Pharmacology 17 – Treatment of Stomach and Duodenal

Pharmacology 17 - Treatment of Stomach and Duodenal Ulcers
Anil Chopra
Describe the factors that impinge on the development of peptic ulcer disease.
Explain why antibiotics feature prominently in the treatment of peptic ulcer
Using named examples, explain, with the use of a clearly labelled diagram, the
mechanisms by which proton pump inhibitors and histamine (H2) receptor
antagonists promote the healing of gastric ulcers
Explain why misoprostol may be used in the treatment of iatrogenic peptic
ulcer disease.
Describe the mechanisms by which sucralphate and bismuth chelate are
thought to be useful anti-ulcer drugs.
Provide two examples of ‘triple therapy’ for peptic ulcer disease.
What do you understand by the term ‘gastroesophageal reflux disease’ and
how may it be treated?
There are a number of different factors which protect the gastric and duodenal
- mucus produced in gastric and duodenal mucosa
- HCO3- ions trapped in mucus generate a pH of 6-7 at mucosal surface
- Prostaglandins stimulate the production of bicarbonate inhibit gastric
The potential things that can degrade the mucosa include acid from the parietal cells
and pepsinogen from the chief cells. When the processes are unbalanced then gastric
and duodenal ulcers can form.
Causes of Peptic Ulcer Disease
 Helicobacter pylori infection
 Increased acid secretion
 Reduced bicarbonate secretion
 Reduced thickness of the mucosal layer
 Increase in pepsin type 1
 Decreased mucosal blood flow
Risk factors: genetic predisposition, stress, smoking
Prevalence: 1:10 of the population in developed countries
Name – metronidazole, amoxicillin, clarithromycin, clarithromycin, bismuth
Usage – to eliminate Helicobacter pylori (gram negative bacterium). The majority of
patients with peptic ulcers are infected with the bacterium. A single antibiotic is not
normally used – “triple therapy” is often adopted.
Rationale for use:
 50-80% of population chronically infected
 10-20% of which go on to develop peptic ulcers or neoplasia
 100% of patients with gastric cancer and 80-90% with ulcers are infected
Routes of transmission of infection unsure – possibly animals/faeces or
socioeconomic conditions
 Aim for 90% eradication in 7-14 days, eradication difficult – if part of treatment
then recurrence falls from 80% to 5%
Mode of Action & Side effects – see lecture on antibiotics
Inhibitors Of Gastric Acid Secretion
Proton Pump Inhibitors
Name – omeprazole
Usage – component of triple therapy used in peptic ulcers resistant to H2 antagonists
as well as reflux oesophagitis
Mode of Action – it inhibits gastric acid secretion by parietal cells by 90%. They are
irreversible inhibitors of the H+/K+ ATPase and is inactive at a neutral pH. It
accumulates in the canaliculi of the parietal cells which minimizes its effect on ion
pumps elsewhere in the body.
Side Effects & Pharmacokinetics
- Orally active with few side effects.
- Administered as enteric coated slow release formation.
Histamine type 2 H2 receptor Antagonists
Names - cimetidine, ranitidine
Usage – gastric and duodenal ulcers
Mode of Action – inhibit gastric acid secretion by 60%. They are antagonists at
histamine type 2 receptors on parietal and chief cells.
Side Effects and Pharmacokinetics - Orally active with few side effects although both
inhibit P450 metabolism
Antimuscarinics are also used.
Cytoprotective Drugs
Names – sucralphate
Usage – gastric duodenal ulcers
Mode of Action – it is a polymer containing aluminium hydroxide and sucrose
octasulphate that acquires a strong negative charge in an acid environment which then
binds to positively charged groups on proteins and polymers. This produces gel-like
substances which coat and protect the ulcer and limit the pepsin degradation of
mucus. It also increases prostaglandin, mucus and HCO3- secretion and reduces the
number of H. pylori.
Side Effects and Pharmacokinetics
• Orally administered drug and therefore remains in G.I tract.
• May cause constipation
• Reduces absorption of some other drugs (e.g. antibiotics & digoxin)
Names – bismuth chelate
Usage – triple therapy
Mode of Action & Side Effects and Pharmacokinetics -Same way as sucralphate
Name - Misoprostol
Usage – with NSAIDs when prescribed chronically & in gastric and duodenal ulcers.
Mode of Action – it mimics the action of locally produced PG to maintain the
gastroduodenal mucosal barrier.
Side Effects - diarrhoea, abdominal cramps, uterine contractions. Do not use in
Triple Therapy
Triple therapy better than single drug therapy due to resistance:
Example 1:
o Metronidazole (useful against anerobic bacteria) or amoxycillin (broad
spectrum) – depends on local pattern of resistance
o Clarithromycin – antibiotic with macrolide structure, prevents
translocations of bacterial tRNA
o Proton Pump Inhibitor (PPI) – improves antibiotic efficiency by
increasing gastric pH – improves stability and absorption
Example 2:
o H2 receptor antagonist
o Clarithromycin
o Bismuth
Problems with triple therapy:
Development of resistance
Adverse response to alcohol –especially metronidazole (interferes with
Name – generally salts of magnesium Mg2+ and aluminium Al3+
Usage – non-ulcer dyspepsia, and GORD (gastro-oesophageal reflux disease)
Mode of Action - neutralises acid, raises gastric pH, reduces pepsin activity
GORD – gastroesophageal reflux disease
 Stomach and duodenal contents reflux into oesophagus
 Causes oesophagitis, chronically progressing to premalignant mucosal cells and
potential oesophageal Adenocarcinoma
 Occasional and uncomplicated GORD:
 Heart burn
 May treat by self medication with antacids and H2 receptor antagonists
 Can also be treated with PPI’s
 Combine with drugs that increase gastric motility and stomach emptying – e.g. D2
receptor antagonists such as metaclopramide