6. Gastrointestinal Disease

Question 1

What is H.Pylori?

Answer 1

= Helicobacter pylori  Gram negative bacteria that can live in stomach and duodenum

• Stimulates the secretion of gastrin and leads to a ‘hypergastrinemia’ state  excess gastrin leads to increased gastric acid secretion, inflammation and ulceration
• Weakens protective mucous coating of the stomach and duodenum  acid and H pylori irritate lining causing ulcer
• ## neutralises acid in the stomach, allowing H pylori to survive

Question 2

What is the test for H.Pylori?

Answer 2

= Urea breath Tests

Question 3

First line treatment for H.pyloi eradication?

Answer 3

= Triple therapy: 1 PPI and 2 antibiotics for 7 days

Eg. Esomeprazole 20mg bd (Nexium)
Clarithromycin 500mg bd (Klacid)
Amoxicillin 1g bd (Amoxil)

• If amoxicillin unsuitable replace with 400mg metronidazole bd
• High prevalence of side effects (nausea, diarrhoea, taste disturbances)

Question 4

What is the role of H.Pylori eradication prior to NSAID use?

Answer 4

• Patients with history of ulcer disease should be tested and treated for H.Pylori infection before regular NSAID use because eradication for pylori reduces the risk of ulcer and bleeding

Question 5

What is PPIs and what is their mechanism of action?

Give examples

Answer 5

= Protein Pump inhibitors

PPI ‘kill off’ (inactivate) the PP in parietal cells so that there is no longer acid produced

o Acid production obliterated for 24-48 hours

• digestion of some nutrients (ie B12 and calcium) is affected as they require HCl to digest, so supplements are given for digestion without HCl

Examples: Omeprazole, Lansoprazole, Esomeprazole, Rabeprazole

Question 6

Risks of Long term PPI use?

Answer 6

Increase risk of:

o Enteric infections
o Pneumonia
o Decrease serum B12
o Fracture (due to decreased calcium carbonate absorption) and osteoporosis

Question 7

It is important that treatment with PPI is reviewed regularly and where possible:

Answer 7

o Stop treatment
o Use intermittently when symptoms develop
o Step down to low-dose therapy

Question 8

Mechanism of action H2 antagonists?

Answer 8

= Competitively block H2 receptors on parietal cells of stomach and so reduce acid secretion

o Available OTC
o e.g. Ranitidine

o Not P450 inhibitor

o Cimetidine

Question 9

CYP P450 Enzyme

Answer 9

o CYP metabolise drugs
o Drugs that inhibit enzyme means that it can no longer metabolise the drugs it is meant to, so this causes an increase in that drug within the body  toxicity

o Eg. Warfarin + cimetidine  cimetidine inhibits P450 which metabolises warfarin  warfarin toxicity (pharmacokinetic interaction)

Question 10

What is GORD

Answer 10

= The acidic stomach contents enter the oesophagus and in some causes the throat and the mouth.

o Exposure of the oesophagus to refluxed gastric contents results in

o Heartburn, acid regurgitation

o More severe symptoms: difficulty swallowing, chest pain

o Complications include oesophageal erosions, oesophageal ulcer and narrowing of the oesophagus (oesophageal stricture)
o In some patients the normal oesophageal lining may be replaced with abnormal (Barrett’s) epithelium which is linked to oesophageal cancer

Question 11

Mechanism of action GORD

Answer 11

• GORD is related to disturbance of normal anti-reflux mechanisms
• Lower oesophageal sphincter (LOS) tone plays an important in anti-reflux mechanisms
• Hiatus hernia (HH) may be the cause in some cases

Question 12

Causes of GORD?

Answer 12

Lower oesophageal sphincter (LOS) tone may be reduced by:

• Muscle weakness
• Abdominal distension
• Smoking
• Alcohol
• Certain foods and medications

Question 13

Consequences of GORD?

Answer 13

o Erosive oesophagitis
o Oesophageal stricture disease
o Barrett’ s oesophagus

Question 14

What is the aim of the management of GORD?

Answer 14

• Relieve symptoms, heal erosions or ulcerations, decrease recurrence and prevent complications

Question 15

Non-pharmacological management GORD

Answer 15

= life style changes

• Losing weight
• Avoiding triggering food and drunks
• Reducing portion sizes
• Avoid eating shortly before bed
• Sleep with head raised

Question 16

Pharmacological management of GORD

Answer 16

• Step Up  starry with low potency treatments and increase if necessary
  o Antacid/alginate > H2RA > PPI
• Step down  start with high potency treatments and decrease if possible
  o PPI> H2RA > Antacid/ alginate

Question 17

GORD management

Antiacid/alginate ?

Answer 17

= a base that neutralises the acid

Antacids (eg. Mylanta, Gaviscon)
o Neutralise gastric acid

o	Calcium carbonate, aluminium hydroxide, magnesium trisilicate

Adverse effects
o Constipation, diarrhoea (depending on base used)

o Symptomatic relief only and doesn’t prevent further episodes – usually have to be taken with every meal

Alginate combines with antacid to form a physical barrier (‘raft) to prevent stomach contents from flowing into oesophagus
o Gaviscon is a combination of both

EXAMPLES - Mylanta, gaviscon

Question 18

GORD management

H2 Antagonist

Answer 18

= decrease acid production
- Competitively block H2 receptors on parietal cells of stomach and so reduce acid secretion

o	Available OTC
o	Ranitidine 
o	e.g. Cimetidine

Adverse effects: sleeping difficulties, headache, diarrhea

Question 19

GORD management

Proton Pump Inhibitors (PPI)

Answer 19

= decrease acid production

-	Can still have wash up into oesophagus, but now the contents are less acidic

Adverse effects: constipation, abdominal pain, headache

Question 20

What is Peptic Ulcer Disease - PUD

Answer 20

= Occurs when ulcers are found in the stomach (gastric ulcers) or duodenum (duodenal ulcers)

Question 21

Symptoms of PUD

Answer 21

o Burning abdominal pain, often a few hours after eating, nausea & vomiting, weight loss, blood in vomit and stools in severe cases

Question 22

Cause of PUD

Answer 22

o Protective mucous layer of digestive tract is broken/compromised, so underlying tissue is exposed to acid

o H pylori induced ulcers and NSAID induced ulcers

Question 23

Contributory factors of PUD

Answer 23

o Gastric acid: needs to be present for ulcer to form

o Decreased blood flow: decrease in mucous and bicarbonate production (thus decreased protection from gastric juice)

o NSAIDS: inhibit production of prostaglandins which maintain mucosal layer

o Smoking: nicotine stimulates acid production

o Helicobacter pylori bacteria

Question 24

Management of PUD?

Answer 24

= NSAIDS

• Inhibit the synthesis of prostaglandins by inhibiting cyclo-oxygenase (COX)
  o Inhibition of COX-2: anti-inflammatory and analgesic action
  o Inhibition of COX-1: impaired gastric cytoprotection and antiplatelet effect
• Prostaglandins synthesised by COX-1 help maintains the protective lining of the stomach by:
  o Increasing bicarbonate ion secretion
  o Increasing mucous secretion
  o Increasing mucosal blood flow
  o Reducing gastric acid secretion

Question 25

Adverse effects of NSAID

Answer 25

Adverse effects: NSAID induced ulcers

• Related to dose and duration of use (high dose for long time = increased risk of ulcer)
• NSAID with longer half-life are more likely to cause GI complications