A Textbook of Clinical Pharmacology and Therapeutics

●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

CHAPTER 34

34 Alimentary system and liver

PEPTIC ULCERATION

PATHOPHYSIOLOGY

Peptic ulcer disease affects approximately 10% of the popula-
tion 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 ulcer-
ation in a 12-month period. Its aetiology is not well under-
stood, 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.

MUCOSAL RESISTANCE

Some endogenous mediators suppress acid secretion and pro-

tect the gastric mucosa. Prostaglandin E 2 (the principal

prostaglandin synthesized in the stomach) is an important

gastroprotective mediator. It inhibits secretion of acid, pro-

motes 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 salicyl-

ate, 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 defect-

ive. The presence of strong acid in the submucosa causes fur-

ther damage, and persistence of Hions in the interstitium

initiates or perpetuates peptic ulceration. Hions 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 mech-

anism 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 dam-

age to the gastric mucosa.

HELICOBACTER PYLORI

The presence of the bacterium Helicobacter pylorihas now been

established as a major causative factor in the aetiology of pep-

tic 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. pyloriis

present in all patients with active type B antral gastritis and in

90–95% of those with duodenal ulcers. After exclusion of gas-

tric ulcers caused by non-steroidal anti-inflammatory drug

therapy and Zollinger–Ellison syndrome, the incidence of

H. pyloriinfection in patients with gastric ulcer approaches

100%. The strongest evidence of a causal relationship between

H. pyloriand peptic ulcer disease is the marked reduction in

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 pylorior
  NSAID therapy.


• Relapse is common.

ACID–PEPSIN SECRETION

Gastric parietal (oxyntic) cells secrete isotonic hydrochloric
acid. Figure 34.1 illustrates the mechanisms that regulate gas-
tric 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 gastrin-
secreting adenoma associated with very severe peptic ulcer
disease.

CONTRIBUTION BY DR DIPTI AMIN