PH6.1-5 | Gastrointestinal Pharmacology — Glossary

An NK1 (neurokinin-1/substance P) receptor antagonist used as adjunct for delayed-phase CINV in highly emetogenic chemotherapy. Inhibits CYP3A4 — halve dexamethasone dose when combined.

A thiopurine immunomodulator prodrug → 6-mercaptopurine → 6-TGN (active, T-cell apoptosis inducer). Used for maintenance of IBD remission. Requires TPMT testing before starting. ADRs: myelosuppression, hepatotoxicity, pancreatitis, lymphoma risk.

A diphenylmethane stimulant laxative (prodrug activated by gut bacteria/esterases) that stimulates the myenteric plexus. Available as oral tablet (onset 6–12 h) and rectal suppository (onset 30–60 min). Do not take within 1 hour of milk or antacids (dissolves enteric coating prematurely).

A bismuth salt with direct bactericidal activity against H. pylori; used in quadruple eradication therapy. Colours stool and tongue black (bismuth sulphide) — a benign side effect. Avoid in severe renal impairment.

Agents (ispaghula/psyllium, methylcellulose) that absorb water, swell in the gut lumen, and increase stool bulk — stimulating peristalsis physiologically. Must be taken with adequate water. Safest class for long-term use.

A gram-positive anaerobic spore-forming bacterium that causes antibiotic-associated colitis. Produces toxins A (enterotoxin) and B (cytotoxin). Mild-moderate: oral metronidazole. Severe (WBC >15,000 or rising creatinine): oral vancomycin 125 mg four times daily × 10 days. Recurrent: fidaxomicin or FMT.

The area postrema on the floor of the fourth ventricle — a circumventricular organ outside the blood-brain barrier, directly exposed to blood-borne emetic stimuli. Expresses D2, 5-HT3, and NK1 receptors. Key target for antiemetics in CINV and opioid-induced nausea.

Nausea and vomiting induced by cytotoxic chemotherapy, classified into acute (0–24 h, 5-HT3-mediated), delayed (24–120 h, NK1-mediated), and anticipatory phases. Prophylaxis for highly emetogenic chemotherapy requires 5-HT3 antagonist + NK1 antagonist + dexamethasone.

A 5-HT4 agonist prokinetic withdrawn globally in 2000 due to hERG channel blockade causing fatal QT prolongation and torsades de pointes. Must not be prescribed.

A form of IBD with transmural, segmental inflammation that can affect any part of the GI tract. Hallmarks: skip lesions, cobblestone mucosa, fistulae, granulomas. Complications: strictures, fistulae, malabsorption (terminal ileum disease → B12 deficiency).

A hepatic cytochrome P450 enzyme that metabolises most PPIs and activates clopidogrel. Omeprazole and esomeprazole inhibit CYP2C19, potentially reducing clopidogrel activation and antiplatelet efficacy. Pantoprazole and rabeprazole are preferred with clopidogrel.

An opioid agonist anti-motility drug with partial CNS access, combined with subtherapeutic atropine (to deter abuse). Schedule H drug. Same contraindications as loperamide. Less preferred than loperamide in current practice.

A peripheral D2 antagonist prokinetic that does not significantly cross the BBB, making it safe in Parkinson's disease. Carries QT prolongation risk via hERG channel block. Maximum dose: 30 mg/day.

Movement disorder adverse effects of D2 antagonists arising from blockade of the nigrostriatal dopamine pathway: acute dystonia, akathisia, drug-induced parkinsonism (tremor, rigidity), and with chronic use, tardive dyskinesia (potentially irreversible orofacial/limb movements).

A macrocyclic antibiotic with narrow-spectrum activity against C. difficile, minimal systemic absorption. Preferred for recurrent C. difficile infection due to lower recurrence rates compared to vancomycin (achieves high colonic concentrations, spares Bacteroides spp.).

A condition defined by troublesome symptoms or complications caused by retrograde flow of gastric contents into the oesophagus, due to lower oesophageal sphincter dysfunction. First-line pharmacotherapy: PPI once daily before breakfast.

The proton pump enzyme on the luminal membrane of the gastric parietal cell canaliculus that actively secretes H⁺ into the gastric lumen in exchange for K⁺. It is the final common effector of acid secretion and the target of PPIs.

A drug (famotidine, cimetidine, nizatidine) that competitively and reversibly blocks histamine H₂ receptors on the parietal cell, reducing acid secretion with less potency than PPIs.

A Gram-negative urease-producing spiral bacterium that colonises the gastric antrum in ~70% of Indian PUD patients; the most important aetiological agent of peptic ulcer disease and a carcinogen (gastric cancer). Eradication with antibiotics cures most Hp-positive ulcers.

The human ether-à-go-go-related gene potassium channel responsible for cardiac repolarisation (IKr current). Blockade by drugs prolongs the QT interval, predisposing to torsades de pointes. Relevant to cisapride (withdrawn) and domperidone (restricted).

A muscarinic M1 antagonist used transdermally for motion sickness prophylaxis. Applied as a patch behind the ear 4 hours before travel. Most effective single agent for motion sickness. Causes anticholinergic ADRs.

Abnormally low serum magnesium, a clinically significant ADR of long-term PPI use. It may present as muscle cramps, arrhythmias, and tetany, and is often refractory to oral Mg supplementation. Severe cases require PPI cessation.

A functional GI disorder with recurrent abdominal pain associated with defaecation changes, normal colonoscopy, and normal inflammatory markers. Subtypes: IBS-D, IBS-C, IBS-M. No immunosuppression; treatment targets motility (loperamide, linaclotide), pain (mebeverine, amitriptyline), and microbiome (rifaximin).

A chimeric (25% murine/75% human) IgG1 monoclonal antibody against TNF-α, given by IV infusion. Used for moderate-severe UC and CD. Requires pre-treatment TB screening (IGRA) and hepatitis B screening. Risk: reactivation of latent TB, opportunistic infections.

A non-absorbable synthetic disaccharide fermented by colonic bacteria to SCFA and gas, producing an osmotic laxative effect and acidifying the colon. Used for constipation (onset 24–48 h) and hepatic encephalopathy (traps NH4+ in the acidified colon). Main ADRs: bloating, flatulence.

A GC-C (guanylate cyclase-C) receptor agonist that increases intracellular cGMP, activating CFTR (Cl- secretion into lumen) and reducing visceral pain afferent activity. Approved for IBS-C and chronic idiopathic constipation. Main ADR: diarrhoea.

A peripheral mu-opioid receptor agonist (synthetic) that reduces intestinal motility and increases anal sphincter tone without CNS effects (expelled from CNS by P-glycoprotein). Effective for non-invasive diarrhoea in adults. Absolutely contraindicated in invasive/bloody/febrile diarrhoea and in children under 2.

A ClC-2 (chloride channel type 2) activator that increases apical Cl- secretion from intestinal epithelial cells, drawing water into the gut lumen. Approved for chronic idiopathic constipation and IBS-C. Main ADR: nausea.

A direct smooth muscle relaxant (blocks Na+ channels in colonic smooth muscle) used as first-line antispasmodic in IBS for abdominal cramps. No anticholinergic side effects. First-line antispasmodic per NICE IBS guidelines.

Brown-black discolouration of colonic mucosa from lipofuscin-laden macrophages, seen after prolonged anthraquinone laxative (senna, cascara) use. Benign and reversible on stopping the laxative. Its presence at colonoscopy implies chronic stimulant laxative use.

Pure 5-aminosalicylic acid — the active anti-inflammatory moiety for UC. Better tolerated than sulfasalazine (no sulphapyridine carrier). Mechanism: local NF-κB inhibition, leukotriene blockade in colonic mucosa. First-line for mild-moderate UC.

A peripherally acting mu-opioid receptor antagonist (PAMORA) that does not cross the BBB. Given subcutaneously for opioid-induced constipation. Blocks mu-opioid receptors in the enteric nervous system without reversing central analgesia.

A dopamine D2 antagonist and 5-HT4 agonist prokinetic/antiemetic that crosses the BBB. Effective for CINV, gastroparesis, and GERD-related nausea but causes extrapyramidal symptoms (EPS). Maximum recommended course: 5 days.

A synthetic prostaglandin E₁ (PGE₁) analogue that enhances gastric mucosal protection by stimulating mucus and bicarbonate secretion and reducing acid output. Contraindicated in pregnancy (uterotonic). Used for NSAID-induced ulcer prevention and as an abortifacient.

A probable human carcinogen that forms as a degradation product in ranitidine tablets over time. Its detection led to the global market withdrawal of ranitidine in 2020. Famotidine is the current H2RA of choice.

A drug class (aprepitant, fosaprepitant) that blocks NK1 receptors in the NTS and CTZ where substance P mediates the delayed phase of CINV. Used in combination with 5-HT3 antagonists for highly emetogenic chemotherapy.

A competitive 5-HT3 receptor antagonist effective for CINV (acute phase), PONV, and radiation-induced nausea. Causes constipation and mild QT prolongation. Not effective for motion sickness.

The WHO low-osmolarity formula (245 mOsm/L: glucose 75 + Na 75 + K 20 + Cl 65 + citrate 10 mmol/L) for preventing and treating dehydration in diarrhoea. Mechanism: SGLT1 sodium-glucose cotransport drives water absorption even when cholera toxin is maximally activating CFTR chloride secretion.

Agents that create an osmotic gradient drawing water into the gut lumen. Sub-groups: poorly-absorbed salts (Mg(OH)2 — avoid in renal failure), non-absorbable sugars (lactulose — gas, hepatic encephalopathy use), PEG/macrogol (inert, preferred for long-term use).

An inert high-molecular-weight polymer osmotic laxative that binds water by hydrogen bonding. Not absorbed or fermented (no gas). Preferred osmotic agent for long-term use and bowel preparation. Safe in renal failure (unlike Mg salts).

A class of drugs (omeprazole, pantoprazole, rabeprazole, lansoprazole, esomeprazole) that irreversibly inhibit the H⁺/K⁺-ATPase enzyme (proton pump) in the gastric parietal cell canaliculus, providing the most powerful acid suppression available.

A highly selective 5-HT4 receptor agonist acting on colonic smooth muscle; approved for chronic constipation in adults. Not used as an antiemetic. No cardiac arrhythmia risk (does not block hERG).

A second-line or clarithromycin-resistant-region eradication regimen: PPI + bismuth subcitrate + tetracycline 500 mg + metronidazole 400 mg for 10–14 days.

An enkephalinase inhibitor that prevents breakdown of gut enkephalins, enhancing their antisecretory effect on intestinal epithelial cells (reduced cAMP-driven Cl- secretion). No anti-motility effect — safe alternative to loperamide in paediatric acute diarrhoea. WHO-endorsed.

An increase in gastric acid output above pre-treatment levels following abrupt discontinuation of prolonged PPI therapy, due to upregulation of proton pumps and hypergastrinaemia during PPI use. Managed by gradual step-down.

A non-absorbable rifamycin antibiotic (<0.4% systemic bioavailability) that acts entirely within the gut lumen. Used for IBS-D (particularly with suspected SIBO/dysbiosis) and travellers' diarrhoea (non-invasive). Does not cause systemic antibiotic side effects.

An anthraquinone glycoside stimulant laxative (sennosides A and B) converted to active anthranols by colonic bacteria. Stimulates the myenteric plexus. Onset 6–12 h oral. Safe for occasional use; long-term use can cause melanosis coli. Limited use in pregnancy (low absorption).

An apical membrane cotransporter on intestinal enterocytes that co-transports 2 Na+ with 1 glucose molecule into the cell. Its activity is independent of cAMP/cGMP signalling, so it remains functional in cholera — the basis of ORS efficacy.

An aluminium salt of sucrose octasulphate that forms an adherent viscous barrier over the ulcer base in acid pH, protecting it from further acid/pepsin attack. Not an acid suppressant; requires acidic environment for activation.

An azo-bond prodrug of 5-ASA + sulphapyridine. Colonic bacteria cleave the bond → free 5-ASA (active) + sulphapyridine (carrier, source of ADRs: haemolysis, male infertility, nausea). Requires folic acid 5 mg/day supplementation.

A JAK1/3 inhibitor (oral small molecule) approved for moderate-severe UC. Blocks JAK-STAT signalling from multiple pro-inflammatory cytokine receptors (IL-6, IFN-γ, others). Risks: herpes zoster reactivation, dyslipidaemia, cardiovascular risk.

Life-threatening dilation of the colon (transverse diameter >6 cm) with systemic toxicity, occurring as a complication of inflammatory colitis (C. difficile, Shigella, IBD). Risk is dramatically increased by anti-motility agents (loperamide, diphenoxylate) in invasive colitis — hence the absolute contraindication.

An enzyme that inactivates 6-thioguanine nucleotides (6-TGN), the active metabolites of azathioprine/6-MP. TPMT-deficient patients cannot inactivate 6-TGN → severe myelosuppression at standard doses. TPMT activity must be measured before prescribing azathioprine.

The first-line H. pylori eradication regimen: PPI + amoxicillin 1 g + clarithromycin 500 mg, all twice daily for 14 days.

A form of IBD with continuous mucosal inflammation limited to the colon, starting from the rectum. Hallmarks: bloody diarrhoea, rectal urgency. First-line treatment: mesalazine (oral + topical). Long-term risk: colorectal cancer proportional to extent and duration.

A humanised anti-α4β7 integrin monoclonal antibody that blocks gut-homing lymphocyte trafficking into the intestinal mucosa. Gut-selective: lower systemic infection risk than anti-TNF. Approved for moderate-severe UC and CD.

WHO/UNICEF recommendation for children under 5 with acute diarrhoea: 20 mg elemental zinc per day for 10–14 days. Reduces duration and severity of the diarrhoeal episode and prevents recurrence for 2–3 months by restoring intestinal mucosal immunity.

A condition caused by a gastrin-secreting tumour (gastrinoma, usually pancreatic or duodenal), leading to massively elevated gastric acid output, multiple refractory peptic ulcers, and sometimes diarrhoea. Treated with high-dose PPI.