CPT22 - GI Pharmacology

Question 1

4 pharmacokinetic/dynamic features of PPIs

Pro-Drug
Enteric Coating
Weak Bases
Metabolism and Excretion

Answer 1

1. ) Pro-Drug - activated in acidic conditions
   - in the canaliculus of the parietal cell (pH < 4)
2. ) Enteric Coating - needed for oral forms
   - prevents premature activation in the stomach
3. ) Weak Bases - accumulate in the acidic space of the secretory canaliculus in a stimulated parietal cell
   - high conc in luminal surface of the parietal cell
4. ) Metabolism and Excretion
   - metabolised by the liver (CYP2C19 and CYP3A4)
   - excreted by the kidneys

Question 2

6 features of proton pump inhibitors (PPIs)

Examples x2
Mechanism
Usage x3
Caution/Contraindications x4
Side Effects x5
Complication

Answer 2

1.) Examples - omeprazole, lansoprazole

2. ) Mechanism - prevents acid secretion into stomach
   - irreversibly blocks H+/K+ pump on parietal cells

3.) Usage - GORDs, gastritis, peptic ulcer disease

4. ) Caution/Contraindication
   - osteoporosis, gastric cancer, elderly (STOPP)
   - can ↓ effectiveness of clopidogrel (use same CYPs)
5. ) Side Effects
   - abdominal pain, headache, N/V,
   - GI disorders, ↑risk of GI infections (e.g. C. diff)
6. ) Complication - increased levels of gastrin
   - parietal and ECL cell hyperplasia → carcinoid tumours

Question 3

6 features of histamine H2 antagonists

Examples x2
Mechanism x2
Pharmacodynamics x2
Usage x3
Caution/Contraindications x2
Side Effects x4

Answer 3

1.) Example - ranitidine, cimetidine

2. ) Mechanism - indirectly inhibits parietal cells
   - reversibly blocks H2 receptors on parietal cells
   - this ↓vesicular fusion to the caniclulus
   - also reduces cAMP –> ↓activity of the H/K pump
3. ) Pharmacodynamics
   - rapidly absorbed from the small intestines
   - excreted by the liver and the kidneys

4.) Usage - GORDs, gastritis, peptic ulcer disease

5. ) Caution/Contraindications
   - can ↓ketoconazole absorption (due to less acidity)
   - cimetidine inhibits CYPs which can lead to toxic levels of other drugs e.g. warfarin, lidocaine, phenytoin
6. ) Side Effects
   - diarrhoea, constipation, muscle ache, fatigue

Question 4

4 effects of prostaglandins in the GI system on ….

Blood Flow
Acidity x2
Mucus and HCO3- Secretion
Inflammatory Mediators

Answer 4

1. ) Potent Vasodilators - ↑ blood flow to the GI tract
   - this can help promote ulcer healing
2. ) Reduce Acidity
   - reduces acid secretion at relatively high levels
   - prevents backflow of acid by reducing the permeability of the epithelium
3. ) Stimulate Mucus and HCO3- Secretion
   - in the stomach and elsewhere in the GI tract
4. ) Reduce Release of Inflammatory Mediators
   - so they will not contribute to mucosal injury

Question 5

5 features of prostaglandin analogues

Example 
Mechanism
Usage x2
Contraindication x1
Side Effects x2

Answer 5

1.) Example - misoprostol

2. ) Mechanism - ↑PGE2 which ↓H/K pump activity
   - similar to H2 antagonists as it reduces cAMP
3. ) Usage - NSAID induced ulcers
   - can also be used in post-partum haemorrhage
4. ) Contraindication - pregnancy
   - causes uterine contractions –> abortion
5. ) Side Effects
   - diarrhoea and abdominal pain

Question 6

3 features of antacids (e.g gaviscon)

Examples
Mechanism
Usage

Answer 6

1.) Examples - aluminium hydroxide, alginic acid

2. ) Mechanism - neutralise HCl in gastric secretions
   - also combines with bicarbonate to inhibit reflux

3.) Usage - symptom relief for dyspepsia (indigestion)

Question 7

Management of GORD

Lifestyle x6
GORD Exacerbating Medication (name 6)
Proton Pump Inhibitors (PPIs) x2
Histamine H2 Antagonists 
Surgery

Answer 7

1. ) Lifestyle
   - weight loss, avoiding trigger foods
   - ↓alcohol/caffeine, stop smoking
   - eating smaller meals, eating earlier
2. ) GORD Exacerbating Medication - consider removing
   - alpha-blockers, ß-blockers, CCBs
   - anticholinergics, antidepressants (tricyclic), NSAIDs
   - corticosteroids, theophyllines, nitrates
   - benzodiazepine, bisphosphates
3. ) PPIs - omeprazole, lansoprazole
   - provides rapid relief and healing in >80%
   - can also do a test for H.pylori
4. ) H2 Antagonists - ranitidine
   - can be added if PPIs are ineffective
5. ) Surgery - fundoplication
   - if medications do not work

Question 8

Management of Gastritis

Acute (erosive) Gastritis
Chronic (non-erosive) Gastritis
Autoimmune Gastritis

Answer 8

1. ) Acute Gastritis - causes: NSAIDs, alcohol, bile
   - reduce or stop irritants
   - add PPI or H2 antagonists
2. ) Chronic Gastritis - caused by H pylori
   - triple therapy: PPI + amoxicillin + (clarithromycin or metronidazole), works in 70-80% of people
   - quadruple therapy: PPI + x2 antibiotics + bismuth
3. ) Autoimmune Gastritis
   - long term cyanocobalamin (vit-B12) treatment

Question 9

Management of peptic ulcer disease

PPI or H2 Antagonist
Stop NSAIDs
Misoprostol
H Pylori Eradication (CLAMP)

Answer 9

1.) PPI or H2 Antagonist

2. ) Stop NSAIDs - improves prostaglandin synthesis
   - can use COX-2 inhibitor (celecoxib) which doesn’t affect COX-1 mediated prostaglandin synthesis
3. ) Misoprostol - prostaglandin analogue
   - last line: used if you need to continue NSAIDs
4. ) H Pylori Eradication - triple therapy
   - 7 days of PPI + amoxicillin + clarithromycin (all BD)
   - metronidazole if penicillin allergic