Pharmacology of Proton-Pump Inhibitors

Stress-related Gastritis

• Act as prophylaxis for recurrent ulcers in patients at risk
• Can be treated with proton-pump inhibitors (PPIs) such as omeprazole, which reduces both meal-stimulated and basal acid secretion

Proton-pump Inhibitors (PPIs)

• Irreversible inhibitors of the H+/K+-ATPase proton pump in parietal cells
• Block the transport of acid from the cell into the lumen
• Indications: gastroesophageal reflux disease (GERD), peptic ulcer disease, nonulcer dyspepsia, stress-induced gastritis, and gastrin-secreting tumors (Zollinger-Ellison syndrome)
• Adverse effects: headaches, gastrointestinal disturbances, and reduction in acid production may permit bacterial overgrowth
• Major drug interactions: inhibit the metabolism of other drugs like warfarin, can result in drug toxicity

Prostaglandins

• Misoprostol (Cytotec) is a methyl analog of PGE1 that acts on parietal cells to inhibit acid secretion and stimulate bicarbonate and mucus production
• Increases uterine contractions
• Clinical uses: prevention of NSAIDs-induced ulcer, termination of pregnancy, and induction of labor (off-label)
• Side effects: diarrhea, abortion, premature birth, birth defects, and uterine rupture (life-threatening)

Protective Agents

• Sucralfate (Carafate) is a polysaccharide complexed with aluminum hydroxide that protects ulcerated areas from further damage and promotes healing
• Effects: stimulates mucosal production of prostaglandins, inhibits pepsin, and has side effects of constipation and nausea
• Used in critical care settings for stress-related gastritis

Antacids

• Weak bases taken orally to partially neutralize gastric acid and reduce pepsin activity
• Reduce the pain associated with ulcers and may promote healing
• Prototype agents: sodium bicarbonate, calcium carbonate (TUMS, Os-Cal)

Other Agents

• Histamine1 (H1)-receptor antagonists: doxylamine + Vit B6, meclizine, and promethazine, used to treat motion sickness and morning sickness
• Dopamine antagonists: metoclopramide, used to treat nausea and vomiting, with side effects of sedation, diarrhea, and motor dysfunction
• 5-HT3 antagonists: ondansetron, used to treat nausea and vomiting, with side effects of mild constipation
• Benzodiazepines: lorazepam, diazepam, used as anxiolytic agents to reduce anticipatory emesis

Agents Used to Treat Diarrhea

• Opiates and opioid-containing preparations: act directly on opiate µ-receptors to decrease GI motility and increase transit time
• Diphenoxylate: a synthetic morphine analogue used to treat diarrhea
• Loperamide: an opioid agonist with no CNS activity, used to treat diarrhea, with a potential for severe constipation
• Bulk-forming laxatives: psyllium and methylcellulose, used to treat constipation
• Osmotic agents: magnesium citrate, magnesium sulfate, magnesium hydroxide, and sodium phosphates, used to treat constipation
• Lubricant laxatives: mineral oil and glycerin, used to treat constipation, with limitations of decreasing absorption of fat-soluble vitamins

Learn about the mechanisms of proton-pump inhibitors, such as omeprazole, in preventing stress-related gastritis and recurrent ulcers. Understand how they work to block acid transport in parietal cells.