Peptic Ulcer Disease (PUD)

Question 1

Describe H pylori? Is eradication important?

Answer 1

H pylori: GN microerophillic S-shaped rod w flagella
• Virulence factors:
1 ) Urease: enzyme breaks down urea to ammonia -> increase pH -> allows bacteria to survive in gastric acid
2) Phospholipase: breaks down gastric mucus
3) Adhesins: helps stick to gastric wall
4) Flagella: allows motility on mucosal surface

Question 2

Why is H pylori eradication important in PUD?

Answer 2

PUD pathogenesis: mucosal and humoral response to bacteria causes ulceration
• Host inflammatory response: neutrophils, lymphocytes and macrophages
• Mucosal and humoral responses do not eradicate bacteria
• Neutrophils -> proteases -> mucosal breakdown -> ulceration and impaired healing

Eradication benefits: causes 70% peptic ulcers
• Promotes healing by removing causative organism and inflammatory instigator
• Prevent complications (chronic ulcer)- gastric adenocarcinoma, MALT lymphoma, duodenal ulcer

Question 3

Describe the 1st line therapy for PUD?

Answer 3

First line: Triple therapy for 7 days (85% success)

1) Clarithromycin
2) Amoxicilin
3) PPI (e.g. esomeprazole)

Question 4

Describe the 2nd line therapy for PUD?

Answer 4

Second line: Quadruple therapy 7-14 days (85% success)

• Indication: failure due to Abx resistance
  1) Bismuth Subsalicylate (antacid)
  2) Metronidazole
  3) Tetracycline (e.g. Doxycycline)
  4) PPI (e.g. esomeprazole)

Question 5

Describe the MA and SE of Clarithromycin?

Answer 5

Clarithromycin (500mg PO BD)
o Class: Macrolide
o MA: binds to 50S and 70S ribosomal subunit -> inhibits protein synthesis
o SE: N/V, diarrhoea, abdo pain, candidiasis
o Interactions: CYP inducers or inhibitors (Warfarin, NSAID)

Question 6

Describe the MA and SE of Amoxicilin?

Answer 6

Amoxicilin (1g PO BD)
o Class: broad spectrum penicillin
o MA: binds to penicillin binding protein (PBP) -> inhibits transpeptidation -> inhibits cross-linking -> inhibits cell wall biosynthesis -> cell lysis -> bactericidal
o SE: moderate transaminase rise, rash
o Interactions: anticoags, allopurinol, certain Abx
o If penicillin allergy, swap for Metronidazole (400mg PO BD)

Question 7

Describe the MA and SE of Esomeprazole?

Answer 7

PPI (e.g. Esomeprazole, 20mg PO BD)
o MA: converted to active form at secretory canaliculi of parietal cell -> inhibits H+/K+/ATPase pump -> decreased gastric acid secretion
o Max effect 5 days
o SE: gastric polyps (chronic use), headache, nausea, diarrhoea, parasthesia, rash, confusion

Question 8

Describe the MA and SE of Bismuth Subsalicylate?

Answer 8

Bismuth Subsalicylate (antacid)
o MA: interfer w bacterial cell membrane, protein and cell wall synthesis
o SE: harmless/reversible tongue and stool darkening (formation of bismuth sulfite)

Question 9

Describe the MA and SE of Metronidazole?

Answer 9

Metronidazole
o Class: 5-nitoimadazoles
o MA: inhibits nucleic acid synthesis and replication
o Spectrum:
- Bacteria- most anaerobic bacteria ( e.g. C diff)
- Protozoa- Giardia, trichomonas, entamoeba
o SE: N/V, leukopenia, neutropenia, peripheral neuropathy, CNS toxicity, metallic taste
o Interaction: Disulfram

Question 10

Describe the MA and SE of Tetracyline?

Answer 10

Tetracyline (e.g. Doxycycline)
o MA: bacteriostatic: reversibly binds 30S ribosomal subunit -> inhibits bacterial translation -> inhibits protein synthesis
o Spectrum: broad spectrum for GP and GN, good for atypicals
o SE: chelates Ca in teeth and bone (enamel dysplasia, decerased bone growth), GI discomfort, candidiasis, allergy, N/V
o Elimination: faecal, thus can be used in renal impairment
o CI: pregnancy, children <8yo