Medical Pharmacology: Peptic Ulcer Disease

Medical Pharmacology Chapter 27: Gastrointestinal Drugs

Gastric Physiology

Physiological stimulants of gastric acid secretion
- Major physiologic stimulus: food intake involves three phases:
  1. Cephalic phase
    - Gastric acid secretion responds to anticipation of food, sight, smell, taste
  2. Gastric phase
    - Stimulation of mechanical and chemical gastric wall receptors by luminal contents.
  3. Intestinal phase
    - Gastrin release (small amount); release of other peptides that stimulate gastric acid secretion
- Food constituents:
  - Coffee (both caffeine containing and caffeine free) stimulates gastric acid secretion by stimulating gastric release
  - Beer and wine: stimulation of gastric acid secretion
Physiologic inhibition and gastric acid release
- Factors that inhibit gastric acid secretion include:
  - Hyperglycemia
  - Hypertonic fluids
  - Duodenal fat
  - Duodenal acid
  - Intragastric pH = 3; partial inhibition
  - Intragastric pH < or = 1.5; complete blockade of gastrin release
- Somatostatin effects:
  - Antral mucosal endocrine cells (D cells) contain somatostatin and impinge on nearby gastrin cells and parietal cells.
  - Somatostatin reduces gastrin release thereby reducing gastric acid secretion by:
    1. Inhibiting parietal cells secretion
    2. Inhibiting histamine release by enterochromaffin-like cells
Role of pepsin in peptic ulcer disease
- Secreted gastric acid plus effects of pepsin promote tissue injury
- Gastric acid promotes cleavage of pepsinogen (inactive) to proteolytically-active pepsins
- Pepsinogen classification:
  - Direct correlation between pepsinogen I serum concentrations and maximal gastric acid secretion.

Friedman, L. S. and Peterson, W.L. Peptic Ulcer and Related Disorders In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1597-1616.

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