A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

CHAPTER 34
ALIMENTARY SYSTEM AND LIVER
CONTRIBUTION BY DR DIPTI AMIN
● Peptic ulceration 247
● Oesophageal disorders 252
● Anti-emetics 253
● Inflammatory bowel disease 255
● Constipation 256
● Diarrhoea 258
● Irritable bowel syndrome 259
● Pancreatic insufficiency 259
● Liver disease 260
● Drugs that modify appetite 262
PEPTIC ULCERATION
PATHOPHYSIOLOGY
Peptic ulcer disease affects approximately 10% of the population
of western countries. The incidence of duodenal ulcer
(DU) is four to five times higher than that of gastric ulcer (GU).
Up to 1 million of the UK population suffer from peptic ulceration
in a 12-month period. Its aetiology is not well understood,
but there are four major factors of known importance:
1. acid–pepsin secretion;
2. mucosal resistance to attack by acid and pepsin;
3. non-steroidal anti-inflammatory drugs (NSAIDs);
4. the presence of Helicobacter pylori.
Key points
Peptic ulceration
• Affects 10% of the population.
• Duodenal ulcers are more common than gastric ulcers
(4:1).
• Most gastric ulcers are related to Helicobacter pylori or
NSAID therapy.
• Relapse is common.
ACID–PEPSIN SECRETION
Gastric parietal (oxyntic) cells secrete isotonic hydrochloric
acid. Figure 34.1 illustrates the mechanisms that regulate gastric
acid secretion. Acid secretion is stimulated by gastrin,
acetylcholine and histamine. Gastrin is secreted by endocrine
cells in the gastric antrum and duodenum. Zollinger–Ellison
syndrome is an uncommon disorder caused by a gastrinsecreting
adenoma associated with very severe peptic ulcer
disease.
MUCOSAL RESISTANCE
Some endogenous mediators suppress acid secretion and protect
the gastric mucosa. Prostaglandin E 2 (the principal
prostaglandin synthesized in the stomach) is an important
gastroprotective mediator. It inhibits secretion of acid, promotes
secretion of protective mucus and causes vasodilatation
of submucosal blood vessels. The gastric and duodenal
mucosa is protected against acid–pepsin digestion by a mucus
layer into which bicarbonate is secreted. Agents such as salicylate,
ethanol and bile impair the protective function of this
layer. Acid diffuses from the lumen into the stomach wall at
sites of damage where the protective layer of mucus is defective.
The presence of strong acid in the submucosa causes further
damage, and persistence of H ions in the interstitium
initiates or perpetuates peptic ulceration. H ions are cleared
from the submucosa by diffusion into blood vessels and are
then buffered in circulating blood. Local vasodilatation in the
stomach wall is thus an important part of the protective mechanism
against acid–pepsin damage.
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Aspirin and other NSAIDs inhibit the biosynthesis of
prostaglandin E 2 , as well as causing direct irritation and damage
to the gastric mucosa.
HELICOBACTER PYLORI
The presence of the bacterium Helicobacter pylori has now been
established as a major causative factor in the aetiology of peptic
ulcer disease. Although commonly found in the gastric
antrum, it may also colonize other areas of the stomach, as well
as patches of gastric metaplasia in the duodenum. H. pylori is
present in all patients with active type B antral gastritis and in
90–95% of those with duodenal ulcers. After exclusion of gastric
ulcers caused by non-steroidal anti-inflammatory drug
therapy and Zollinger–Ellison syndrome, the incidence of
H. pylori infection in patients with gastric ulcer approaches
100%. The strongest evidence of a causal relationship between
H. pylori and peptic ulcer disease is the marked reduction in