Gastric acid secretion blocking

Fellenius E, Berglindh T, Sachs Getal(1981) Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature 290 159-161... 

The proton pump inhibitors suppress gastric acid secretion by blocking the final step in the production of gastric acid by the gastric mucosa... 

PPIs block gastric acid secretion by inhibiting hydrogen potassium adenosine triphosphatase in gastric parietal cells, which results in profound and long-lasting antisecretory effects. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Nonselective antimuscarinic drugs have been employed in the therapy of peptic ulcers (see Chapter 40) because they can reduce gastric acid secretion they also have been used as adjunctive therapy in the treatment of irritable bowel syndrome. Antimuscarinic drugs can decrease the pain associated with postprandial spasm of intestinal smooth muscle by blocking contractile responses to ACh. Some of the agents used for this disorder have only antimuscarinic activity (e.g., propantheline), while other drugs have additional properties that contribute to their antispasmodic action. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic concentrations primarily have a direct smooth muscle relaxant effect with little antimuscarinic action. 

A 55-year-old man who works in the furnace room at a steel foundry has developed chronic peptic ulcer disease that has not responded to treatment with antibiotics and H2 receptor blockers. You are considering giving him an antimuscarinic drug to block gastric acid secretion as adjunctive therapy. What are your concerns regarding the suitability of this treatment for this worker ... 

Answer Antimuscarinics are not frequently used for peptic ulcer disease today because of their many side effects, but they stiU can play a useful role as adjunctive therapy. Unfortunately, high concentrations are required to block gastric acid secretion, which means that many side effects are difficult to avoid. This man works in a dangerous environment, and his concentration cannot be compromised. Although CNS depression and loss of concentration is a concern with tertiary amine muscarinic antagonists, quaternary ammonium muscarinic antagonists... 

Stimulation of gastric acid secretion is the most important response it is blocked only by Hj antagonists. As mentioned before, the hormone gastrin may be involved in histamine release, because Hj antagonists block gastrin-induced acid secretion. 

H2 receptors are involved primarily in the regulation of gastric acid secretion. Drugs that selectively block the H2 receptor (referred to simply as H2 antagonists) may help control gastric secretion in conditions such as peptic ulcer these drugs are discussed in Chapter 27. 

Hi receptor antagonists block the actions of histamine by reversible competitive antagonism at the Hi receptor. They have negligible potency at the H2 receptor and little at the H3 receptor. For example, histamine-induced contraction of bronchiolar or gastrointestinal smooth muscle can be completely blocked by these agents, but the effects on gastric acid secretion and the heart are unmodified. 

Proton pump inhibitors, like H2-receptor antagonists, act at parietal cells and decrease gastric acid secretion. Proton pump inhibitors specifically block proton pumps,... 

D. Blocking receptor activation of gastric acid secretion... 

Increased gastric acid secretion may increase the risk of ulcers Bradycardia or heart block may occur in patients with or without cardiac impairment... 

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