Inhibition And Neutralisation Of Gastric Acid

Healing of gastric and duodenal ulcers by antisecretory drugs and antacids is dependent upon:

• the degree of gastric acid suppression and

• the duration of treatment.

Proton pump inhibitors, which are the most potent antisecretory drugs, heal the majority of peptic ulcers within 4 weeks whereas the less powerful H2-receptor antagonists require up to twice as long to achieve the same healing rate. Antacids modify intragastric pH only transiently, yet relatively small daily doses (around 120 mmol) will heal ulcers if they are taken for long enough. By the end of three months 85% of peptic ulcers will have healed, regardless of the treatment, but the stronger agents provide much more rapid symptom relief. In addition, numerous studies have shown a high rate of placebo response in ulcer healing.

Antacids are basic substances that reduce gastric acidity by neutralising HC1. The hydroxide is the most common base but trisilicate, carbonate and bicarbonate are also used. Therapeutic efficacy and adverse effects depend also on the metallic ion with which the base is combined, and this is usually aluminium, magnesium or sodium. Calcium and bismuth have largely been abandoned for this purpose because of systemic toxicity. Preparations containing calcium may cause rebound acid hypersecretion and, with prolonged use hypercalcaemia and alkalosis. This may rarely be associated with renal failure (the 'milk-alkali syndrome'). Some bismuth preparations may be absorbed, causing encephalopathy and arthropathy; this is not a problem with bismuth chelate (see below).

Antacids protect the gastric mucosa against acid (by neutralisation) and pepsin (which is inactive above pH 5, and which in addition is inactivated by aluminium and magnesium). Continuous elevation of pH by intermittent administration is limited by gastric emptying. If the gastric contents are liquid, half will have left in about 30 minutes, whatever their volume.

Antacids are generally used to relieve dyspeptic symptoms and they are taken intermittently when symptoms occur. Side effects and inconvenience limit their use as ulcer healing agents.

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