M6: Acid-Peptic Diseases Flashcards
Common Causes of Peptic Ulcer
- Infection:
- Helicobacter pylori (>90%) - Drug-induced:
- NSAIDs
- Steroids
- Antineoplastics - Alcohol
Pharmacotherapy of Peptic Ulcer
- Drugs That Reduce Intragastric Acidity:
- Antacids
- Muscarinic receptor antagonists (anticholinergics)
- Histamine–2 receptor antagonists (H2 blockers)
- Proton pump inhibitors (PPIs) - Drugs that Promote Mucosal Defense:
- Sucralfate
- Prostaglandin analogs
- Bismuth compounds
ANTACIDS
Have been around for centuries
Widely used – OTC
Weak bases (alkaline substance):
- Na, Ca, Al, or Mg salts
Mechanism of action:
Neutralize the gastric acid
- e.g., Acid + Alkali = Neutral Salt
Muscarinic Receptor Antagonists
Compared to other medications:
- Less effective
- More adverse effects
Limited use nowadays
H2 BLOCKERS (-TIDINE)
- Mechanism of Action
- Pharmacokinetics
- Adverse Effects
- Drug Interactions
- Admintertration
DRUGS:
1. Cimetidine
2. Ranitidine
3. Nizatidine
4. Famotidine
MECHANISM OF ACTION:
1. Selectively block H2 receptors on the parietal cells
2. ↓ gastric acidity (+/⎼ 70%) mainly at night
PHARMACOKINETICS:
1. t1/2: 1.1 – 4.0 hours
2. Metabolized by the liver
3. Excreted through the kidney
ADVERSE EFFECTS: <3% is safe
1. Diarrhea, headache, fatigue, myalgias, and constipation
2. Impotence and gynecomastia – cimetidine
DRUG INTERACTIONS:
Cimetidine ↓ hepatic microsomal enzymes (cytochrome P450s) →
↓ other drug metabolism → ↑ drug levels & toxic response
ADMINERSTRATION:
1. Oral
- Twice daily 0.5 h before meals
- IV (limited use)
PROTON PUMP INHIBITORS (-PRAZOLE)
- Mechanism of Action
- Pharmacokinetics
- Adverse Effects
- Administration
- Availiability
DRUGS:
1. Omeprazole
2. Esomeprazole
3. Lansoprazole
4. Dexlansoprazole
5. Pantoprazole
6. Rabeprazole
- Most potent acid suppressors
- Were introduced in the late 80s
- All contain benzimidazole ring
MECHANISM OF ACTION:
1. Irreversible ↓ H+/K+-ATPase proton pump →
2. Prevents acid secretion into the gastric lumen
3. ↓ gastric acidity (>90%)
PHARMACOKINETICS:
1. Absorption:
- Through the intestine
- Delayed by food intake
2. Inactive prodrugs → activated in the parietal cells
3. t1/2: 0.5 – 2.0 hours
ADVERSE EFFECTS: 1-5% → safe
1. Diarrhea – headache – abdominal pain
2. Low gastric acidity →
- Interfere with vitamin B12 absorption
- Bacterial colonization
ADMINERSTRATION:
1. Oral
2. Once a day 1 hour before meal
AVAILIABILTIY:
1. Rx
2. OTC (some)
Pharmacotherapy of Peptic Ulcer
- Drugs that reduce intragastric acidity:
- Antacids
- Muscarinic receptor antagonists (anticholinergics)
- Histamine–2 receptor antagonists (H2 blockers)
- Proton pump inhibitors (PPIs) - Drugs that promote mucosal defense:
- Sucralfate
- Prostaglandin analogs
- Bismuth compounds
SUCRALFATE
- Composition: sucrose + Al(OH)3
- Acts locally in the stomach
- Reacts with gastric HCl → viscous paste-like coat → protects the gastric mucosa
- Minimal absorption (<3%) → no systemic adverse effects
- Administration:
oral – qid – 1 hour before meals - Limited use nowadays
PROSTAGLANDINS ANALOGS – MISOPROSTOL
- Mechanism of Action
- Pharmacokinetics
- Adminestration
PGE1 analog
MECHANISM OF ACTION:
1. ↑ mucus secretion and HCO3 → protects gastric mucosa → ↓ NSAID-induced ulcers
2. ↓ HCl secretion
PHARMACOKINETICS:
1. rapidly absorbed & metabolized
2. short t1/2: <0.5 h
ADMINERSTRATION:
1. oral – qid
BISMUTH COMPOUNDS
2 compounds:
1. bismuth subsalicylate
2. bismuth subcitrate potassium
Frequently used in combinations:
1. with PPIs & antibiotics – treatment of helicobacter pylori
2. with Kaopectate – treatment of dyspepsia & acute diarrhea
Very safe
Causes harmless poop
PEPTIC ULCER & H. PYLORI
Helicobacter Pylori:
1. Gram negative bacilli
2. responsible for >90% of peptic ulcer disease
Treatment:
1. Quadruple therapy: PPI + tetracycline + metronidazole + bismuth
2. Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole)
10-14 days for eradication of the bacteria
