6.7 Gastrointestinal and Hepatic Pharmacotherapy
Key Takeaways
- Alarm features in dyspepsia — dysphagia, unintended weight loss, gastrointestinal bleeding, persistent vomiting, anemia, or new onset after age 50 — require medical referral rather than a non-prescription trial.
- Helicobacter pylori is treated in Canada with a 14-day quadruple regimen; clarithromycin-based triple therapy is no longer reliable because of resistance rates above 15%.
- Long-term proton pump inhibitor therapy without a documented ongoing indication is a leading deprescribing target, and abrupt discontinuation causes rebound acid hypersecretion that mimics relapse.
- Spontaneous bacterial peritonitis is diagnosed on ascitic fluid with 250 or more polymorphonuclear cells per cubic millimetre and is treated with a third-generation cephalosporin plus albumin.
- Lactulose is titrated in hepatic encephalopathy to produce two or three soft stools per day, with rifaximin added for recurrent episodes.
6.7 Gastrointestinal and Hepatic Pharmacotherapy
Exam Focus: Gastrointestinal complaints reach pharmacists more often than almost any other therapeutic area, so the Evaluating Examination pairs them with triage judgement: recognise the alarm feature, choose the guideline-consistent regimen, and know when the safest recommendation is to stop a drug.
Acid-Related Disorders
Gastroesophageal reflux disease
GERD is retrograde movement of gastric contents causing troublesome symptoms or mucosal injury. Typical presentations are heartburn and regurgitation; atypical ones include chronic cough, hoarseness, and non-cardiac chest pain.
Stepwise therapy:
- Non-pharmacological: weight loss where relevant, elevate the head of the bed, avoid eating within three hours of lying down, and identify individual triggers rather than imposing a blanket exclusion diet.
- Antacids or alginate for infrequent, predictable symptoms.
- Histamine-2 receptor antagonist (famotidine) for mild intermittent symptoms; tachyphylaxis develops within about two weeks of scheduled use.
- Proton pump inhibitor (PPI) once daily 30 to 60 minutes before the first meal for frequent or erosive disease.
Alarm features requiring referral
Do not sell a non-prescription acid suppressant to a patient with dysphagia, odynophagia, unintended weight loss, hematemesis, melena, persistent vomiting, iron-deficiency anemia, a palpable mass, or new-onset dyspepsia after age 50. Each raises the probability of malignancy, stricture, or ulcer bleeding.
Peptic ulcer disease and Helicobacter pylori
The two dominant causes are H. pylori infection and non-steroidal anti-inflammatory drug (NSAID) use. Because Canadian clarithromycin resistance now exceeds the 15% threshold at which triple therapy fails, first-line eradication is a 14-day quadruple regimen:
| Regimen | Components | Duration |
|---|---|---|
| Bismuth quadruple | PPI + bismuth subsalicylate + metronidazole + tetracycline | 14 days |
| Concomitant non-bismuth quadruple | PPI + amoxicillin + metronidazole + clarithromycin | 14 days |
Counsel that bismuth blackens the tongue and stool (harmless, and distinguishable from melena by the absence of other bleeding signs) and that metronidazole with alcohol can produce a disulfiram-like reaction. Confirm eradication with a urea breath test or stool antigen test at least four weeks after antibiotics and at least two weeks after stopping the PPI, because earlier testing gives false negatives.
Deprescribing proton pump inhibitors
PPIs continued without a documented indication are associated with Clostridioides difficile infection, community-acquired pneumonia, hypomagnesemia, vitamin B12 malabsorption, and fracture. Indications justifying continuation include Barrett esophagus, severe erosive esophagitis, chronic NSAID use with risk factors, and Zollinger-Ellison syndrome. Otherwise, taper the dose or move to on-demand use, and warn the patient about rebound acid hypersecretion in the first two weeks so that transient heartburn is not misread as disease relapse.
Inflammatory Bowel Disease
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Distribution | Mouth to anus, skip lesions | Continuous, rectum proximally |
| Depth | Transmural | Mucosal and submucosal |
| Classic complications | Fistulae, strictures, abscess | Toxic megacolon, colorectal cancer |
| Smoking | Worsens disease | Paradoxically associated with lower risk |
| 5-Aminosalicylate role | Limited | Cornerstone of mild to moderate disease |
Therapy escalates from 5-aminosalicylates (ulcerative colitis) through corticosteroids for induction only, to immunomodulators (azathioprine, methotrexate) and biologics (infliximab, adalimumab, vedolizumab, ustekinumab). Before any anti-tumour necrosis factor agent, screen for latent tuberculosis and hepatitis B. Patients on azathioprine need thiopurine methyltransferase (TPMT) or NUDT15 assessment, since deficiency causes profound myelosuppression at standard doses.
Irritable Bowel Syndrome, Constipation, and Diarrhea
Irritable bowel syndrome is a disorder of gut-brain interaction diagnosed by recurrent abdominal pain related to defecation or a change in stool form or frequency, without alarm features. Management is subtype-directed: soluble fibre such as psyllium and, where appropriate, a low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet; antispasmodics for pain; polyethylene glycol for constipation-predominant disease; loperamide for diarrhea-predominant disease. Low-dose tricyclic antidepressants act as neuromodulators, not as antidepressant therapy.
Constipation management begins with fibre and fluid, then an osmotic agent (polyethylene glycol is preferred), with stimulants such as sennosides or bisacodyl for short-term rescue. Opioid-induced constipation does not adapt over time; start a stimulant laxative prophylactically at the same time as the opioid, and reserve peripherally acting mu-opioid receptor antagonists for refractory cases. Docusate has repeatedly failed to outperform placebo and should not be the recommendation.
Acute diarrhea is usually self-limiting; oral rehydration is the priority. Loperamide is inappropriate when there is bloody diarrhea or high fever, because slowing transit in invasive or toxin-mediated infection increases the risk of toxic megacolon and haemolytic uremic syndrome.
Nausea and Vomiting
Match the antiemetic to the mechanism:
- Motion sickness (vestibular): dimenhydrinate, scopolamine.
- Pregnancy: doxylamine-pyridoxine is the first-line and best-studied option in Canada.
- Chemotherapy-induced: 5-hydroxytryptamine-3 antagonists (ondansetron), neurokinin-1 antagonists (aprepitant), dexamethasone, and olanzapine in highly emetogenic regimens.
- Gastroparesis or delayed emptying: metoclopramide, limited to short courses because of tardive dyskinesia risk.
Ondansetron prolongs the QT interval; check for concurrent QT-prolonging drugs and electrolyte disturbance.
Cirrhosis and Its Complications
Portal hypertension drives most of the complications a pharmacist manages.
| Complication | First-line management | Monitoring |
|---|---|---|
| Ascites | Sodium restriction, spironolactone with furosemide in a 100:40 mg ratio | Weight, sodium, potassium, renal function |
| Spontaneous bacterial peritonitis | Third-generation cephalosporin plus intravenous albumin; ascitic polymorphonuclear count of 250/mm3 or more confirms | Fever, abdominal pain, encephalopathy |
| Hepatic encephalopathy | Lactulose titrated to 2 to 3 soft stools daily; add rifaximin for recurrence | Mental status, asterixis |
| Variceal bleeding prophylaxis | Non-selective beta-blocker (nadolol, propranolol, carvedilol) or band ligation | Heart rate, blood pressure |
Acetaminophen remains the preferred analgesic in stable cirrhosis at a reduced ceiling of about 2 g per day. NSAIDs are avoided because they precipitate renal failure and bleeding; benzodiazepines are avoided because they precipitate encephalopathy.
A 54-year-old man asks for something for six weeks of heartburn. He has lost 7 kg without trying and reports food 'sticking' in his throat. What is the appropriate action?
Why is clarithromycin-based triple therapy no longer recommended as first-line Helicobacter pylori eradication in Canada?
A patient has taken pantoprazole daily for four years for uninvestigated heartburn with no erosive disease and no NSAID use. The pharmacist plans to stop it. What must be included in counselling?
A patient with cirrhosis and ascites presents with fever and abdominal pain. Diagnostic paracentesis shows 480 polymorphonuclear cells per cubic millimetre. Which management is correct?