GI - Drugs Used for Gastritis and 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

Sucralfate

Misoprostol

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 (EP_1-4)
  • 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