PH6.1-5 | Gastrointestinal Pharmacology — Practice Quiz

Correct. PPIs are prodrugs that require acid activation; the resulting sulfenamide covalently binds to cysteine residues on the H⁺/K⁺-ATPase, producing irreversible inhibition that lasts until new pump protein is synthesised (~18–24 h). This is why PPIs must be taken before meals.

PPIs are the most potent acid-suppressing agents because they block the final common pathway of acid secretion regardless of which stimulant (histamine, acetylcholine, or gastrin) is active. Irreversible binding explains their prolonged duration despite a short plasma half-life.

Incorrect. PPIs act on the proton pump (H⁺/K⁺-ATPase), not on H₂ receptors, and are not antacids. Their covalent, irreversible binding distinguishes them from all other acid-suppressive drugs.

Correct. Standard first-line triple therapy for H. pylori is a PPI + amoxicillin + clarithromycin for 14 days. A PPI is essential — it raises intragastric pH, increasing the stability and local concentration of both antibiotics, improving eradication rates from ~50% (antibiotics alone) to ~80–90%.

In H. pylori eradication, the PPI is not merely adjunctive — it is pharmacodynamically essential. The antibiotics work best at neutral pH; without a PPI, acid degradation reduces antibiotic bioavailability at the gastric mucosa. Ranitidine was globally withdrawn in 2020 (NDMA contamination) and must not be used.

Incorrect. First-line H. pylori eradication requires a PPI plus TWO antibiotics. The WHO-endorsed standard first-line regimen (where clarithromycin resistance is <15%) is PPI + amoxicillin + clarithromycin for 14 days.

Correct. Cisplatin is highly emetogenic, triggering massive intestinal 5-HT₃ release. The evidence-based backbone for acute cisplatin-induced emesis is a 5-HT₃ antagonist (ondansetron/granisetron) + dexamethasone; the NK₁ antagonist aprepitant is added for highly emetogenic regimens to cover delayed emesis (24–120 h post-chemotherapy).

Match the antiemetic to the dominant pathway. Cisplatin activates gut vagal 5-HT₃ receptors AND the CTZ NK₁ pathway. For acute phase: 5-HT₃ blocker + steroid. For delayed phase (days 2–5): NK₁ blocker (aprepitant) + steroid. Promethazine and domperidone act on D₂/H₁ receptors and are insufficient for highly emetogenic chemotherapy.

Incorrect. Cisplatin-induced emesis is driven primarily by intestinal enterochromaffin cell 5-HT₃ release. Antihistamines and prokinetics are inadequate for this mechanism; 5-HT₃ antagonists are the pharmacological cornerstone.

Correct. Metoclopramide's prokinetic effect is primarily mediated by D₂ receptor antagonism in the gut, which disinhibits acetylcholine release from myenteric plexus neurons, enhancing antral and pyloric motility. It also has 5-HT₃ antagonist and 5-HT₄ agonist effects at higher doses.

Metoclopramide = D₂ antagonist (primary prokinetic) + weak 5-HT₃ antagonist + 5-HT₄ agonist. The D₂ antagonism at the CTZ also explains its antiemetic effect. Central D₂ antagonism causes extrapyramidal side effects (tardive dyskinesia, acute dystonia) — limiting long-term use. Domperidone shares D₂ antagonism but doesn't cross the BBB, so extrapyramidal effects are absent.

Incorrect. Metoclopramide's primary mechanism is D₂ receptor antagonism. While it has some 5-HT₄ agonist activity, this is secondary. Pure 5-HT₄ agonism describes cisapride and tegaserod.

Correct. Loperamide is absolutely contraindicated in invasive (dysenteric) diarrhoea with fever in children. By inhibiting peristalsis, loperamide prolongs mucosal contact with enteroinvasive pathogens (Shigella, E. coli O157:H7), worsening systemic absorption of toxins and increasing risk of haemolytic-uraemic syndrome and toxic megacolon.

Anti-motility drugs (loperamide, diphenoxylate) are safe ONLY in non-invasive (secretory/osmotic) diarrhoea — watery, afebrile, no blood, no pus. Blood + fever + pus cells = dysentery = invasive = NEVER use loperamide. ORS is always appropriate regardless of type.

Incorrect. ORS, zinc, and appropriate antibiotics are all appropriate here. Loperamide is the dangerous choice — anti-motility agents prolong pathogen contact with an already inflamed and invaded mucosa.

Correct. SGLT1 (sodium–glucose linked transporter 1) co-transports one glucose with one sodium across the apical membrane of the enterocyte. This electrogenic process creates an intracellular gradient that drives water absorption even in secretory diarrhoea, because cholera toxin's cAMP mechanism specifically blocks the NHE3 sodium–hydrogen exchanger but leaves SGLT1 intact.

ORS is one of the most important pharmacological discoveries of the 20th century. It reduced cholera case fatality from 50–70% to <1% when properly administered. The key principle: cholera toxin blocks NHE3 but NOT SGLT1. Glucose opens a separate sodium door. This is why hypotonic rice-based or glucose-containing ORS outperforms plain saline.

Incorrect. The reason for the glucose–sodium combination is pharmacological, not nutritional. SGLT1-coupled absorption drives water uptake even against the secretory drive of cholera toxin — ORS works by an entirely different sodium transport pathway.

Correct. PEG (polyethylene glycol / macrogol) is the preferred osmotic laxative in pregnancy. It is not absorbed, is not metabolised, and does not stimulate uterine contractions. It works by retaining water in the colon through an osmotic mechanism and is the most evidence-based choice for constipation in pregnancy.

Pregnancy laxative safety rule: SAFE = bulk-forming (ispaghula with water) or osmotic (PEG, lactulose with caution). AVOID = stimulant laxatives (senna, bisacodyl) and castor oil (stimulate uterine contractions); avoid prolonged mineral oil (fat-soluble vitamin malabsorption). PEG is the guideline-recommended agent.

Incorrect. Both senna and castor oil can stimulate uterine contractions and are avoided in pregnancy, particularly in the third trimester. Docusate sodium has been associated with neonatal hypomagnesaemia. PEG is the safest choice.

Correct. Both are true and causally linked. Ispaghula husk (psyllium) is a hygroscopic polysaccharide that absorbs up to 50× its weight in water; without adequate fluid, it forms a viscous mass that can cause oesophageal obstruction (particularly if taken by a patient with dysphagia or in the supine position). The clinical counselling point is mandatory.

Bulk-forming laxatives are safe long-term and ideal for chronic constipation, IBS, and pregnancy — BUT the water instruction is life-saving, not optional. There are case reports of oesophageal and intestinal obstruction when taken dry. Always counsel: 'Take with at least 200–250 mL of water and remain upright for 30 minutes.'

Incorrect. Both the assertion and reason are true, and the reason directly and correctly explains the risk that makes the instruction clinically necessary.

Correct. Mesalazine (5-aminosalicylic acid) is the first-line maintenance agent for mild-to-moderate UC. For left-sided/distal disease, the combination of oral + topical (suppository or enema) achieves higher mucosal concentrations in the affected segment. Aminosalicylates must be continued long-term — stopping leads to relapse in >80% of patients within 12 months.

UC maintenance ladder: 5-ASA first (all disease extents) → add azathioprine/6-MP if steroid-dependent → biologic (infliximab/vedolizumab) for steroid-refractory or biologic-eligible. Steroids are for induction ONLY — never maintenance. For distal UC, the topical route is particularly important for achieving adequate mucosal drug levels.

Incorrect. Corticosteroids are NOT appropriate for maintenance — they do not prevent relapse and long-term use causes adrenal suppression, osteoporosis, diabetes, and cataracts. Azathioprine and biologics are reserved for steroid-dependent or steroid-refractory disease.

Correct. TB screening is an absolute pre-requisite before starting ANY anti-TNF therapy (infliximab, adalimumab, etanercept). TNF-α is critical for forming and maintaining granulomas that contain Mycobacterium tuberculosis. Anti-TNF therapy dissolves these granulomas, releasing bacilli and causing potentially fatal reactivation tuberculosis. India is a high-TB-burden country — this rule is non-negotiable.

Before ANY biologic: SCREEN FOR TB (Mantoux/IGRA + CXR). Before azathioprine: check TPMT enzyme activity (to prevent fatal myelosuppression in poor metabolisers). These are two separate pre-treatment safety rules that target two different drugs. In India, where TB prevalence is high, the anti-TNF TB screening rule must be drilled as an absolute reflex.

Incorrect. While colonoscopy and TPMT have their roles, the mandatory pre-biologic step is tuberculosis screening. This is a patient safety issue with life-threatening consequences if omitted.