Pharmacology of upper and lower GI tract drug treatments

Question 1

What cell secretes Gastric acid and is responsible for ulceration and inflammation?

Answer 1

Parietal cell

Question 2

What are the four controls of acid secretion?

Answer 2

1) ACH (Vagal nerve control)
2) H2 receptor (Histamine)
3) Gastrin (triggered by diet)
4) PGE2 (prostaglandin)
- only prostaglandin decreases acid release rest increase
- Each affect H+/K+ ATPase proton pump

Question 3

What is a peptic ulcer?

Answer 3

Defect in the gastric or duodenal mucosa caused by an increase in acid secretion

Question 4

What are the three things that need to be done when treating peptic ulcer?

Answer 4

1) pain relief
2) Heal Ulcer
3) Prevent relapse or complications
4) Ensure not gastric carcinoma

Question 5

What are the five treatments types for peptic ulcers?

Answer 5

1) Remove irritants (drugs or dietary)
2) Antacids
3) Proton Pump inhibitors
4) H2 receptor antagonists
5) Antibiotics (if H Pylori present)

Question 6

How can NSAIDs cause ulceration?

Answer 6

• NSAIDs act on COX1 and COX2
• COX1 responsible for prostaglandin synthesis
• when inhibited by NSAIDs Prostaglandin can’t decrease acid secretion

Question 7

What are the other major causes of Ulceration?

Answer 7

1) Aspirin
2) Corticosteroids
3) Bisphosphonates (mucosal toxic)
4) Nicotine
5) Alcohol
6) Caffeine
7) Severe stress (increases acid sec)
8) Hypersecretory states (uncommon)

Question 8

What bacteria can cause Ulcers?

Answer 8

Helicobacter Pylori

Question 9

What are the most common antacids?

Answer 9

Magnesium and aluminium salts often combination

Question 10

What are the disadvantages of antacid use?

Answer 10

1) only symptomatic relief won’t actually decrease acid over production so only effective briefly
2) Antacids which are too well absorbed can metabolic alkalosis in blood

Question 11

What are the main Proton Pump Inhibitors?

Answer 11

• Omeprazole (irreversible)
• Lansoprazole
• Pantoprazole
• Esomeprazole

Question 12

What is the MOA of Proton pump Inhibitors?

Answer 12

Inhibit H+/K+ Proton pump in parietal cells to prevent acid secretion

Question 13

What are the adverse reactions of omeprazole?

Answer 13

Common: GI disturbance (vomiting, diarrhoea or constipation) and headaches
Important: Inc risk of C Diff and pneumonia, hyponatraemia, hypomagnesaemia, CKD, liver problems and blood disorders e.g. dec platelets or WBCs

Question 14

What drugs does omeprazole interact with

Answer 14

1) Warfarin = increases anticoagulant effects as CYP450 enzyme inhibited so warfarin not metabolised
2) Clopidogrel = less activated as hepatic pro-drug, reduce anti platelet effects

Question 15

Why might PPIs be contraindicated?

Answer 15

1) reduction in efficacy of clopidogrel but lansoprazole can be used instead (less CYP450 inhibition) usually necessary in post NSTEMI patients
2) Can get rebound effect where cells secrete more cells in response to drugs but shorter treatment times decrease likelihood

Question 16

What are the common H2 receptor antagonists?

Answer 16

Cimetidine

Ranitidine

Question 17

What do H2 Receptor antagonists target?

Answer 17

Target Histamine receptor so reduce histamines signalling and less acid secreted

Question 18

What are the adverse side effects of Cimetidine?

Answer 18

Gynaecomastia in men
confusion in older patients
Diarrhoea
Potent CYP450 inhibitor so doesn’t interact well with other drugs, any CYP450 metabolised drugs not processed well so many side effects

Question 19

Why may Ranitidine be preferred over Cimetidine?

Answer 19

1) less potent inhibitor so less interactions
2) No gynaecomastia or confusion
3) But do contain microscopic traces of carcinogens so aren’t used much

Question 20

Pathology of H Pylori?

Answer 20

Found in mucous layer and secrete urease which converts urea to ammonia and CO2, these products cause inflammation and erode mucosal layer

Question 21

What is the test for H pylori?

Answer 21

• Use Carbon-13 urea breath test
• Give sample of Urea labelled with C13
• take breath sample 30 mins later, if C13 present in CO2 the positive test
• serology test will show pos test even if recovered
• GI endoscopy also possible Pink if pos

Question 22

Treatment for H Pylori?

Answer 22

• Eradication therapy which involves two antibiotics and a PPI/H2 receptor antagonist
• for 7 days but can need for a little longer

Question 23

What antibiotics are usually used in the eradication therapy?

Answer 23

Clarithromycin

Amoxicillin or metronidazole

Question 24

When should an urgent upper GI endoscopy be done?

Answer 24

Red flag symptoms: GI bleed, Weight loss, dysphagia and vomiting
GI bleed may only show as anaemia if chronic
be more wary of those over 55

Question 25

What are the non-pharmacological treatments for constipation?

Answer 25

• increase fluid
• increase fibre intake
• increase mobility
• stop constipating drugs

Question 26

What are the constipating drugs?

Answer 26

Opioids
anti-muscarinics e.g. anti-depressants
diuretics

Question 27

What are non-drug causes of constipation?

Answer 27

• Pain when passing bowel motions e.g. haemorrhoids
• Hypercalcaemia
• Hyperthyroidism
• Diabetes
• Tumours

Question 28

What are the four types of laxative

Answer 28

• Bulk (Fybrogel) make stool soft and easy to pass
• Stimulant (Senna) stimulate enteric nervous system to promote peristalsis
• Osmotic (Macrogels) pull water into gut lumen
• Faecal softener (docusate) less commonly used

Question 29

How is constipation treated?

Answer 29

• Try non-pharm first
• Pre-empt if giving opioids give osmotic and stimulant (not bulk)
• First line usually Bulking and osmotic