Key Topics

• • Overview
• • Gastric acid-related conditions
• • Anti-emetics
• • Diarrhoea and constipation
• • Inflammatory bowel disease

Learning Objectives

• • To understands the key anatomical components of the gastrointestinal tract and their relevant pharmacology
• • To have knowledge of the common side effects of drugs acting on the gastrointestinal tract and their relevance to prescribing in dentistry
• • To be aware of importance of immunosuppression in inflammatory bowel disease and its relevance to dentistry

Introduction

The gastrointestinal tract’s (GIT) main function is that of digestion and absorption of food. It is also one of the major endocrine systems of the body. There is a wide range of gastrointestinal disorders that have oral manifestations and impact on a patient’s oral health.

The GIT and its relevant pharmacology can be divided into the stomach and gastric acid-related conditions, management of nausea and vomiting, constipation and diarrhoea, irritable bowel syndrome, the management of inflammatory bowel disease and the medical management of gallstones. There are also many drugs that adversely affect gastrointestinal function (see Table 21.1).

Gastric acid-related conditions

Gastric acid has many purposes including providing an optimal environment for proteolytic enzymes to work and improving the sterility of the stomach contents. It is controlled by local and systemic endocrine effects.

Acid secretion from parietal cells is increased by:

• Acetyl choline from the vagus nerve
• Histamine from local nerve endings acting on histamine type II receptors
• Gastrin secreted by the antrum of the stomach.

The exact mechanism of action of these three stimulants on the parietal cell is unclear.

Acid secretion is decreased by:

• Prostaglandin receptors on the luminal surface of the cell.

All of these mechanisms work on the ‘proton pump’ and gastrin provides a negative feedback: an acid environment in the stomach decreases gastrin output thus shutting down acid secretion.

Peptic ulcers

In peptic ulceration there is an imbalance in the protective elements (mucus secretion, gastric blood flow) and harmful elements (acid, exotoxins, drugs). Complications include pain, anaemia, severe bleeding, perforation and pyloric stenosis (caused by fibrosis following inflammation).

Duodenal ulcers:

Duodenal ulcers are often associated with high acid output and Helicobacter pylori infection. They have no malignant potential. They can be cured by acid suppression but have a high recurrence rate. This can be reduced by eradication of H. pylori.

Gastric ulcers:

These are often associated with low or normal acid output and the use of non-steroidal anti-inflammatory drugs. They are sometimes related to H. pylori infection. They have a risk of malignant transformation.

Medications used in gastric acid-related conditions

Antacids

These reduce gastric acidity and thus diminish the activity of gastric pepsin. They can relieve the pain of peptic ulceration; however they do not promote healing unless large doses are given frequently. Antacids are generally not toxic, but large doses can lead to side effects: sodium bicarbonate in large doses can cause alkalosis and calcium carbonate in excess can induce hypercalcaemia. For this reason, magnesium and aluminium compounds are preferred such as magnesium carbonate and aluminium hydroxide.

Helicobactor pylori eradication

H. pylori is spread by the faeco-oral route. It is associated with over 95% of duodenal ulcers and 70% of gastric ulcers. H. Pylori colonizes the antrum of the stomach, where it secretes urease, creating an alkaline microenvironment to protect itself. It interferes with normal control of acid secretion and also secretes exotoxins which directly damage the mucosa. Eradication of H. pylori can be achieved using a combination of a proton pump inhibitor (e.g. omeprazole) and two antibiotics (e.g. clarithromycin and amoxicillin).

Acid secretion reducing drugs

Histamine receptor antagonists:

These drugs, such as cimetidine and ranitidine, work as histamine antagonists at H2 receptors. They decrease acid secretion and aid in healing duodenal ulcers. They can be used in the treatment of reflux oesophagitis and they relieve symptoms of dyspepsia.

These drugs have several adverse effects: cimetidine has a weak anti-androgen effect and can cause gynaecomastia in long-term use. They can cause confusion and drowsiness particularly in the elderly. Cimetidine is a liver enzyme inhibitor and may increase the effects and toxicity of other drugs.

Proton pump inhibitors:

These drugs, such as omeprazole or lansoprazole, irreversibly inhibit the H+/K+ ATPase enzyme (proton pump) and so reduce acid secretion. They aid healing of acid-related disorders. They may be used long term in reflux oesophagitis and in high doses they are used in the treatment of Zollinger-Ellison syndrome. Side effects include headache, nausea, vomiting and diarrhoea.