- Each factor attributes to a common final physiological event—the secretion of H + by parietal cells, which are located in the body and fundus of the. - Their respective specific receptors (M 3 , H 2 , CCK 2 receptors) have been anatomically and/or pharmacologically localized to the basolateral membrane of the parietal cell. - of gastric acid secretion are the dorsal motor nucleus of the vagal nerve (DMNV), the. - Efferent fibers originating in the DMNV descend to the stomach via the vagus nerve and synapse with ganglion cells of the enteric nervous system (ENS). - Gastrin primarily is present in the antral G cells. - Structures of four inhibitors of the gastric H + ,K + –ATPase (proton pump). - Conversion of omeprazole to a sulfenamide in the acidic canaliculi of the parietal cell. - The sulfenamides interact covalently with sulfhydryl groups in the extracellular domain of the proton pump, thereby inhibiting its activity.. - The granules dissolve only at an alkaline pH, thus preventing degradation of the drugs by acid in the esophagus and stomach. - Proton pump inhibitors also are the mainstay in the treatment of Zollinger-Ellison syndrome. - Small amounts (from <10% to 35%) of these drugs undergo metabolism in the liver. - Hemodialysis and peritoneal dialysis clear only very small amounts of the drugs. - administration of the drugs. - absorption and subsequent bioavailability of the H 2 -receptor antagonists (see"Antacids,". - (deesterification) to form misoprostol acid (the free acid), the principal and active metabolite of the drug. - The elimination half-life of the free acid, which is excreted mainly in the urine, is about 20 to 40 minutes.. - Sucralfate ( CARAFATE ) consists of the octasulfate of sucrose to which aluminum hydroxide has been added. - physiological effects of the cation, by water solubility, and by the presence or absence of food in the stomach (seeTable 37–3 for a comparison of some commonly used antacid preparations). - Alkalinization of the gastric contents increases gastric motility, through the action of gastrin. - They are classically thought to be antagonists of the M 1 cholinergic receptor and may act to suppress neural stimulation of acid production (the receptor on the parietal cell itself is of the M 3 subtype). - Antagonists of the gastrin receptor on parietal cells (CCK 2 receptor) currently are under study.. - Because of the wide clinical spectrum associated with GERD, the therapeutic approach is best tailored to the level of severity in the individual patient (Figure 37–6). - counterproductive because of the higher costs associated with ineffective therapy.. - pylori infection of the stomach. - pylori also is indicated in the treatment of MALT-lymphoma of the stomach, as this can regress significantly after such treatment.. - This is felt to be a consequence of the improvement in H. - Stress ulcers are ulcers of the stomach or duodenum that usually occur in the context of a major systemic or CNS illness or trauma (ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis, 1999). - This can be achieved by any of the acid production–suppressing agents as well as antacids (Cook et al. - This can lead to severe gastroduodenal ulceration and other consequences of the uncontrolled hyperchlorhydria. - Impressive advances have been made in the pharmacological treatment of acid-peptic disorders.. - These have been made possible largely by the availability of the proton pump inhibitors and the discovery of H. - Other advances should result from a greater understanding of the pathophysiology of GERD. - investigation of the patient, giving rise to the term "functional bowel disorders,". - Autonomous motor activity of the gut, best illustrated in the intestine, displays two broad patterns.. - collection of nerves within the wall of the gastrointestinal tract. - The net pressure gradient creates forward movement of the bolus. - The Neuronal Network Responsible for Initiation and Generation of the Peristaltic Reflex. - enterochromaffin cells (8), which excites the intrinsic primary afferent neuron (1), which then communicates with both ascending (2) and descending (3) interneurons in the local reflex pathways. - In turn the activity of the modulatory neurons can be affected by various. - Modifications of the structure of acetylcholine have led to. - Serotonin (5-HT) is an extremely important substance in the gastrointestinal tract and is present in both enterochromaffin cells of the mucosa and neurons of the myenteric plexus. - Clinically, one of the greatest needs for prokinetic agents is in patients with delayed gastric emptying. - Cisapride is no longer generally available in the United States. - Metoclopramide is one of the oldest true prokinetic agents. - Tegaserod ( ZELMAC ) may be approved by the United States Food and Drug Administration (FDA) in the near future.. - Motilin is a 22–amino acid peptide hormone found in the gastrointestinal M cells as well as in some enterochromaffin cells of the upper small bowel. - relaxations (tLESRs) are prolonged relaxations of the LES that occur in the absence of a swallow and appear to be the dominant factor in reflux in most patients. - Anatomical factors such as hiatal hernia also can contribute to the impaired integrity of the antireflux barrier.. - The process appears to be coordinated by a central emesis center in the lateral reticular formation of the mid-brainstem adjacent to the CTZ in the area postrema (AP) at the bottom of the fourth ventricle and the nucleus tractus solitarius (NTS) of the vagus nerve. - Vomiting in response to stimulation of the emetic center is a complex response and is described in the text.. - since its introduction in the early 1990s, it and other 5-HT 3 -receptor antagonists have become some of the most widely used drugs for chemotherapy-induced emesis (Gregory and Ettinger, 1998. - The chemical structures of the three agents currently available in the United States are shown below.. - Both active and inactive metabolites are formed in the liver, the principal example of the former being 11-OH-delta-9-tetrahydrocannabinol. - Inhibitors of the Synthesis and Actions of Adrenocortical Hormones.. - Antagonists of the NK1 subtype of substance P receptors have been shown to have antiemetic effects (Rupniak and Kramer, 1999). - Recently, a synthetic, nonpeptide antagonist of the NK1 receptor was found to be effective as a single agent in the prevention of delayed nausea after cisplatin therapy (Navari et al. - The discovery of the 5-HT 3 –receptor antagonists has led to a major advance in the treatment of nausea and vomiting, especially in the postchemotherapy setting. - By contrast, treatment of the. - Net absorption of the water occurs in the small intestine in response to osmotic gradients that result from the uptake and. - The absorptive capacity of the colon is 4 to 5 liters per day. - their principal utility is in the provision of. - It is useful in the treatment of bile salt–induced diarrhea, as in patients with resection of the distal ileum. - In these patients, there is partial interruption of the normal. - In the low pH of the stomach, the bismuth subsalicylate reacts with hydrochloric acid to form bismuth oxychloride and salicylic acid. - The latter is absorbed in the stomach and small intestine, leaving 99% of the bismuth to pass unaltered and unabsorbed into the feces.. - A recommended dose of the liquid bismuth subsalicylate. - Likewise, a darkening of the tongue occurs because of a reaction between the drug and sulfides produced by bacteria in the mouth. - The most common antibacterial use of this agent is in the treatment of Helicobacter pylori (see Chapter 37: Agents Used for Control of Gastric Acidity and Treatment of Peptic Ulcers and Gastroesophageal Reflux Disease).. - In patients with active inflammatory disease of the colon, loperamide should be used with great caution, if at all, to prevent development of toxic megacolon.. - Because of the short half-life of somatostatin, it can be given only by intravenous infusion (250 g bolus dose followed by 250 g hourly). - There is evidence that some patients with constipation have increased SSBs correlated with prolongation of the intestinal transit time. - of the mass action type as well as "increased motility". - of the nonpropulsive type may lead to constipation. - calcium in the stool and osteomalacia of the vertebral column.. - Laxatives generally have been thought to act in one of the following ways: (1) retention of. - A few patients dislike the sweet taste of the preparations. - of the ammonia by its conversion to the polar ammonium ion. - Bisacodyl is mainly excreted in the stool. - This process is reversed by bacterial action in the colon with the formation of the active forms. - A melanotic pigmentation of the colonic mucosa (melanosis coli) has been observed in the colon in patients using anthraquinone laxatives for long periods (at least 4 to 9 months). - The source of the pigment is not clear. - histology reveals loss of myenteric plexus neurons and atrophy of the muscularis propria. - Currently available prokinetic agents are not very useful in the treatment of constipation. - however, is responsible for most of the significant adverse effects of the preparation.. - Regardless of the severity, once remission has been achieved, the drug plays a useful role in the prevention of relapses.. - the rest (about 10%) is excreted unchanged in the urine. - increments of the dose. - The fact that most of the side effects of sulfalsalazine are related to the relatively inactive. - sulfapyridine component spurred the development of the newer 5-ASA preparations. - To achieve this goal without the use of the sulfonamide moiety, several innovative approaches have been developed (Table 39–8). - Inhibitors of the Synthesis and Actions of Adrenocortical Hormones). - Inhibitors of the Synthesis and Actions of Adrenocortical Hormones),. - enzyme thiopurine methyltransferase (TPMT), which varies with the genetic makeup of the patient.. - synthesized from cholesterol in the liver. - The secondary acids are absorbed in the. - of the total bile acid pool). - it is formed by epimerization of the primary bile acid chenodeoxycholic acid (CDCA. - chenodiol) in the gut by intestinal bacteria. - this represents about 10% of the normal pancreatic output. - Until we have a better understanding of the
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