6.2 Gastrointestinal Pharmacology

Acid-Suppressing Therapy

Proton Pump Inhibitors

Proton pump inhibitors (PPIs) - omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole - irreversibly inhibit the H+/K+-ATPase (proton pump) on the parietal cell, the final common pathway of gastric acid secretion. Because they bind actively secreting pumps, they work best taken 30-60 minutes before the first meal of the day. Acid suppression takes 1-3 days to reach full effect since new pumps must be synthesised.

Long-term PPI use carries risks the exam expects you to counsel on: hypomagnesemia (impaired intestinal absorption, occasionally with hypocalcemia and tetany), reduced vitamin B12 and iron absorption, increased Clostridioides difficile and enteric infections, community-acquired pneumonia, and hip and vertebral fractures with chronic high-dose use. Use the lowest effective dose and review the indication regularly.

The most tested interaction: omeprazole (and esomeprazole) inhibit CYP2C19, the enzyme that converts the prodrug clopidogrel into its active antiplatelet metabolite, reducing its effect and raising cardiovascular event risk. When a PPI is needed with clopidogrel, choose pantoprazole (or lansoprazole), which inhibits CYP2C19 far less.

H2 Receptor Antagonists, Antacids and Sucralfate

H2 receptor antagonists (famotidine; ranitidine was withdrawn worldwide because of N-nitrosodimethylamine contamination) competitively block histamine H2 receptors on parietal cells. They are weaker than PPIs, useful for mild reflux and nocturnal acid breakthrough, but tolerance (tachyphylaxis) develops with continuous use. Antacids (aluminium, magnesium, calcium salts) neutralise existing acid for rapid short-lived relief; magnesium salts cause diarrhea, aluminium and calcium cause constipation. The key safety point is chelation: divalent and trivalent cations bind tetracyclines, fluoroquinolones, oral iron, bisphosphonates and levothyroxine, markedly reducing their absorption - separate doses by at least 2-4 hours. Sucralfate forms a protective barrier over ulcer bases in the presence of acid, so give it on an empty stomach and away from other drugs, which it can adsorb.

Helicobacter pylori Eradication

Standard triple therapy combines a PPI with clarithromycin plus amoxicillin (substitute metronidazole in penicillin allergy) for 14 days. Where clarithromycin resistance is high, bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole) is preferred. Confirm eradication with a urea breath test or stool antigen test at least 4 weeks after antibiotics finish, and stop the PPI 2 weeks before testing to avoid false negatives.

Antiemetics

Laxatives: Match the Class to the Patient

• Bulk-forming (ispaghula/psyllium, methylcellulose): first-line for chronic constipation; must be taken with adequate fluid and avoided in suspected obstruction or faecal impaction.
• Osmotic (macrogol/polyethylene glycol, lactulose): draw water into the lumen; macrogol is first-line for chronic constipation and faecal loading, while lactulose is also used in hepatic encephalopathy to trap ammonium. Onset is 1-3 days.
• Stimulant (senna, bisacodyl): increase peristalsis; reserve for short-term or opioid-induced constipation; overuse causes cramping and, historically, concern for cathartic colon.
• Stool softeners (docusate): weak evidence; not recommended as sole therapy.

Antidiarrheals and Oral Rehydration

Loperamide, a peripheral opioid-receptor agonist, slows gut motility for symptomatic relief of acute non-bloody diarrhea. It must be avoided in bloody diarrhea, high fever or suspected invasive bacterial colitis (including C. difficile), where delaying clearance of pathogens can precipitate toxic megacolon. The true mainstay of diarrhea management is fluid replacement: oral rehydration solution (ORS) exploits glucose-driven sodium co-transport in the small intestine - glucose absorption carries sodium and water with it, which is why ORS contains both glucose and electrolytes in defined proportions.

Inflammatory Bowel Disease and Gallstones

5-Aminosalicylates (5-ASAs) such as mesalazine are first-line for inducing and maintaining remission in mild-to-moderate ulcerative colitis, acting topically on the colonic mucosa; sulphasalazine's sulphapyridine moiety drives many of its side effects. For steroid-dependent or refractory disease, thiopurines (azathioprine, mercaptopurine) are used - check thiopurine methyltransferase (TPMT) status first because low TPMT activity causes severe myelosuppression, and monitor full blood counts regularly. Allopurinol dangerously raises thiopurine levels. Ursodeoxycholic acid is a hydrophilic bile acid that dissolves small cholesterol gallstones in patients unfit for surgery and slows disease progression in primary biliary cholangitis.

Dyspepsia Triage and NSAID Ulcer Prophylaxis

Community pharmacists are expected to distinguish simple dyspepsia from cases needing referral. Alarm features that mandate medical review include unintended weight loss, progressive dysphagia, persistent vomiting, gastrointestinal bleeding or iron-deficiency anemia, an abdominal mass, and new-onset symptoms in older patients. Without alarm features, short courses of antacids, an H2 blocker or a PPI trial are reasonable, with H. pylori test-and-treat considered for persistent symptoms. Patients who must continue NSAIDs and carry ulcer risk factors (age over 65, previous ulcer or bleed, concurrent corticosteroids, aspirin or anticoagulants) should receive gastroprotection with a PPI; misoprostol, a prostaglandin E1 analogue, is the alternative but is limited by diarrhea and cramping and is absolutely contraindicated in pregnancy because of its uterotonic effect. Choosing the antiemetic by cause follows the same logic: 5-HT3 antagonists for chemotherapy and postoperative nausea, dopamine antagonists for drug-induced and gastroenteritic nausea, and antimuscarinics or sedating antihistamines such as cyclizine for motion sickness and vestibular causes.