PH6.1-5 | Gastrointestinal Pharmacology — Graded Quiz

Correct. PPIs are weak bases that concentrate in the highly acidic secretory canaliculi (pH 1–2) of stimulated parietal cells, where they undergo protonation to form the active sulfenamide. This is why PPIs must be taken 30–60 minutes before meals — they require an active, acid-secreting parietal cell population.

Acid-trapping mechanism: PPI (weak base, pKa ~4) → enters secretory canaliculus (pH 1–2) → protonated → sulfenamide → covalent S–S bond with proton pump. Only active, meal-stimulated pumps are targeted — hence pre-meal dosing.

Incorrect. PPIs require the highly acidic environment of the secretory canaliculus to be activated (converted to sulfenamide). They do not act in neutral-pH cellular compartments or on other cell types.

Correct. Sucralfate (sucrose octasulfate–aluminium complex) polymerises in an acidic environment (pH <4) to form a sticky, viscous gel that selectively binds to the base of ulcer craters (particularly to denatured proteins at the crater floor), creating a physical barrier against acid, pepsin, and bile. It also stimulates prostaglandin synthesis and bicarbonate secretion.

Sucralfate is a 'local' drug: it works only in an acidic environment, acts only at the site of mucosal injury, and is not significantly absorbed systemically. Because it requires acid for activation, it should NOT be given simultaneously with PPIs or antacids — space doses by at least 2 hours.

Incorrect. Sucralfate does not suppress acid secretion — it requires acid for activation. Its mechanism is physical protection of the ulcer base, not receptor antagonism or acid neutralisation.

Correct. Ondansetron is a selective 5-HT₃ receptor antagonist. It blocks 5-HT₃ receptors on vagal afferents in the gut (preventing the 'gut signal' from reaching the brainstem NTS) and on the chemoreceptor trigger zone. This dual peripheral + central blockade is the basis of its efficacy against chemotherapy-induced and postoperative nausea.

Receptor-antiemetic map: 5-HT₃ → ondansetron/granisetron (chemotherapy, PONV); NK₁ → aprepitant (delayed CINV); D₂ → metoclopramide, domperidone (gastroparesis, mild PONV); H₁/M₁ → promethazine, cyclizine (motion sickness, pregnancy NVP).

Incorrect. Ondansetron's specific receptor is 5-HT₃. D₂ antagonism = metoclopramide, domperidone; H₁ antagonism = promethazine, cyclizine; NK₁ antagonism = aprepitant.

Correct. Motion sickness is driven by mismatch signals from the vestibular apparatus → H₁ and M₁ receptors in the vomiting pathway. Promethazine (H₁/M₁ antagonist) or hyoscine (anticholinergic) are the drugs of choice. Promethazine must be given 1–2 hours before travel to be effective prophylactically.

The receptor pathway determines which drug works. Motion sickness = vestibular pathway = H₁/M₁ → promethazine or hyoscine. CINV = gut 5-HT₃ + CTZ NK₁ → ondansetron + aprepitant. Gastroparesis/PONV = D₂ → domperidone/metoclopramide. Choosing an ondansetron for motion sickness is one of the most common exam errors.

Incorrect. 5-HT₃ antagonists (ondansetron) and D₂ antagonists (domperidone) do not act on the H₁/M₁ vestibular pathway — they are ineffective for motion sickness. Metoclopramide IV is not appropriate for prophylaxis in an outpatient setting.

Correct. Loperamide activates peripheral mu-opioid receptors in the myenteric plexus, reducing longitudinal (propulsive) peristalsis and increasing segmental contractions and internal anal sphincter tone. It does not cross the blood-brain barrier at therapeutic doses, so it has no central opioid effects (no analgesia, sedation, or addiction at normal doses).

Loperamide = peripheral mu-opioid agonist. Non-absorbable at standard doses. Highly effective for non-invasive (secretory/osmotic) diarrhoea. Absolutely contraindicated in dysentery (bloody + febrile diarrhoea) — prolonged contact of invading organisms with an inflamed mucosa increases toxin absorption and complication risk.

Incorrect. Loperamide's mechanism is mu-opioid receptor activation in the gut — the same receptor family as morphine, but with peripheral selectivity. This is why it is structurally related to pethidine yet lacks central opioid effects.

Correct. WHO recommends zinc 20 mg/day for 10–14 days for children >6 months with acute diarrhoea (10 mg/day for infants 2–6 months). Zinc reduces duration of the current episode by ~25% and incidence of diarrhoea in the following 2–3 months. It is recommended alongside ORS for all acute diarrhoeal episodes in children in low- and middle-income countries.

Zinc + ORS = the two-pillar package for childhood diarrhoea in low-income settings. Zinc mechanisms include: restoration of intestinal mucosal integrity, improvement of immune function, reduction of gut secretion. The 10–14 day duration (beyond the diarrhoeal episode) is deliberate — it rebuilds immune competence.

Incorrect. The WHO dose is 20 mg/day for 10–14 days in children >6 months. The 14-day course is important — it replenishes depleted zinc stores and provides protection against reinfection beyond the current episode.

Correct. Bisacodyl (diphenylmethane stimulant laxative) activates enteric neurons in the myenteric plexus and directly stimulates colonic mucosal cells, increasing propulsive peristalsis. It also inhibits water and electrolyte absorption from the colonic mucosa, increasing luminal secretion — a dual mechanism producing rapid (6–12 h oral; 15–60 min suppository) onset.

Laxative class classification by mechanism: Bulk-forming (ispaghula, methylcellulose) → increase stool mass. Osmotic (PEG, lactulose, MgSO₄) → retain water in lumen. Stimulant (bisacodyl, senna) → activate enteric neurons + mucosal secretion — fastest onset, used for acute constipation. Stool softeners (docusate) → surfactant, reduce surface tension.

Incorrect. Bisacodyl is a STIMULANT laxative — it activates enteric neurons and stimulates mucosal electrolyte secretion. Osmotic retention describes PEG/lactulose; surfactant action describes docusate; bulk addition describes psyllium/ispaghula.

Correct. Lactulose (galactose–fructose disaccharide) cannot be hydrolysed by human intestinal disaccharidases and reaches the colon intact. Colonic bacteria ferment it to lactic, acetic, and formic acids + CO₂. The resulting acidification and increased osmolality in the colon retains water in the lumen, softening stool. This same mechanism also lowers colonic pH and traps ammonia (NH₄⁺) — the basis of its use in hepatic encephalopathy.

Lactulose's dual utility: (1) Osmotic laxative for chronic constipation; (2) Reduces blood ammonia in hepatic encephalopathy (colonic acidification traps NH₃ as NH₄⁺, preventing absorption). Downside: fermentation produces gas → bloating and flatulence in ~20% of patients — counsel before prescribing.

Incorrect. Lactulose is not absorbed, not metabolised by human enzymes, and does not act centrally or as a lubricant. Its mechanism is fermentation-driven osmotic water retention in the colon.

Correct. IBD is defined by organic, histologically confirmed mucosal inflammation (crypt abscesses, goblet cell depletion, transmural inflammation in Crohn's). IBS has no detectable organic pathology — it is a functional gut disorder (altered motility + visceral hypersensitivity + gut-brain axis dysregulation). This distinction drives fundamentally different pharmacology: IBD requires anti-inflammatory/immunosuppressive drugs; IBS requires symptom modulators (antispasmodics, low-dose antidepressants, fibre).

IBD = inflammation (UC: mucosal, continuous, colonic; CD: transmural, skip lesions, any site) → treat the inflammation. IBS = functional (altered sensorimotor function, no inflammation) → modulate symptoms. NEVER give corticosteroids, immunosuppressants, or biologics for IBS — they treat inflammation that does not exist and cause harm without benefit.

Incorrect. Symptom severity, age, and dietary response overlap considerably between IBD and IBS. The defining and pharmacologically decisive distinction is the PRESENCE or ABSENCE of organic mucosal inflammation.

Correct. TPMT testing is mandatory before azathioprine because ~0.3% of the population are TPMT-deficient (homozygous poor metabolisers) and cannot convert 6-thioguanine nucleotides (6-TGN) via the methylation pathway. In these patients, 6-TGN accumulates to toxic levels, causing severe, potentially fatal myelosuppression (pancytopenia). TPMT testing allows dose individualisation or avoidance in poor metabolisers.

Drug-specific pre-treatment safety checks: AZATHIOPRINE → TPMT (pharmacogenomics: prevent fatal myelosuppression). ANTI-TNF biologics → TB screening (prevent fatal reactivation TB). METHOTREXATE → LFTs + renal function (prevent hepatotoxicity, nephrotoxicity). Mixing these up is a high-stakes clinical error.

Incorrect. TB screening (QuantiFERON + CXR) is mandatory before ANTI-TNF BIOLOGICS (infliximab, adalimumab), not before azathioprine. TPMT testing is the specific pharmacogenomic safety check for thiopurine drugs.