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About Gastric Ulcer



Histamine H2 Receptor Antagonists


        Their main action of anticholinergic drugs is to inhibits acetylcholine secreted by postganglionic cholinergic nerves. They also have an action on smooth muscle, which does not have cholinergic innervation. The more precise term for agents with both these action is 'antimuscarinic'. Atropine has been available for many years. It is well absorbed from gut. It has widespread anticholinergic actions apart from its effect on gastrointestinal tract. As a result, there are frequent side-effect. These include a decrease in salivary and bronchial secretion, dilatation of the pupil and an increase in heart rate. In very large doses, atropine also inhibits micturition and intestinal motility. The frequent side-effects of the earlier anticholinergics were the incentive to find more specific members of the group. This led to the development of agents such as propantheline, poldine and methlyscopolamine. These tend to be poorly absorbed. Absorption of methylscopolamine after oral dosage is only between 15% and 25%.

        Recent developments suggest that there are two types of muscarinic receptors, M1 and M2. It is probable that the older agents such as atropine inhibit both types of receptor whereas the more refined agent pirenzipine inhibits M1 responses at doses far below those required to block M2-mediated effects. Pirenzipine has been shown to inhibit gastrin responses in research methods designed to reproduce physiological vagal stimulation of gastric acid secretion. This may represent its main mode of action. Only a few of the many anticholinergic drugs have been shown conclusively to reduce acid secretion after oral administration in standard doses. Response to these agents show wide individual variation even in patients on the same dose of a drug. In one study, the mean inhibition of three hour food stimulated acid secretion was 32% after administration of poldine. However, the individual response of five subjects varied from 0 to 60% inhibition. (2)

       The frequency and types of side-effects with the older anticholinergic drugs have been discussed above. Though the newer agent, pirenzipine, seems to be more acceptable it does share some of the side-effects, particularly in the high doses in which is now most commonly used. Texter and Riley (1982) reported frequent side-effects with this drug in its 150mg daily dosage. Dry mouth was reported in 13.5% of patients, 6.3% had visual disturbance and constipation occurred in 2.6%.

        Antimuscarinics (except dicyclomine, ipratropium, oxybutynin, and tolterodine) are used as adjunctive therapy for peptic ulcer disease. However, there are no conclusive data from well-controlled studies which indicate that, in usually recommended dosages, antimuscarinics aid in the healing, decrease the rate of recurrencem or prevent complications of peptic ulcers. The efficacy of antimuscarinics for the treatment of gastric ulcers has also been questioned by many clinicians, In patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis.

        Antimuscarinics have been administered before meals to prolong and potentiate the effects of postprandial antacid therapy. However, controlled studies have failed to demonstrate a substantial difference in gastric pH when combined antimuscarinic and antacid therapy was compared to antacid therapy alone. Some clinicians use as antimuscarinic in conjunction with a histamine H2-receptor antagonist to potentiate the inhibitory effects on food-stimulated gastric acid secretion. A regimen that included antacids, an antimuscarinic and a histamine H2-receptor antagonist has also been used effectively to reduce gastric acidity. (3)


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