7. Treatment of peptic ulcers

Question 1

Describe the pathogenesis of Helicobacter infection

Answer 1

Produces urease which raises the gastric pH allowing H pylori to colonise
–>
Mucosal damage by bacterial mucinase etc
Inflammation by gastric acid, proteases and effector molecules
Mucosal cell death by cytotoxins and ammonia

Question 2

Inhibition of gastric secretion

Answer 2

• Food in the small intestine stimulates a reverse enterogastric reflex
• Reflex can also be initiated by
- distention of the small bowel
- acid in the upper intesting
- presence of protein breakdown products - irritation of the mucosa
• Secretin also opposes gastric secrtion

Question 3

H pylori infection consequences

Answer 3

Peptic ulcer disease
Gastric carcinoma
MALT lymphoma

Also: Dyspepsia, atrophic gastritis, iron deficiency anaemia, idiopathic thrombocytopaenic purport

Question 4

Role of helicobacter in peptic ulceration:
Acute infection?
Chronic infection?

Answer 4

Acute infection:
• Can cause acute infection with symptoms that include nausea, dyspepsia, malaise and halitosis
• Acute infection tends to last about two weeks
• Gastric mucosa is inflamed with neutrophils and inflammatory cells with marked persistent lymphocyte penetration
• Stomach acid production falls

Chronic infection:
• Local inflammation and gastritis
• Outcome depends on:
- pattern of inflammation 
- host response
- bacterial virulence
- environmental factors
- patient age

Question 5

Tests for diagnosis of H. pylori infection

Answer 5

Urea breath test
Stool antigen
Biopsy: Histology, rapid urease test, culture

Question 6

3 approaches to managing peptic ulcer disease?

Answer 6

1. Reducing the damage to the mucosal surfaces 
• dietary advice
• antacids
• bismuth
2. Killing H. pylori
3. Reducing gastric ascid
• proton pump inhibitors 
• H2 blockers

Question 7

What drugs are used in killing H, pylori?

Answer 7

PPI
Ampicillin

PLUS either clarithromycin or metronidazole
(If penicillin allergic then clarithromycin AND metronidazole)

Question 8

How are histamine blocked drugs used to reduce gastric acid in H. pylori treatment?

Answer 8

• Reduce gastric acid by reducing the stimulation of oxyntic cells via the histamine pathway
• Reduces gastric acid and permits ulcer healing
• Cimetidine was the first drug to show the value of this
approach
• Ranitidine followed and had a better safety profile

Question 9

What is the use of cimetidine in H pylori treatment?

Answer 9

H2 blocker so reduce gastric acid secretion
Oral
Renal excretion
Adverse event response:
-Causes dizziness
-Use P450 inhibitor. Affects hormone metabolism

Question 10

What is the use of Ranitidine in H pylori treatment?

Answer 10

H2 blocker
Oral
Renal excretion

Causes: Malaise and dizziness, liver toxicity, increased risk of GI infection

Question 11

Omeprazole use in H pylori:
Action?
Side effects?

Answer 11

Action:
Inhibits H+K+ATPase by binding irreversibly as the apical membrane. Hence K+ isn’t pumped into parietal cell and the H+ isn’t pumped out.
HCl can therefore not be formed.

Side effects: Headaches, dizziness, abdominal pain, diarrhoea, nausea, vomitting, rash

Question 12

If there is previous exposure to and penicillin allergy, what drugs are used in H pylori?

Answer 12

• Proton pump inhibitor
• bismuth
• metronidazole
• tetracycline

Question 13

If treatment of H pylori fails, what is the second line treatment?

Answer 13

Occurs 1/5

2nd line Tx:

• either an alternative regimen
• quadruple Tx (PPI+bismuth+2 antibx)