1. Drugs used in Gastritis & Peptic Ulcer Disease Flashcards
Types of drugs used in gastritis & peptic ulcer diseases
- Agents that reduce gastric acidity:
- antacids
- H2-receptor antagonists
- proton pump inhibitors - Mucosal protective agents
- sucralfate
- misoprostol
- bismuth compounds - Triple-therapy for H. Pylori eradication
- clarithromycin
- amoxicillin/metronidazole
- omeprazole
Examples of antacids
NaHCO3, CaCO3, Mg(OH)2, Al(OH)3
Rate of neutralisation of antacids
NaHCO3 > CaCO3 > Mg(OH)2 > Al(OH)3
Why do some antacids contain simethicone?
Simethicone is a anti-forming agent → eases release of gas within the GI tract via burping or flatulence
Adverse effects of antacids
- Na+ → Fluid retention, hypertension, CHF
- Ca2+ → Hypercalcaemia, rebound acid secretion
- HCO3-, CO3- → CO2 gas formation resulting in gastric distention, belching
- Mg2+ → osmotic diarrhoea
- Al3+ → constipation
- Avoid long-term use in patients with renal insufficiency
- Affect absorption of other medications → do not take within 2 hours of other medication
Why is Mg2+ and Al3+ combined together in antacids
Mg2+ → osmotic diarrhoea
Al3+ → constipation
Combined formulation minimises impact on bowel function
Examples of H2-receptor antagonist
- Cimetidine
- Ranitidine
- Famotidine
MOA of H2-receptor antagonist
- Competitive inhibitors of H2 receptors on parietal cells
2. Suppress gastric acid secretion and pepsin concentration induced by histamine, gastrin and acetylcholine
Efficacy of H2-receptor antagonist
- Inhibits 60-70% of total 24-hr gastric acid secretion
- Very effective at inhibiting nocturnal acid secretion (due to histamine)
- Modest effect on meal-induced acid secretion (due to gastrin and acetylcholine)
Adverse effects of cimetidine
- Mental confusion in critically ill patients or in renal/hepatic dysfunction
- Anti-androgenic, inhibits estradiol metabolism, increases serum prolactin
• Men: gynaecomastia, impotence
• Women: galactorrhoea - Inhibits cytochrome P450
• Prolongs half-life of other drugs e.g. warfarin, theophylline
Examples of proton-pump inhibitors
- Omeprazole
2. Esomeprazole
MOA of proton-pump inhibitor
- Inactive pro-drugs (absorbed well)
- Enteric-coated formulation (protects activation before absorption)
- 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
Some anti-microbial activity against H. Pylori
Pharmacokinetics of PPIs
- Bioavailability decreased 50% by food → Given on empty stomach (usually before breakfast)
- Inactivate active pumps not quiescent pumps → Must be present during meal time
- Short serum T1/2 = 1-2hr; Tmax = 2-4hr – Given 1hr before meal
- Duration of action 24hr as irreversibly blocks proton pumps → Once daily is sufficient
- Takes 3-4 days to fully inhibit acid secretion
- Efficacy:
– Mean 24hr intra-gastric pH increases to pH 3-4
– Mean number of hours of pH > 4 ranges from 10-14hr
Adverse effects of PPIs
- Can cause headaches, nausea, constipation, flatulence, diarrhoea
- Ca deficiency, risk of osteoporosis, bone fracture: hip, wrist and spine [chronic high dose]
MOA of sucralfate
• 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
Uses of sucralfate
- Limited use for ulcers today as H2 antagonists and PPIs are more effective
- Still used for prevention of stress-related bleeding in critically ill patients
Adverse effects of sucralfate
- Constipation
2. Impairs absorption of other drugs
How should sucralfate be administered
on empty stomach (at least 1hr before meals)
Examples of bismuth compounds
- Bismuth subsalicylate for dyspepsia and acute diarrhoea
2. Bismuth subcitrate potassium for “quadruple therapy” eradication of H. pylori
MOA of bismuth compounds
- Bismuth forms a protective layer protecting ulcers from acid and pepsin
- Stimulates mucus and bicarbonate secretion
- Directly anti-microbial activity against H. pylori
Adverse effects of bismuth compounds
• Although > 99% of bismuth is eliminated in stool <1% is absorbed and stored in many tissues, elimination is by slow renal excretion
• But bismuth compounds generally have a good safety profile when used short-term for ulcers
• Harmless blackening of stool and reversible darkening of tongue
• 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
Indications for misoprostol
Prevention of NSAID-induced peptic ulcers
MOA of misoprostol
- 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
Adverse effects of misoprostol
- Abdominal pain
- Diarrhoea
- Abortion (uterine contraction)
- Bone pain and hyperostosis (excessive bone growth)
