OIA2004 PHARMACOLOGY OF PUD

What is PUD?

Mucosal erosion due to imbalance between aggressive factors (acid, pepsin, bile) and defensive factors (mucus, bicarbonate, PGs, blood flow).

Main Causes of PUD

H. pylori infection

NSAID use

Goals of PUD Therapy

Eradicate H. pylori

Reduce intragastric acidity

Promote mucosal protection

Quadruple Therapy

Bismuth subsalicylate + Metronidazole + Tetracycline + PPI

Triple Therapy

Amoxicillin (or Metronidazole) + Clarithromycin + PPI

Preferred if no macrolide resistance

Examples of PPIs

Omeprazole, Lansoprazole, Pantoprazole

MOA of PPIs

Irreversibly inhibit H⁺/K⁺-ATPase (proton pump) in parietal cells.

Pharmacokinetics of PPIs

Prodrugs, activated in parietal cells

Covalent bonding → long duration, despite short half-life

Dosing Instructions of PPI

Take 30–60 minutes before meals for best efficacy.

Clinical Uses of PPIs

GERD, PUD, Zollinger-Ellison syndrome, NSAID-induced ulcers

Adverse Effects of PPIs

C. difficile infection, diarrhea

Long-term: ↓ B12, ↑ fracture risk

Drug Interactions (PPIs)

Inhibit CYP2C19 → ↓ clopidogrel activation

↓ CaCO₃ absorption → use calcium citrate

Examples of H2RAs

Cimetidine, Ranitidine, Famotidine, Nizatidine

MOA of H2RAs

Competitively block H2 receptors on parietal cells

↓ acid secretion (basal, food-stimulated, nocturnal)

Uses of H2RAs

PUD, acute stress ulcers, GERD

Not preferred for NSAID-induced ulcers

Adverse Effects (H2RAs)

Diarrhea, headache

Cimetidine: gynecomastia, galactorrhea (anti-androgen effects)

Drug Interactions (Cimetidine)

Inhibits CYP450, affects warfarin, phenytoin, theophylline

Limitations of H2RAs

Tolerance develops, especially with chronic use

MOA of Antacids

Neutralize gastric acid → form salt + water

Timing for Use (Antacids)

Take after meals for best effect

Onset & Duration (Antacids)

Rapid relief, but short duration

Examples of Antacids

Aluminum hydroxide, Magnesium hydroxide, Calcium carbonate

Adverse Effects (Antacids)

May impair absorption of other drugs

Timing caution: 1 hr before or 2 hrs after other meds

PG analog

Example: Misoprostol

MOA (Misoprostol)

↓ acid secretion, ↑ mucus & bicarbonate production

Use Case (PG analogs)

Prevent NSAID-induced ulcers in high-risk patients

Adverse Effects (Misoprostol)

Diarrhea, abdominal cramps

CI in pregnancy (stimulates uterine contraction)

Sucralfate

Forms a protective gel over ulcers

Binds to ulcer base, protecting from pepsin/acid

Sucralfate Limitations

Requires multiple doses, drug binding interactions

Bismuth Subsalicylate

Quadruple therapy component for H. pylori

MOA (Bismuth)

Antimicrobial, coats ulcers, inhibits pepsin

CYP2C19 Inhibition (Omeprazole)

↓ conversion of clopidogrel to active form → ↓ efficacy

Effect of Increased Gastric pH

↓ absorption of some drugs (e.g., ketoconazole)

CYP Inhibitors vs. Inducers

Inhibitors: ↓ metabolism → ↑ drug levels

Inducers: ↑ metabolism → ↓ drug levels

PPI + Clopidogrel

Avoid omeprazole, consider pantoprazole if PPI needed

PPI Counseling

Long-term use → check calcium, B12, Mg

Report prolonged diarrhea

H2RA Timing

Take at bedtime for best suppression of nocturnal acid

Pregnancy Consideration

Avoid Misoprostol, use H2RAs or antacids

Preferred Agents for NSAID Ulcer Prevention

PPI > Misoprostol (better tolerated)

PUD + H. pylori Strategy

Always use antibiotics + PPI; monotherapy ineffective