricpH, reducing gastric acid production. 

Iron absorption occurs predominantly in the duodenum and upper jejunum. The physical state of iron entering the duodenum greatly influences its absorption. At physiological pH, ferrous iron is rapidly oxidized to the insoluble ferric form. Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron. When gastric acid production is impaired, iron absorption is reduced substantially. Ascorbic acid enhances iron absorption. Ascorbic acid mobilizes iron from iron-binding proteins in vivo, which in turn could catalyze lipid peroxidation. Iron absorption is inhibited by antacids, phytates, phosphates and tetracyclines. 

There is a diversity of histamine receptors. The H2, H3 and H4 receptors are of interest in gastrointestinal pharmacology. Histamine H2 receptors are G protein-coupled receptors which act by increasing intracellular cAMP to stimulate gastric acid production, and blockade reduces acid secretion. 

Omeprazole is a racemate, from which the R- and S-isomers are isolated as reported by Kendall [155]. Both of these isomers convert to the same inhibitor of the H+/K+-ATPase and produce the same reduction in the gastric acid secretion. The S-isomer, esomeprazole, is metabolized more slowly and reproducibly than the R-isomer of omeprazole and therefore produces higher plasma concentrations for longer and, as a result, inhibits gastric acid production more effectively and for longer. Esomeprazole has the pharmacological properties of a more effective form of treatment for disorders related to gastric acid secretion. 

Lindberg et al. [169] proposed a mechanism of action for omeprazole, the inhibitor of the gastric H+/K+-ATPase, which is responsible for the gastric acid production and located in the secretory membranes of the parietal cell. Omeprazole itself is not an active inhibitor of this enzyme,... 

Gastric pH is higher in newborns (pH 6-8) than in adults (pH 1-3), thus causing differences in ionization and absorption of certain chemicals (Radde, 1985). Adult levels of gastric acid production are reached at about two years of age. The alkaline gastric pH in newborns and infants may lead to enhanced bioavailability of weakly basic compounds but reduced bioavailability of weakly acidic compounds (Alcorn McNamara, 2003). 

Diminishes gastric acid production by inhibiting adenylyl cyclase... 

Calcium carbonate preparations for many years have been used by humans in large amounts on a self-prescription basis or as recommended by physicians in control or treatment of upper gastrointestinal distress conditions which are thought to be related to gastric acid production. These include dyspepsia, peptic ulcers,... 

Eor further information, see Focus on Controlling Gastric Acid Production. 

Gastric acid production is regulated by both the autonomic nervous system and several hormones. The parasympathetic nervous system, via the vagus nerve and the hormone gastrin, stimulates the parietal cell to produce gastric acid, acting both directly on parietal cells and indirectly through the stimulation of the secretion of the hormone histamine from ECL cells. Vasoactive intestinal peptides, cholecystokinin and secretin all inhibit acid production. 

Gastrointestinal PGE2 normally acts to inhibit gastric acid production, and also stimulates secretion of mucous. Reduction in PGE2 (by aspirin) may lead to ulceration and gastric distress. 

There are at least two different types of COX, COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 (which is constitntive) this leads to an inhibition of prostanoid synthesis, and reduced levels of PGE2 in particular lead to an increase in gastric acid production (Chapter 4), as weU as a reduction in mucous secretion. Aspirin also modifies the enzymatic activity of COX-2 (which is inducible) normally COX-2 produces prostanoids, most of which are pro-inflammatory, but aspirin-modified COX-2 produces lipoxins, which are anti-inflammatory. 

FUNCTION Promote gluconeogenesis and protein and fat breakdown antiinflammatory increase gastric acid production. 

Vhe four steps that occur during gastric acid production are outlined in Figure 22fi. T he goal is the secretion of HCI, a strong acid. Step 1 shows the membrane-bound protein that facilitates the release of protons from the cell. Transport of protons from the cell is potentially difficult, b ause their concentration FI the cell is very low (about 10" M). The secreted fluid has a proton concentration that is about one million times higher, 10" M (i.e., pH 1.0). 

The mechanism presented for gastric acid production did not reveal the source of protons and chloride ions. Continued production of gastric acid by this mechanism would result in depletion of the chloride ions in the cell and alkalinization of the cell because of the loss of protons. Figure 2.27 shows that the source of chloride ions is the bloodstream and the source of protons is carbonic add, H COj. As detailed in a later section, carbonic acid is produced by the action of carbonic anhydrase, the enzyme that catalyzes the reversible condensation of a molecule of water with a molecule of carbon dioxide. Carbonic acid ionizes to produce a... 

As discussed earlier, carbonic acid is a source of protons in gastric acid (HCl) production. The bicarbonate anion, which might be considered a byproduct of gastric acid production, is transported out of the parietal cell into the bloodstream. 

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