Gastric & Peptic ulcer

Question 1

List THREE classes of agents that reduce gastric acidity.

Answer 1

Antacids
H2‐receptor Antihistamines
Proton Pump Inhibitors (PPI)

Question 2

List THREE examples of mucosal protective agents

Answer 2

1. Sucralfate
2. Misoprostol
3. Bismuth Compounds

Question 3

Rank common antacids according to their rate of neutralization.

Answer 3

NaHCO3> CaCO3> Mg(OH)2> Al(OH)3

Question 4

Why is simethicone often found in antacid formulations?

Answer 4

Antifoaming activity coalesces bubbles and reduces bloating.
Helps to reduce gastric distention, belching discomfort side effects.

Question 5

Why are magnesium and aluminium compounds usually formulated together in antacids?

Answer 5

Magnesium causes osmotic diarrhoea
Aluminum causes constipation
Together the effects balance

Question 6

List adverse effects of antacids.

Answer 6

• Sodium compounds: Fluid retention, hypertension, caution in heart failure
• Sodium bicarbonate: may cause sodium overload, alkalosis on long term usage
• Calcium compounds: Hypercalcaemia, rebound acid secretion, renal stones (calcium phosphate precipitate)
• Carbonates and bicarbonates: CO2 gas formation resulting in gastric distention, belching
• Magnesium compounds: Osmotic diarrhoea
• Aluminium compounds: Constipation
• Avoid long-term use in patients with renal insufficiency
• Affect absorption of other medications
  => Do not take within 2 hours of other medication

Question 7

Name an example of an H2 antihistamine

Answer 7

Cimetidine, ranitidine, famotidine

Question 8

When is the best time to take H2 antihistamines?

Answer 8

Effective in controlling fasting and nocturnal acid release. As many patients with peptic ulcers have elevated nocturnal acid release, usually taken on an empty stomach before sleep at night.

Question 9

List adverse effects of H2 antihistamines.

Answer 9

Common: constipation, headaches
Uncommon: agitation

Question 10

List adverse effects of cimetidine.

Answer 10

Mental confusion in elderly, critically ill patients, or renal/hepatic dysfunction

Anti-androgenic: inhibits estradiol metabolism, increases serum prolactin
- Men: gynaecomastia, impotence
- Women: galactorrhoea

Inhibits CYP450 (2D6, 1A2) increasing plasma
- Prolongs half-life of other drugs e.g., anti-depressants, warfarin, theophylline, paracetamol, caffeine
- Similar interactions not significant with other H2 antihistamines e.g., ranitidine, famotidine

Question 11

Name ONE example of a proton-pump inhibitor

Answer 11

Omeprazole, esomeprazole, and other *prazole

Question 12

Briefly describe the mechanisms of action of PPIs that result in selective proton pump inhibition in the parietal cell canaliculi

Answer 12

• Inactive pro-drugs (absorbed well)
• Enteric-coated formulation (protect from gastric acid)
• Released and absorbed in intestines
• Protonated, activated and concentrated in parietal cell canaliculi
• Reactive thiophilic sulphenamide active drug (not absorbed well)
• Forms covalent disulphide bonds with H+-K+-ATPase (irreversible)
• Inhibits gastric acid secretion

Question 13

Briefly describe the duration of action of omeprazole.

Answer 13

Plasma T½ 1h but effective for 18-24 h due to irreversible inhibition of proton pumps

3-4 days before full inhibition of all proton pumps.

4-5 days after drug withdrawal to return to pre-treatment acid level due to time required to synthesize new proton pump

Question 14

When is the best time to take PPIs?

Answer 14

Inhibits active pumps, not quiescent pumps
- Best to be present during mealtimes

Short serum T1/2 = 1-2hr; Tmax = 2-4hr
- Given 1hr before meal

Bioavailability decreased 50% by food
​- Given on empty stomach (usually before breakfast)

Question 15

List adverse effects of omeprazole.

Answer 15

Nausea, diarrhoea, colic, headache, dizziness
Reduced gastric acid barrier –bacterial overgrowth
Skin rashes
Transient increase in hepatic aminotransferase occasionally
Inhibition of metabolizing enzyme CYP450 2C19
=> increasing diazepam concentrations

Question 16

Briefly describe the properties and mechanisms of action of sucralfate

Answer 16

Salt of sucrose complexes to sulphated Al(OH)3

Highly insoluble therefore no systemic effects

Breaks down to sucrose sulphate (strong negative charge) + aluminium salt

Mechanism of action:
- Negatively charged sucrose sulphate binds positively charged proteins at ulcer crater forming a viscous, tenacious gel that prevents further acid attack
- Stimulates mucosal prostaglandin and bicarbonate secretion

Question 17

Briefly describe the clinical use and adverse effects of sucralfate

Answer 17

Adminstered on empty stomach (at least 1hr before meals)

Limited use for ulcers today as PPIs are more effective
- Still used for prevention of stress-related bleeding in critically ill patients

Adverse effects:
- Few as insoluble and not systemically absorbed
- Constipation
- Impairs absorption of other drugs e.g., theophylline, digoxin

Question 18

Briefly describe the mechanisms of action of bismuth compounds as mucosal protective agents.

Answer 18

Mechanisms of action:
- Bismuth forms a protective layer protecting ulcers from acid and pepsin
- Stimulates mucus and bicarbonate secretion
- Directly anti-microbial activity against H. pylori

Question 19

Briefly describe the adverse effects of bismuth compounds

Answer 19

Although > 99% of bismuth is eliminated in stool <1% is absorbed and stored in many tissues, elimination is by slow renal excretion

Prolonged use may rarely produce bismuth toxicity resulting in encephalopathy (ataxia, headaches, confusion, seizures)
- Use only for short periods
- Avoid in patients with renal insufficiency

But bismuth compounds generally have a good safety profile when used short-term for ulcers

Harmless blackening of stool and reversible darkening of tongue

Question 20

Why is use of misoprostol limited?

Answer 20

Limited use today due to:
Adverse effects
Multiple daily dosing (non-compliance)
Advent of COX-2 selective NSAIDs
Potential for abuse as an abortifacient

Question 21

List adverse effects of misoprostol.

Answer 21

Adverse Effects:
Abdominal pain/cramps
Diarrhoea
Abortion (uterine contraction)
Bone pain and hyperostosis (excessive bone growth)

Question 22

Explain the properties and mechanisms of action of misoprostol

Answer 22

Synthetic PGE1 analogue

Rapidly absorbed after oral dosing

Short T1/2 = 30 min; must be given 3-4 times per day

Indications
- Prevention of NSAID-induced peptic ulcers

Mechanisms of action:
- Binds to PGE2 receptors (EP1-4)
- Low dose (cytoprotective): promotes bicarbonate and mucus secretion, enhances mucosal blood flow
- High dose (antisecretory): inhibits gastric acid secretion

Question 23

What is triple therapy?

Answer 23

Two antibiotics + 1 PPI (7-14 days)

• Antisecretory Agent e.g., Omeprazole OR Esomeprazole
• Antibiotics: Clarithromycin PLUS Amoxicillin OR Metronidazole (in patients allergic to penicillins)

Question 24

What is the role of PPI in triple therapy?

Answer 24

Mechanisms of PPI in triple therapy:
- Direct antimicrobial properties (minor)
- Raises intra-gastric pH (pH3.5 – 5.5) lowering minimum inhibitory concentration (MIC) of the antibiotics against H. pylori

After completion of triple therapy, the PPI is continued for 4-6 weeks to ensure complete healing

Question 25

What is quadruple therapy?

Answer 25

Second-line “quadruple therapy” (useful in areas of high prevalence of resistance to clarithromycin or metronidazole)
1 Bismuth + 2 antibiotics (metronidazole+tetracycline) + 1 PPI (10-14 days)

Question 26

List adverse effects of triple therapy

Answer 26

Common side effects are diarrhoea, nausea and vomiting