Anti-ulcer Agents Flashcards
What are the main groups of anti-ulcer drugs?
- Antacids
- H2 RA/ H2-Blockers
- Proton-pump inhibitors (PPI)
- Sucralfate
- Misoprostol
- Bismuth compounds
- Clarithromycin + Amoxicillin/Metronidazole
What are the agents that reduce gastric acidity?
- Antacids
~ Sodium bicarbonate
~ Calcium carbonate
~ Magnesium hydroxide
~ Aluminium hydroxide - H2 RA
~ Famotidine
~(Ranitidine, Cimetidine) - PPI
~ Omeprazole
~ (Esomeprazole)
What are the mucosal protective agents?
- Coat ulcer pits
~ Sucralfate
~ Bismuth compounds - Prostalglandin analogue
~ Misoprostol
What drugs kill H. Pylori?
- Triple therapy
~ Clarithromycin + Amoxicillin
~ PPI
What are the factors contributing to peptic ulcers?
Aggressive factors:
- H. Pylori (damages mucus layer)
- NSAIDS (blocks production of prostalglandins)
- Acid
- Pepsin
- Smoking
Defensive factors:
- Mucus (protects stomach walls)
- Bicarbonate (buffers acidity)
- Blood flow (delivers nutrients for rapid repair and cell turnover in stomach walls)
- Prostalglandins
How is acid released in the stomach?
- Histamine activation of H2 receptors activates proton pumps to release hydrogen ions
- Tf blocking H2 receptors can help to reduce stomach acidity
What is the MOA of antacids?
- Weak bases
- Reduces gastric acidity by neutralising it to form salt and water
- Non-prescription remedy for mild excess acidity, heartburn and dyspepsia
- Rate of neutralisation (most potent)
~ Na > Ca > Mg > Al - Liquid antacids are better than tablets (better rate of dissolution)
- Large and frequent doses are often required (better for temporary release of symptoms but not for severe conditions)
- Some preparations contain simethicone
~ Anti-foaming agent (eases release of gas bubbles via burping or flatulence)
What are the adverse effects of antacids?
Metabolic alkalosis
- Na+: Fluid retention, Hypertension, CHF
- Ca2+: Hypercalcemia, rebound acid secretion
- HCO3- and CO3-: Burping, flatulence
- Mg2+: Osmotic diarrhea
- Al2+: Constipation
- Cannot be taken within 2 hours of other medications
- Avoid long-term use in px with renal insufficiency
What is the MOA of H2 RA?
- Competitive inhibitors of H2 receptors on parietal cells
- Suppresses acid secretion by parietal cells
- Effective at inhibitive nocturnal acid secretion due to histamine
- Modest effect on meal-induced acid secretion due to gastrin and acetylcholine
- Famotidine is the most potent
What are the adverse effects of H2 RA?
- Relatively safe with high therapeutic index
- (F, R) Headache, nausea, dry mouth
- Tachycardia, blood dyscrasia, blurred vision, MSK pain
- (C) Headache, diarrhoea, constipation, fatigue
- Mental confusion in critically ill patients or renal/hepatic px
- Anti-androgenic, inhibits estradiol metabolism and increases serum prolactin
~ Gynecomastia, impotence
~ Galactorrhoea
What is the MOA of PPIs?
- Most potent gastric acid secretion inhibitor
- Irreversibly inhibits active H+-K+-ATPase proton pumps in parietal cells
- Some weak anti-microbial activity against H. Pylori
- Enteric-coated formulation protects against activation by stomach acidity before absorption
- Inactive pro-drugs (so they are absorbed well in intestines)
- Active form is not absorbed well
-Given on an empty stomach, 1 hr before meals (so that drug is most potent when proton pumps are most active after a meal)
- 1x / day
- Takes 3-4 days to fully inhibit acid secretion
What are the adverse effects of PPI?
- Headaches, nausea, flatulence, diarrhoea, dizziness, rash
- May have ^ risk of C.diff or MDRO infections
- Rare but acute interstitial nephritis, CKD and SLE
What is the MOA of sucralfate?
- Negatively charged sucrose sulphate binds to positively-charged proteins
~ Forms a viscous, tenacious gel at the ulcer crater
~ Prevents further acid attack
~ Stimulates mucosal prostalglandin to trigger bicarbonate and mucus secretion - Administered on an empty stomach (at least 1 hr before meals)
What are the adverse effects of sucralfate?
- Constipation
- Impairs absorption of other drugs
What is the MOA of Bismuth compounds?
- Forms a protective layer to protect ulcers from acid and pepsin
- Stimulates mucus and bicarbonate secretion
- Directly anti-microbial activity against H. Pylori
