Study guide: Drugs for Peptic Ulcer

📋 Course Outline

1. Peptic Ulcer Causes and Defenses
2. Gastric Acid Secretion
3. Acid-Secretion Inhibitors
4. Antacids and Acid Neutralization
5. Mucosal Protective Agents
6. Antibiotics Against H. pylori
7. H. pylori Treatment Regimens

📖 1. Peptic Ulcer Causes and Defenses

🔑 Key Concepts & Definitions

• Peptic ulcer: A break in the mucosa of the stomach (gastric ulcer) or duodenum (duodenal ulcer).

★ Must-know

📌 A peptic ulcer may occur when aggressive factors exceed defensive factors.

• The aggressive factors are: acid, pepsin, non-steroidal anti-inflammatory drugs (NSAIDs), alcohol, stress, smoking

• The defensive factors are:

  • mucus
  • bicarbonate (HCO3−)
  • blood flow
  • prostaglandins
  • nitric oxide
  • growth factors

Further detail

• Helicobacter pylori can survive in acidic conditions and is associated with peptic ulcer.

• Peptic ulcer treatment can involve: removing risk factors such as alcohol, cigarettes, and stress, decreasing or neutralizing acid, promoting mucosal defense, eradicating H. pylori with antibiotics

💡 Memory Hook

Aggressive factors damage; defensive factors protect.

📖 2. Gastric Acid Secretion

★ Must-know

• Gastrin, histamine, and acetylcholine stimulate gastric acid secretion through receptors and signaling pathways that act on parietal cells and the H+/K+ ATPase proton pump.

Further detail

• The pathway includes:
  • H2 receptors
  • M3 receptors
  • M1 receptors
  • gastrin (CCK) receptors
  • calcium
  • protein kinases
  • cAMP

💡 Memory Hook

Gastrin, histamine, and acetylcholine converge on parietal-cell acid secretion.

📖 3. Acid-Secretion Inhibitors

★ Must-know

• H2 antagonists include:

  • cimetidine
  • ranitidine
  • nizatidine
  • famotidine

• H2 antagonists decrease gastric acid secretion by blocking histamine H2 receptors.

• Cimetidine inhibits hepatic cytochrome P450 enzymes, reducing the metabolism and increasing the blood levels and toxicity risk of drugs such as phenytoin, theophylline, and warfarin.

• Proton pump inhibitors include:

  • omeprazole
  • esomeprazole
  • lansoprazole
  • pantoprazole
  • rabeprazole

• Proton pump inhibitors inhibit the H+/K+ ATPase proton pump and are similar in potency and pharmacokinetics.

Further detail

• H2 antagonists are generally well tolerated but may cause gastrointestinal disturbance, headache, or dizziness.

• Cimetidine inhibits dihydrotestosterone binding to androgen receptors and can cause impotence and gynecomastia in men.

• Muscarinic antagonists include pirenzepine and dicyclomine, but are rarely used because they are less effective than H2 antagonists and proton pump inhibitors and can cause dry mouth, blurred vision, cardiac arrhythmias, and urinary retention.

• Proton pump inhibitors are generally well tolerated but may cause headache, dizziness, and gastrointestinal disturbance.

📖 4. Antacids and Acid Neutralization

★ Must-know

• Antacids include:
  • sodium bicarbonate
  • calcium carbonate
  • magnesium hydroxide
  • aluminium hydroxide

Further detail

• Antacids neutralize gastric acid to provide quick relief, but pain may return after 1–2 hours.

• Sodium bicarbonate can cause belching through gas production and can exacerbate fluid retention in patients with heart failure, hypertension, or renal insufficiency because of its sodium content.

• Calcium carbonate can cause belching, hypercalcaemia, renal calculi, and constipation.

• Magnesium hydroxide can cause diarrhoea, whereas aluminium hydroxide can cause constipation, so they are commonly administered together in proprietary formulations.

📖 5. Mucosal Protective Agents

🔑 Key Concepts & Definitions

• Sucralfate: A complex of sucrose sulphate and aluminium hydroxide that forms a protective gel over gastric epithelial surfaces, including ulcerated areas.
• Misoprostol: A prostaglandin analogue.

★ Must-know

• 🔄 In acid, sucralfate: releases aluminium, the aluminium gains a strong negative charge, the aluminium binds positively charged groups in mucus glycoproteins, a viscous gel forms and adheres to gastric epithelial cells, the gel protects the surface from acid and pepsin

• Bismuth combines with mucus glycoproteins to form a barrier that protects ulcerated areas from acid and pepsin.

• Bismuth stimulates secretion of:

  • mucus
  • bicarbonate
  • prostaglandins

• Prostaglandins:

  • decrease acid secretion
  • increase mucus secretion
  • increase bicarbonate secretion
  • increase gastric blood flow

📌 Misoprostol should not be used during pregnancy because it stimulates uterine contraction.

Further detail

• Sucralfate is not absorbed and is virtually devoid of systemic adverse effects, but constipation occurs in 2% of patients due to its aluminium salt.

📌 Antacids given concurrently with or before sucralfate reduce its efficacy because sucralfate requires an acidic environment for activation.

• Sucralfate may bind:

  • quinolone antibiotics
  • phenytoin
  • warfarin
  • food

• Bismuth can darken the teeth, tongue, and stool, with stool darkening potentially confused with gastrointestinal bleeding.

📌 Prolonged bismuth use in patients with renal failure may cause toxicity resulting in encephalopathy, ataxia, headache, confusion, or seizures.

📌 Bismuth should be taken on an empty stomach because it may bind to food and lose efficacy.

• Misoprostol can cause gastrointestinal discomfort, including diarrhoea and abdominal cramps.

📖 6. Antibiotics Against H. pylori

★ Must-know

• Antibiotics used to eradicate H. pylori include:
  • amoxicillin
  • clarithromycin
  • tetracycline
  • metronidazole

• Amoxicillin inhibits transpeptidase and thereby interferes with bacterial cell-wall synthesis.

• Clarithromycin binds to the 50S ribosomal subunit and inhibits translocation during protein synthesis.

• Tetracycline binds to the 30S ribosomal subunit and blocks tRNA attachment to the ribosomal A site.

• 🔄 Metronidazole acts through:
  1. PFOR chemically reduces its nitro group
  2. the product disrupts DNA helical structure
  3. DNA synthesis is inhibited

Further detail

• Amoxicillin can cause hypersensitivity reactions, including rash, fever, and anaphylactic shock, and gastrointestinal disturbance such as diarrhoea due to alteration of gut bacterial flora.

• Tetracycline can cause: nausea, vomiting, tooth discolouration, enamel dysplasia, photosensitivity, reduced bone growth in children younger than 8 years

• Metronidazole is selectively toxic to anaerobic organisms, including H. pylori, because PFOR is expressed in anaerobic organisms but not in mammalian systems.

• Metronidazole can cause gastrointestinal disturbance, metallic taste, and occasional sensory neuropathy.

📖 7. H. pylori Treatment Regimens

📝 Essential Points

• Triple therapy for H. pylori-associated peptic ulcer combines a proton pump inhibitor with two of clarithromycin, amoxicillin, and metronidazole.

• Quadruple therapy combines:

  • a proton pump inhibitor
  • bismuth
  • metronidazole
  • tetracycline