Gastric & Peptic ulcer Flashcards
List THREE classes of agents that reduce gastric acidity.
Antacids
H2‐receptor Antihistamines
Proton Pump Inhibitors (PPI)
List THREE examples of mucosal protective agents
- Sucralfate
- Misoprostol
- Bismuth Compounds
Rank common antacids according to their rate of neutralization.
NaHCO3> CaCO3> Mg(OH)2> Al(OH)3
Why is simethicone often found in antacid formulations?
Antifoaming activity coalesces bubbles and reduces bloating.
Helps to reduce gastric distention, belching discomfort side effects.
Why are magnesium and aluminium compounds usually formulated together in antacids?
Magnesium causes osmotic diarrhoea
Aluminum causes constipation
Together the effects balance
List adverse effects of antacids.
- 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
Name an example of an H2 antihistamine
Cimetidine, ranitidine, famotidine
When is the best time to take H2 antihistamines?
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.
List adverse effects of H2 antihistamines.
Common: constipation, headaches
Uncommon: agitation
List adverse effects of cimetidine.
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
Name ONE example of a proton-pump inhibitor
Omeprazole, esomeprazole, and other *prazole
Briefly describe the mechanisms of action of PPIs that result in selective proton pump inhibition in the parietal cell canaliculi
- 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
Briefly describe the duration of action of omeprazole.
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
When is the best time to take PPIs?
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)
List adverse effects of omeprazole.
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
Briefly describe the properties and mechanisms of action 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
Briefly describe the clinical use and adverse effects of sucralfate
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
Briefly describe the mechanisms of action of bismuth compounds as mucosal protective agents.
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
Briefly describe the 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
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
Why is use of misoprostol limited?
Limited use today due to:
Adverse effects
Multiple daily dosing (non-compliance)
Advent of COX-2 selective NSAIDs
Potential for abuse as an abortifacient
List adverse effects of misoprostol.
Adverse Effects:
Abdominal pain/cramps
Diarrhoea
Abortion (uterine contraction)
Bone pain and hyperostosis (excessive bone growth)
Explain the properties and mechanisms of action of misoprostol
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
What is triple therapy?
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)
What is the role of PPI in triple therapy?
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
What is quadruple therapy?
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)
List adverse effects of triple therapy
Common side effects are diarrhoea, nausea and vomiting
