Anti-Peptic Disease Drugs

Question 1

H2 Receptor Antagonsists

Answer 1

“-tidines”
- Cimetidine (tagamet)
- Ranitidine (zantac)
- Famotidine (pepcid)
- Nizatidine ( axid)
- Competitive, selective inhibitors of parietal cell H2 receptors
- Suppress basal and meal stimulated acid secretion in a linear dose dependent manner; most pronounce effects on nocturnal acid secretion
- Inhibit 60-70% of 24 hr total acid secretion when given BID at prescribed doses ; OTC preps
GERD: Intermittent dosing for infrequent sx, prophylactically or BID for frequent heartburn
PUD: 1x daily dosing at night causes >80-90% ulcer healing after 6-8 weeks of treatment
Adverse Effects: - Diarrhea, headache, fatigue, myalgias, constipation (3%)
- Contraindicated in pregnancy (crosses placenta) and in nursing mothers (secreted in breast milk)
- Cimetidine slows hepatic metabolism of drugs and Ranitidine does too to a lesser extent.

Question 2

PPIs

Answer 2

“-Prazoles”
- Omeprazole (Priolsec), Esomeprazole (Nexium), Lansoprazole (Prevacid), Dexlansoprazole, Pantoprazole (Protonix), Rabeprazole
- Pro-Drugs– get activated via. protonation in the acid environment of the secretory canaliculi of parietal cells – activated drug forms a covalent bond w/ H+/K+ ATPase on parietal cells which irreversibly inactivates the proton pump
- Markedly suppresses both fasting and meal stimulated acid secretion
- Inhibits 90-98% of 24 hr acid secretion; Admin 1x daily on empty stomach (food decreases bioavailability by 50%) 1 hr before meal for peak effectiveness
- T1/2 = 0.5-2 hrs– acid inhibition lasts up to 24 hrs b/c of irreversible PP activation
- GERD: PPIs = first line tx, 1 x daily dos
- PUD: >90% healing of duodenal ulcers in 4 weeks and gastric ulcers in 6-8 weeks
Adverse Effects: - Diarrhea, headache, abdominal pain (1-5%)
- Increase risk of enteric infections (by suppressing gastric acid barrier)
- Increased risk of C. Diff in Hospitalized pt.
- May cross BBB and increase amyloid production/degradation and may decrease absorption of B12 and other nutrients (some evidence)

Question 3

Antacids

Answer 3

• Weak bases that neutralize gastric HCl on contact to form a salt and water
• Lower gastric and peptic activity (peptic is inactive at pH > 4)
• Mg(OH)2, Al(OH)3
• Intermittent heartburn treatment
• Promotes healing of duodenal ulcers but no evidence for gastric ulcers
• Antacids + Alginic Acid (mucosal protective agent) decrease GERD sx but don’t tx natural history of disease

Question 4

Sucralfate

Answer 4

• Sucrose octasulfate + Al(OH)3
• Viscous substance, water insoluble, weak buffer
• Selectively binds necrotic ulcer tissue and acts as a barrier to acid, pepsin and bile
• May stimulate PGs which in turn stimulate secretion of mucous and HCO3
• Prevents duodenal ulcers, less w/ gastric
• Requires acidic conditions for activation- should not be taken w/ H2 blockers or PPIs

Question 5

Colloidal Bismuth Compunds

Answer 5

• Bismuth Subsalicylate (Pepto Bismol)
• Bismuth subcitrate potassium
• Selectively bind ulcer, coat it and protect it from acid and pepsin
• Direct anti-microbial effects against H.Pylori and bind enterotoxins
• 98% healing of H. Pylori ulcers when combo w/ tetracycline + metronidazole
  Pylera: Bismuth subcitrate + tetracycline + metronidazole

Question 6

Misopristol

Answer 6

• Methyl analog of PGE1– stimulates mucous and HCO3 secretion and increases mucosal blood flow
• Decreases histamine stimulated cAMP production – modest acid inhibition
• Approved for prevention of NSAID induced ulcers
  Adverse effects: - Dose dependent diarrhea
• Stimulatory effects on uterus- contraindicated if possibly pregnant