For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
MAKINDO MEDICINE · Gastroenterology & Hepatology35 / 268
Gastroenterology: Anatomy Physiology Pharmacology
🍽️ Gastrointestinal anatomy, physiology and pharmacology -the gut digests food, absorbs nutrients and water, and gets rid of waste; the liver processes almost everything absorbed, including most drugs. Knowing the blood supply, the portal circulation, where things are absorbed and what the liver does explains most GI symptoms, blood tests and complications. Most GI drugs reduce acid, stop vomiting, change bowel movement, calm gut inflammation or treat liver disease.
Your four questions for every drug: How does it work? What is it used for? What are the important side effects and safety issues? What does it interact with, and how is it monitored?
The Gut Wall and Enteric Nervous System
Four layers from inside out:
Mucosa -epithelium (absorbs and secretes), lamina propria (immune cells), muscularis mucosae. Most cancers and inflammation start here.
Submucosa -blood vessels, lymphatics, the submucosal (Meissner's) plexus (controls secretion and blood flow).
Muscularis propria -inner circular and outer longitudinal muscle, with the myenteric (Auerbach's) plexus between them (controls movement).
Serosa (peritoneum) -or adventitia where there is no peritoneum (oesophagus, retroperitoneal parts) -the oesophagus has no serosa, so cancer spreads and leaks more easily.
Enteric nervous system -the "gut brain" (about as many neurons as the spinal cord); works on its own but is adjusted by the autonomic nerves:
Parasympathetic (vagus, and sacral nerves S2–S4 for the distal colon) -increases movement and secretion.
Loss of the myenteric plexus -achalasia (oesophagus), Hirschsprung's disease (colon, from birth), Chagas disease.
Interstitial cells of Cajal -the gut's pacemaker cells (origin of GIST tumours -KIT-positive, treated with imatinib).
Visceral pain -poorly localised, felt in the midline according to embryological origin (foregut -epigastric; midgut -around the umbilicus; hindgut -suprapubic); becomes localised when the parietal peritoneum is inflamed (e.g. appendicitis moving to the right iliac fossa).
Oesophagus -about 25 cm long, from C6 (cricopharyngeus) to the stomach at about T10–T11; about 40 cm from the incisors to the gastro-oesophageal junction at endoscopy.
Upper third -skeletal muscle; lower third -smooth muscle (so myasthenia and stroke affect the top; achalasia and scleroderma the bottom).
Three narrowings where food and tablets stick -cricopharyngeus (15 cm), where the aortic arch and left main bronchus cross (25 cm), and the diaphragm (40 cm).
Lower oesophageal sphincter -a high-pressure zone helped by the diaphragm crura; weakened by hiatus hernia, smoking, alcohol, fatty food, pregnancy, calcium channel blockers, nitrates and anticholinergics → reflux.
Lining -squamous epithelium; in Barrett's oesophagus it changes to columnar (intestinal metaplasia) from chronic acid -risk of adenocarcinoma.
Lower oesophageal veins link portal and systemic veins -varices in portal hypertension.
Stomach -cardia, fundus, body, antrum and pylorus:
Parietal cells (body and fundus) -acid and intrinsic factor.
Chief cells -pepsinogen.
G cells (antrum) -gastrin.
ECL cells -histamine (stimulates parietal cells).
D cells -somatostatin (inhibits acid).
Mucous cells -protective mucus and bicarbonate.
Blood supply of the stomach -all from the coeliac trunk (left and right gastric along the lesser curve; gastroepiploic arteries along the greater curve; short gastrics to the fundus). A posterior duodenal ulcer can erode the gastroduodenal artery → major bleeding.
About 6 metres long -duodenum (about 25 cm), jejunum (about 2.5 m), ileum (about 3.5 m). A huge surface area (folds, villi and microvilli -about 30 m²) for absorption.
Duodenum -C-shaped around the head of the pancreas; mostly retroperitoneal; the bile duct and pancreatic duct open at the ampulla of Vater (second part). Brunner's glands make alkaline mucus.
Jejunum -thicker wall, more folds, long vasa recta; absorbs most nutrients.
Ileum -more fat in the mesentery, lymphoid tissue (Peyer's patches); the terminal ileum absorbs vitamin B12 and bile acids (the reason Crohn's disease and ileal resection cause B12 deficiency and bile acid diarrhoea).
Ileocaecal valve -slows emptying into the colon and limits backflow of bacteria (its removal increases bacterial overgrowth).
Villus atrophy (coeliac disease) -flattened villi, fewer brush border enzymes → malabsorption (iron, folate, calcium) and lactose intolerance; mainly affects the duodenum and jejunum, so duodenal biopsy confirms it.
Meckel's diverticulum -remnant of the vitelline duct; "rule of 2s" (2% of people, 2 feet from the ileocaecal valve, 2 inches long, may contain 2 types of ectopic tissue -gastric and pancreatic); can cause painless bleeding in children (technetium scan).
Short bowel syndrome -usually under about 200 cm of small bowel left; loss of fluid, magnesium and nutrients; may need parenteral nutrition.
About 1.5 metres -caecum and appendix, ascending, transverse, descending and sigmoid colon, rectum, anal canal.
Intraperitoneal parts (have a mesentery -can twist) -transverse and sigmoid colon (sigmoid volvulus, especially in older people with chronic constipation), caecum in some people (caecal volvulus). Ascending and descending colon are retroperitoneal.
Features -taeniae coli (three bands of longitudinal muscle, which meet at the appendix base), haustra, appendices epiploicae.
Appendix -base at McBurney's point (one-third of the way from the anterior superior iliac spine to the umbilicus); tip position varies (retrocaecal appendicitis can cause atypical pain).
Functions -absorbs water and salt (about 1–1.5 L a day), stores faeces, ferments fibre into short-chain fatty acids (fuel for colon cells).
Rectum -about 12–15 cm; stretch receptors give the urge to defecate.
Dentate (pectinate) line in the anal canal -the boundary between gut-derived and skin-derived tissue:
Above -columnar lining, visceral nerves (painless) -internal haemorrhoids are painless; adenocarcinoma; drains to internal iliac and portal veins and nodes.
Below -squamous lining, somatic nerves (painful) -anal fissures, external haemorrhoids and squamous cancer are painful; lymph drains to the inguinal nodes.
Anal sphincters -internal (smooth muscle, involuntary -tight in fissures, relaxed by GTN and diltiazem) and external (skeletal, voluntary -pudendal nerve; damaged in childbirth → faecal incontinence).
Lower oesophagus to the 2nd part of the duodenum (ampulla), liver, gallbladder, pancreas (part), spleen
Epigastrium
Midgut
Superior mesenteric artery (L1)
Ampulla to two-thirds of the way along the transverse colon (small bowel, caecum, appendix, ascending colon)
Around the umbilicus
Hindgut
Inferior mesenteric artery (L3)
Distal transverse colon to the upper anal canal
Suprapubic
Coeliac trunk branches -left gastric, splenic, common hepatic.
Watershed areas (between two arterial territories) -the splenic flexure and the rectosigmoid junction -most vulnerable to ischaemic colitis in low blood pressure (left-sided pain and bloody diarrhoea in older people).
Acute mesenteric ischaemia -usually SMA embolism (AF) or thrombosis; pain out of proportion to the examination, raised lactate (late); CT angiography urgently.
Chronic mesenteric ischaemia -"intestinal angina": pain 15–30 minutes after eating, fear of food, weight loss.
Rectum and anus -superior rectal (from IMA), middle rectal and inferior rectal arteries (from internal iliac).
Gut blood flow is about 25% of cardiac output at rest, rising after meals; it falls early in shock (the gut is sacrificed to protect the brain and heart).
Portal vein -formed behind the neck of the pancreas by the superior mesenteric vein and the splenic vein (the inferior mesenteric vein usually joins the splenic vein).
Carries nutrient-rich blood from the gut, spleen and pancreas to the liver -about 75% of liver blood flow (the hepatic artery supplies the other 25%, but about half the oxygen).
First-pass metabolism -drugs absorbed from the gut go through the liver before reaching the body -so some drugs are much less active when swallowed (e.g. GTN is given under the tongue; morphine and propranolol have low oral availability).
Portosystemic anastomoses -places where portal and systemic veins connect; they enlarge in portal hypertension:
Lower oesophagus and gastric fundus (left gastric to azygos veins) -varices -life-threatening bleeding.
Umbilicus (paraumbilical to abdominal wall veins) -caput medusae.
Rectum (superior rectal to middle and inferior rectal) -rectal varices (different from haemorrhoids).
The largest internal organ (about 1.5 kg) -under the right ribs, held by the falciform ligament; the bare area touches the diaphragm.
Couinaud segments -8 functional segments, each with its own portal and arterial branch and bile duct -allows surgical removal of parts of the liver. The right and left halves are divided by a line through the gallbladder and IVC (Cantlie's line), not the falciform ligament.
Porta hepatis -the portal vein, hepatic artery and common bile duct (the portal triad) enter and leave here.
Microscopic structure -the acinus:
Blood flows from the portal triads (zone 1 -most oxygen) through the sinusoids to the central vein (zone 3 -least oxygen).
Zone 3 has the most CYP450 enzymes and least oxygen -first damaged by paracetamol (NAPQI), ischaemia (shock liver) and alcohol.
Zone 1 -damaged by some toxins and in viral hepatitis.
Cells:
Hepatocytes -metabolism, synthesis, bile production.
Kupffer cells -macrophages that filter bacteria from portal blood.
Hepatic stellate cells -store vitamin A; become activated and lay down collagen in liver injury → fibrosis and cirrhosis.
Sinusoidal endothelial cells -leaky "windows" let proteins pass between blood and hepatocytes.
Regeneration -the healthy liver can regrow after up to about two-thirds is removed (the basis of living donor transplants).
Liver pain -from stretching of the capsule (hepatitis, congestion in heart failure, Budd–Chiari).
Bile duct tree -right and left hepatic ducts → common hepatic duct → joined by the cystic duct → common bile duct (CBD; normal diameter under about 6 mm, larger in older people and after cholecystectomy) → passes behind the duodenum and through the head of the pancreas → joins the pancreatic duct at the ampulla of Vater, controlled by the sphincter of Oddi.
Gallbladder -stores and concentrates bile (about 30–50 mL); contracts after fatty meals (stimulated by CCK) -the reason biliary pain follows fatty food.
Calot's triangle -cystic duct, common hepatic duct and the underside of the liver; contains the cystic artery (usually from the right hepatic artery) -identified in cholecystectomy to avoid bile duct injury.
Gallbladder pain -felt in the right upper quadrant and epigastrium, referred to the right shoulder tip (diaphragm irritation) or between the shoulder blades. Murphy's sign -pain stops breath-in when pressing under the right ribs (acute cholecystitis).
Gallstones in the CBD -obstructive jaundice, cholangitis (Charcot's triad -fever, jaundice, RUQ pain), pancreatitis (stone at the ampulla).
Courvoisier's law -a palpable, non-tender gallbladder with painless jaundice is unlikely to be gallstones -think cancer of the pancreatic head or distal bile duct.
Position -retroperitoneal (except the tail), behind the stomach at about L1–L2: head in the curve of the duodenum, uncinate process behind the superior mesenteric vessels, neck over the portal vein, body across the aorta, tail at the splenic hilum.
Pancreatic pain radiates to the back and is eased by sitting forward.
Exocrine function -about 1.5 L a day of juice:
Bicarbonate (from duct cells, stimulated by secretin) neutralises stomach acid.
Enzymes (from acinar cells, stimulated by CCK) -lipase, amylase, and proteases made as inactive precursors (trypsinogen is activated by enteropeptidase in the duodenum; trypsin then activates the others).
Acute pancreatitis -enzymes activated too early inside the pancreas → self-digestion; main causes are gallstones and alcohol (also high triglycerides, high calcium, drugs, ERCP, trauma).
Exocrine insufficiency -appears when about 90% of function is lost -fatty, pale, floating stools (steatorrhoea), weight loss, fat-soluble vitamin deficiency; measure faecal elastase. Causes -chronic pancreatitis, cancer, cystic fibrosis, pancreatic surgery.
Endocrine function -the islets (insulin, glucagon) -covered in the Endocrine Anatomy, Physiology and Pharmacology chapter.
Pancreatic cancer in the head blocks the bile duct early (painless jaundice); in the body and tail it presents late (back pain, weight loss, new diabetes).
Peritoneum -two layers: parietal (lines the abdominal wall -sharp, well-localised pain) and visceral (covers organs -dull, poorly localised pain). The space between normally holds a little fluid; excess fluid is ascites.
Peritonitis -inflamed parietal peritoneum: guarding, rigidity, rebound tenderness, lying still; from a perforation (free gas under the diaphragm on erect chest X-ray) or infection.
Retroperitoneal organs ("SAD PUCKER") -suprarenal (adrenal) glands, aorta and IVC, duodenum (most), pancreas (most), ureters, colon (ascending and descending), kidneys, oesophagus, rectum. Retroperitoneal bleeding may show as flank bruising (Grey Turner's sign).
Greater omentum -hangs from the stomach; walls off infection ("the abdominal policeman"); site of cancer deposits ("omental cake").
Lesser sac -behind the stomach; fluid collects here in pancreatitis (pseudocysts).
Nine regions -right and left hypochondrium, epigastrium, right and left lumbar (flank), umbilical, right and left iliac fossa, suprapubic (hypogastrium) -used to describe where pain or masses are.
Inguinal canal -indirect hernias pass through the deep ring (lateral to the inferior epigastric vessels); direct hernias push through the posterior wall (Hesselbach's triangle, medial to the vessels); femoral hernias (below and lateral to the pubic tubercle) are most likely to strangulate.
Oral (voluntary) -chewing, forming a bolus, pushing it back with the tongue.
Pharyngeal (reflex, under 1 second) -soft palate closes the nose, larynx rises and the epiglottis covers the airway, breathing stops briefly, the upper oesophageal sphincter opens. Controlled by the brainstem (cranial nerves V, VII, IX, X, XII).
Oesophageal -peristalsis carries the bolus down; the lower oesophageal sphincter relaxes.
Oropharyngeal dysphagia (difficulty starting a swallow, coughing, choking, nasal regurgitation) -stroke, Parkinson's, motor neurone disease, myasthenia, dementia -risk of aspiration pneumonia; speech and language therapy assessment.
Oesophageal dysphagia (food sticks after swallowing):
Solids then liquids, progressive -a stricture or cancer (urgent endoscopy).
Solids and liquids from the start -a motility problem (achalasia -failure of the lower sphincter to relax; spasm).
Food bolus impaction in a young man with atopy -eosinophilic oesophagitis.
Tablets and swallowing -some drugs cause pill oesophagitis if they stick (doxycycline, bisphosphonates, potassium, iron, NSAIDs) -take with plenty of water while upright.
Phases -cephalic (sight and smell of food -vagus), gastric (food in the stomach -about two-thirds of acid), intestinal.
Inhibition -somatostatin, low stomach pH (negative feedback on gastrin), fat and acid in the duodenum.
Acid's jobs -kills microbes, activates pepsin, helps absorb iron, B12 (releases it from food) and calcium. Low acid (PPIs, atrophic gastritis) → infections (C. difficile, Salmonella), bacterial overgrowth, poor iron and B12 absorption; high gastrin.
Mucosal protection -mucus and bicarbonate layer, tight cell junctions, rapid cell renewal, good blood flow, and prostaglandins (made by COX-1 -they increase mucus, bicarbonate and blood flow).
Why NSAIDs cause ulcers -they block COX-1, so protective prostaglandins fall; aspirin also damages cells directly and stops platelets working (more bleeding).
Helicobacter pylori -a spiral bacterium that survives acid by making urease (turns urea into ammonia -the basis of the urea breath test); causes gastritis, duodenal and gastric ulcers, gastric cancer and MALT lymphoma.
Zollinger–Ellison syndrome -a gastrin-secreting tumour (gastrinoma, sometimes with MEN 1) → multiple or unusual ulcers, diarrhoea; very high gastrin off PPIs.
Salivary and pancreatic amylase break starch into sugars; brush border enzymes (lactase, sucrase, maltase) finish the job.
Glucose and galactose are absorbed with sodium by SGLT1 -the reason oral rehydration solution contains both sugar and salt (glucose pulls sodium and water in, even in cholera).
Fructose is absorbed by a separate carrier (GLUT5) -limited capacity (fructose and sorbitol cause diarrhoea in large amounts).
Lactase deficiency (common worldwide; after gastroenteritis or coeliac disease) -undigested lactose → bloating, wind and diarrhoea.
Proteins -pepsin (stomach), then trypsin, chymotrypsin and others (pancreas), then brush border peptidases; absorbed as amino acids and small peptides.
Fats:
Bile acids emulsify fat into small droplets; pancreatic lipase breaks triglycerides into fatty acids and monoglycerides.
These form micelles with bile acids and are absorbed in the jejunum.
Inside cells, fats are rebuilt and packaged into chylomicrons, which enter the lymphatics (lacteals) -not the portal vein.
Fat malabsorption (no bile, no lipase, damaged lining) → steatorrhoea and deficiency of the fat-soluble vitamins A, D, E and K (bruising and raised INR from vitamin K deficiency).
Malabsorption -think where:
Lumen -no bile (cholestasis), no enzymes (pancreatic insufficiency), bacterial overgrowth.
Lining -coeliac disease, Crohn's, infections (Giardia), radiation enteritis, short bowel.
After the lining -lymphatic blockage (lymphangiectasia, lymphoma).
Absorbed as ferrous (Fe2+) iron -helped by acid and vitamin C, reduced by PPIs, tea and calcium. Controlled by hepcidin (made by the liver -blocks iron release from gut cells); inflammation raises hepcidin (anaemia of chronic disease). Oral iron raises hepcidin for about a day, so alternate-day dosing can improve absorption and tolerance.
Vitamin B12
Terminal ileum
Released from food by acid, bound to intrinsic factor (from parietal cells), absorbed in the terminal ileum. Body stores last 3–5 years. Deficiency -pernicious anaemia, gastrectomy, ileal disease or resection, bacterial overgrowth, metformin, long-term PPIs, vegan diet.
Folate
Jejunum
Stores last only about 4 months. Deficiency -poor diet, alcohol, coeliac disease, pregnancy, haemolysis, drugs (methotrexate, trimethoprim, phenytoin, sulfasalazine).
Calcium
Duodenum (active, needs vitamin D)
Reduced in coeliac disease, vitamin D deficiency, fat malabsorption.
Fat-soluble vitamins (A, D, E, K)
Small bowel, with fat
Lost in fat malabsorption; vitamin K deficiency raises INR (corrects with IV vitamin K if cholestatic, not if the liver can't make clotting factors).
Bile acids
Terminal ileum
Loss causes bile acid diarrhoea and, if large, fat malabsorption.
Thiamine (B1)
Jejunum
Low stores (weeks); deficient in alcohol excess, vomiting, malnutrition -Wernicke's encephalopathy; give before glucose in at-risk patients.
Refeeding syndrome -on restarting feeding after starvation, insulin drives phosphate, potassium and magnesium into cells → dangerous low levels (heart failure, arrhythmias, weakness); start feeding slowly and replace electrolytes and thiamine (NICE CG32).
Daily fluid traffic -about 2 L drunk plus about 7 L secreted (saliva, gastric juice, bile, pancreatic juice, intestinal juice) = about 8–9 L entering the small bowel; the small bowel absorbs about 7 L and the colon about 1–1.5 L; only about 100–200 mL leaves in stool.
Electrolytes in GI losses:
Vomiting or NG drainage -loss of acid and chloride → metabolic alkalosis, low chloride, low potassium (mostly from kidney losses driven by aldosterone).
Diarrhoea -loss of bicarbonate and potassium → metabolic acidosis (normal anion gap), low potassium.
High-output stomas and fistulas -sodium and magnesium loss, dehydration, AKI.
Villous adenoma of the rectum -potassium-rich mucus (low potassium).
Types of diarrhoea:
Osmotic -unabsorbed substances pull water in (lactose intolerance, magnesium, lactulose, sorbitol, malabsorption) -stops when fasting; raised stool osmotic gap.
Secretory -the gut actively secretes chloride and water (cholera toxin raises cAMP and opens CFTR chloride channels; VIPoma, carcinoid, bile acids, laxative misuse) -continues when fasting; large volume.
Inflammatory -blood, pus, fever (IBD, Shigella, Campylobacter, C. difficile).
Peristalsis -co-ordinated contraction behind and relaxation in front of the bolus (enteric reflex).
Gastric emptying -liquids empty quickly; solids are ground first (about 2–4 hours); fat, acid and high calorie meals slow emptying. Gastroparesis (diabetes, opioids, GLP-1 agonists, after surgery) -early fullness, vomiting of old food.
Migrating motor complex -"housekeeping" waves every 90–120 minutes between meals that sweep debris and bacteria along (driven by motilin -erythromycin is a motilin agonist, used to speed gastric emptying); loss → bacterial overgrowth.
Gastrocolic reflex -eating triggers colonic movement (urge to open the bowels after meals -used in bowel training, strong in IBS).
Defecation -rectal stretch → urge; internal sphincter relaxes (reflex); the external sphincter and puborectalis relax voluntarily; abdominal straining. Problems -constipation (slow transit, outlet obstruction -dyssynergia), faecal incontinence (sphincter damage, neurological), overflow diarrhoea from faecal impaction in older people.
Vomiting -co-ordinated by the vomiting centre in the brainstem, with inputs that explain antiemetic choice:
Chemoreceptor trigger zone (area postrema -outside the blood–brain barrier; D2, 5-HT3, NK1 receptors) -drugs, toxins, uraemia, high calcium, pregnancy.
Albumin (half-life about 3 weeks -falls slowly; also low in inflammation, nephrotic syndrome, malnutrition) -low albumin → oedema and ascites.
Clotting factors -most of them, including the vitamin K-dependent factors II, VII, IX and X. Factor VII has the shortest half-life (about 6 hours), so the INR rises within hours in acute liver failure -the best quick marker of liver function. (The liver also makes anticoagulant proteins -so patients with cirrhosis are not "auto-anticoagulated" and still get clots.)
Glucose control -stores glycogen, makes glucose (gluconeogenesis) -hypoglycaemia in acute liver failure.
Ammonia removal -the urea cycle turns ammonia from gut bacteria and protein breakdown into urea; liver failure and portosystemic shunting → high ammonia → hepatic encephalopathy. Urea is often low in liver failure.
Fat and cholesterol -makes cholesterol, lipoproteins and bile acids; fat build-up causes fatty liver (MASLD).
Bilirubin -conjugation and excretion into bile (see the next section).
Drug and hormone metabolism:
Phase 1 -oxidation by cytochrome P450 enzymes (CYP3A4, 2D6, 2C9, 2C19, 1A2) -the site of many drug interactions (inducers and inhibitors).
Phase 2 -conjugation (glucuronidation, sulfation, acetylation, glutathione) to make drugs water-soluble for excretion.
Breaks down oestrogen (gynaecomastia and spider naevi in cirrhosis), aldosterone and insulin.
Storage -glycogen, vitamins A, D and B12, iron (haemochromatosis), copper (Wilson's disease).
Immune role -Kupffer cells clear gut bacteria; liver failure → infection risk (spontaneous bacterial peritonitis, sepsis).
Signs of chronic liver disease explained -jaundice (bilirubin), bruising (clotting factors), oedema and ascites (albumin, portal pressure), confusion and flap (ammonia), spider naevi, palmar erythema and gynaecomastia (oestrogen), splenomegaly and low platelets (portal hypertension).
Old red cells are broken down → haem → unconjugated bilirubin (not water-soluble; carried on albumin; not in urine).
The liver conjugates it (enzyme UGT1A1) → conjugated bilirubin (water-soluble) → bile → gut.
Gut bacteria convert it to urobilinogen → stercobilin (makes stool brown); some urobilinogen is reabsorbed and passed in urine.
Types of jaundice:
Pre-hepatic (haemolysis, Gilbert's syndrome) -unconjugated; no bilirubin in urine; normal stool and urine colour. Gilbert's (reduced UGT1A1, about 5% of people) -mild jaundice with fasting or illness; harmless; affects irinotecan metabolism.
Hepatic (hepatitis, cirrhosis) -mixed.
Post-hepatic (obstructive) -gallstones, cancer of the pancreatic head, strictures, PSC -conjugated; dark urine, pale stools, itch (bile salts in skin); raised ALP and GGT; dilated ducts on ultrasound.
Bile -bile acids, cholesterol, phospholipids, bilirubin and bicarbonate; about 500–600 mL a day. Gallstones form when bile has too much cholesterol relative to bile acids (cholesterol stones), or too much bilirubin (pigment stones -haemolysis).
Enterohepatic circulation -about 95% of bile acids are reabsorbed in the terminal ileum and recycled to the liver several times a day.
Ileal disease or resection → bile acid diarrhoea (colon irritated by bile acids -treat with colestyramine or colesevelam); larger losses → fat malabsorption, gallstones and oxalate kidney stones.
Drugs also undergo enterohepatic recycling (e.g. some oestrogens, mycophenolate) -interrupted by antibiotics and bile acid binders.
The microbiome -trillions of bacteria, mainly in the colon: digest fibre into short-chain fatty acids, make vitamin K and some B vitamins, train the immune system, and block harmful bacteria.
Disrupted microbiome:
Antibiotics (especially clindamycin, cephalosporins, co-amoxiclav and quinolones) and PPIs → C. difficile infection.
Small intestinal bacterial overgrowth -slow motility (diabetes, scleroderma), blind loops after surgery, low acid; bloating, diarrhoea, B12 deficiency (bacteria use it) with raised folate (bacteria make it).
Bacterial translocation in cirrhosis → spontaneous bacterial peritonitis.
Faecal microbiota transplant -for recurrent C. difficile infection (NICE).
IBD -an abnormal immune response to gut bacteria in genetically susceptible people (e.g. NOD2 in Crohn's); smoking worsens Crohn's but is "protective" in UC.
Coeliac disease -an immune reaction to gluten (gliadin) in people with HLA-DQ2 or DQ8; tissue transglutaminase is the autoantigen (tTG-IgA test -check total IgA, as IgA deficiency gives false negatives; patient must be eating gluten).
Portal hypertension -raised pressure in the portal vein (hepatic venous pressure gradient over 5 mmHg; over 10 mmHg is clinically significant -varices and ascites develop; bleeding risk over 12 mmHg).
Causes -cirrhosis (most), portal vein thrombosis (pre-hepatic), Budd–Chiari syndrome and right heart failure (post-hepatic), schistosomiasis (worldwide).
Mechanism -scarred liver resists flow, plus increased blood flow into the portal system from splanchnic vasodilatation (nitric oxide) -so treatment both lowers resistance and reduces inflow (non-selective beta-blockers reduce cardiac output via beta-1 and allow splanchnic vasoconstriction via beta-2 blockade; terlipressin constricts splanchnic vessels).
How ascites forms -portal hypertension raises pressure in the sinusoids → fluid leaks; splanchnic vasodilatation lowers the effective blood volume → RAAS, sympathetic system and ADH are activated → the kidneys retain sodium and water (low urine sodium) and dilute the blood (hyponatraemia). The basis of treatment with spironolactone and salt restriction.
Hepatorenal syndrome -extreme kidney vasoconstriction from the same process → AKI without kidney damage; treated with terlipressin and albumin.
Serum–ascites albumin gradient (SAAG) -serum albumin minus ascitic albumin:
11 g/L or more -portal hypertension (cirrhosis, heart failure, Budd–Chiari).
Excretion; visible jaundice usually over about 40–50
ALT
Under about 40 U/L (varies)
Liver cell damage (hepatocellular)
AST
Under about 40 U/L
Liver, muscle, heart, red cells; AST:ALT over 2 suggests alcohol
ALP
About 30–130 U/L
Bile ducts (cholestasis), bone, placenta, growing children
GGT
Under about 50 U/L
Confirms a liver source of ALP; raised by alcohol and enzyme-inducing drugs
Albumin
35–50 g/L
Chronic synthetic function (also nutrition, inflammation, losses)
Prothrombin time / INR
INR about 0.8–1.2
Acute synthetic function (and vitamin K status)
Platelets
150–400 × 10⁹/L
Low in portal hypertension (splenic pooling)
Amylase / lipase
Lab-specific
Over 3 times the upper limit supports acute pancreatitis
Faecal calprotectin
Under about 50 micrograms/g
Gut inflammation -helps separate IBD from IBS
Ascitic neutrophils
Under 250 cells/mm³
Over 250 -spontaneous bacterial peritonitis
Hepatitic pattern (ALT up much more than ALP) -viral hepatitis, drugs, alcohol, MASLD, autoimmune hepatitis, haemochromatosis, Wilson's. ALT in the thousands -paracetamol, ischaemic hepatitis, acute viral hepatitis, (briefly) a passed gallstone.
Cholestatic pattern (ALP and GGT up more than ALT) -bile duct obstruction, PBC, PSC, drugs (co-amoxiclav, flucloxacillin), infiltration (cancer, sarcoid).
Isolated raised ALP with normal GGT -think bone (Paget's, metastases, fractures, vitamin D deficiency), pregnancy or growth.
Isolated raised bilirubin (unconjugated) with normal enzymes -Gilbert's syndrome or haemolysis.
"LFTs" that really test liver function are bilirubin, albumin and INR; the enzymes show damage, not function.
See the BSG guideline on abnormal liver blood tests for the standard liver aetiology screen.
Mechanism -irreversibly block the proton pump; activated by acid, so they work best taken 30–60 minutes before breakfast. Full effect takes a few days.
Uses -GORD and oesophagitis, peptic ulcers, H. pylori eradication, protection with NSAIDs (especially over 65, previous ulcer, with anticoagulants, steroids or SSRIs), Barrett's oesophagus, Zollinger–Ellison, after endoscopic treatment of bleeding ulcers.
Side effects -headache, diarrhoea, nausea; with long-term use: C. difficile infection, hypomagnesaemia (can cause low calcium and potassium -check magnesium if on long-term PPIs with digoxin or diuretics -MHRA), hyponatraemia, fractures, B12 deficiency, pneumonia, acute interstitial nephritis, subacute cutaneous lupus (MHRA), fundic gland polyps.
Rebound acid after stopping -taper or step down to as-needed use.
Masking cancer -PPIs can heal malignant ulcers and hide symptoms; stop 2 weeks before endoscopy or H. pylori testing.
PPI interactions:
Omeprazole and esomeprazole inhibit CYP2C19 → less activation of clopidogrel (avoid the combination -use lansoprazole or pantoprazole).
Reduced absorption of drugs needing acid -itraconazole, ketoconazole, iron, levothyroxine, some HIV drugs (atazanavir, rilpivirine -avoid).
Raise methotrexate levels at high doses.
Deprescribing -many patients stay on PPIs without a reason; review at least yearly.
H2 receptor antagonists -famotidine, nizatidine (ranitidine was withdrawn in 2020 because of an impurity, NDMA); weaker than PPIs; useful for night-time symptoms; cimetidine inhibits many CYP enzymes (interactions).
Antacids and alginates (e.g. Gaviscon) -quick symptom relief; alginates form a raft on top of stomach contents. Cautions -sodium content (heart failure, hypertension), magnesium salts cause diarrhoea and aluminium salts cause constipation; antacids reduce absorption of many drugs (separate by 2 hours -e.g. tetracyclines, quinolones, iron, levothyroxine).
Misoprostol -prostaglandin analogue that protects the stomach lining; diarrhoea; causes uterine contractions -contraindicated in pregnancy (also used in obstetrics).
Sucralfate -coats ulcers; can cause constipation, bezoars, and aluminium build-up in CKD; reduces absorption of other drugs.
Who to test -dyspepsia without alarm features (test and treat), peptic ulcer, MALT lymphoma, before long-term aspirin or NSAIDs in high-risk people, unexplained iron deficiency, ITP.
Tests -urea breath test or stool antigen test; stop PPIs for 2 weeks and antibiotics for 4 weeks before testing (false negatives). Serology can't show cure.
Choose the antibiotic the patient has not had recently (resistance -especially to clarithromycin); bismuth-based quadruple therapy and levofloxacin regimens are used for second-line or resistant cases (local guidance).
Side effects to warn about -diarrhoea and C. difficile, taste disturbance; metronidazole with alcohol (disulfiram-like reaction -flushing, vomiting); clarithromycin -QT prolongation and CYP3A4 interactions (statins -pause simvastatin; warfarin; colchicine).
Adherence is the main reason for failure -complete the full course.
Retest (urea breath test at least 4 weeks after treatment) -after gastric ulcer, MALT lymphoma, or if symptoms persist; repeat endoscopy for gastric ulcers to confirm healing (and exclude cancer).
Extrapyramidal effects -acute dystonia (young women), tardive dyskinesia; maximum 5 days, 10 mg up to 3 times a day (MHRA); avoid in Parkinson's, bowel obstruction, under 1 year
Domperidone
Peripheral D2 antagonist (doesn't cross the blood–brain barrier)
Nausea in Parkinson's (e.g. with dopaminergic drugs), gastroparesis
QT prolongation and sudden cardiac death -lowest dose, shortest time (usually up to 7 days), avoid with QT-prolonging drugs and CYP3A4 inhibitors and in cardiac disease (MHRA)
Drowsiness, dry mouth; can worsen heart failure; misuse potential (IV)
Prochlorperazine
D2 antagonist (phenothiazine)
Vertigo, labyrinthitis, migraine, pregnancy
Extrapyramidal effects, drowsiness, postural hypotension; avoid in Parkinson's
Haloperidol (low dose)
D2 antagonist
Chemical causes (drugs, renal failure, high calcium) -palliative care
Extrapyramidal effects, QT; avoid in Parkinson's and Lewy body dementia
Levomepromazine
Broad (D2, 5-HT2, H1, alpha)
Palliative care when others fail
Sedation, hypotension
Hyoscine (hydrobromide patch or butylbromide)
Antimuscarinic
Motion sickness (hydrobromide); colic and secretions in bowel obstruction (butylbromide)
Dry mouth, confusion in older people (hydrobromide), urinary retention, glaucoma
Aprepitant
NK1 antagonist
Chemotherapy (with ondansetron and dexamethasone)
CYP3A4 interactions (reduces the effect of the pill and warfarin)
Dexamethasone
Corticosteroid
Chemotherapy; raised intracranial pressure; palliative care
Hyperglycaemia, insomnia (give in the morning)
Choose by cause -find and treat the cause (drugs, constipation, high calcium, infection, raised pressure, obstruction) as well as the symptom.
Acute dystonic reactions (oculogyric crisis, torticollis) -stop the drug; give procyclidine (IV or IM).
Bowel obstruction -avoid prokinetics (metoclopramide, domperidone) in complete obstruction; use cyclizine, haloperidol or hyoscine butylbromide.
Pregnancy (nausea and hyperemesis, RCOG) -first-line antihistamines (cyclizine, promethazine) or phenothiazines (prochlorperazine), then metoclopramide or ondansetron; check for Wernicke's risk (thiamine) and dehydration.
Cramps; work in 6–12 hours (orally); avoid in obstruction; add to macrogol for opioid constipation
Softeners
Docusate, arachis oil enema
Soften stool (docusate is also a weak stimulant)
Arachis oil contains peanut oil -avoid in peanut allergy
Opioid receptor antagonists (peripheral)
Naloxegol, methylnaltrexone, naldemedine
Block gut opioid receptors without reversing pain relief
For opioid-induced constipation not responding to laxatives; avoid in obstruction
Prokinetic / secretagogue
Prucalopride (5-HT4 agonist), linaclotide
Increase colonic movement or fluid secretion
Chronic constipation and IBS with constipation not helped by other laxatives (specialist or after 6–12 months)
Opioid-induced constipation -start a stimulant plus a softener or osmotic laxative when starting regular opioids (avoid bulk-forming).
Red flags before treating constipation -weight loss, rectal bleeding, change in bowel habit over 60, iron deficiency anaemia, abdominal or rectal mass -consider cancer (NICE NG12).
Bowel preparation (e.g. Moviprep, Picolax, Plenvu) -risk of dehydration, AKI, hyponatraemia and hypokalaemia (frail, CKD, heart failure, diuretics) -hold diuretics and ACE inhibitors, check U&E in high-risk people; phosphate-based preparations can cause kidney damage.
Oral rehydration solution -the most important treatment for acute diarrhoea.
Loperamide -peripheral opioid agonist (doesn't enter the brain at normal doses); slows the gut and increases water absorption.
Avoid in bloody diarrhoea, fever, suspected C. difficile, and acute flares of IBD (risk of toxic megacolon).
High doses (misuse) cause QT prolongation and serious arrhythmias (MHRA).
Useful in high-output stomas (higher specialist doses, taken before meals), chronic diarrhoea in IBS.
Codeine phosphate -also slows the gut (high-output stomas); dependence and sedation.
Bile acid sequestrants -colestyramine, colesevelam, colestipol -bind bile acids (bile acid diarrhoea, itch in cholestasis); bind other drugs (levothyroxine, warfarin, digoxin, fat-soluble vitamins -take other drugs at least 1 hour before or 4–6 hours after); constipation, bloating.
Antispasmodics -mebeverine, alverine, peppermint oil (can worsen reflux), hyoscine butylbromide (Buscopan -antimuscarinic; IM or IV injection can cause serious tachycardia and hypotension in patients with heart disease -MHRA).
Laxatives for IBS with constipation (avoid lactulose -causes bloating); linaclotide if others fail.
Loperamide for IBS with diarrhoea.
Low-dose tricyclic antidepressants (amitriptyline 5–10 mg at night, increased slowly) as second-line for pain -act as gut "neuromodulators"; SSRIs if TCAs don't help.
Diet (regular meals, fibre adjustment, low FODMAP with a dietitian), psychological therapies.
C. difficile treatment -stop the causing antibiotic and PPIs if possible; oral vancomycin first-line (fidaxomicin for recurrence or high risk of recurrence -NICE NG199); avoid antidiarrhoeals.
IBD Drugs -Aminosalicylates, Steroids and Immunomodulators
5-aminosalicylates (5-ASA) -mesalazine (oral and rectal), sulfasalazine, olsalazine, balsalazide:
Uses -induce and maintain remission in mild to moderate ulcerative colitis (rectal treatment for proctitis -often better than oral); little benefit in Crohn's.
Side effects -headache, diarrhoea, rash; interstitial nephritis (check U&E before starting, then periodically); blood disorders (warn about unexplained bleeding, bruising, sore throat, fever -FBC); pancreatitis; rarely myocarditis and pericarditis.
Sulfasalazine -also orange urine and tears, reversible male infertility (low sperm count), folate deficiency, rash, hepatitis; avoid with sulfonamide allergy.
Brands of oral mesalazine are not interchangeable (prescribe by brand).
Corticosteroids -for flares only, never for maintenance:
Prednisolone 40 mg daily tapering over about 8 weeks (moderate flares).
IV hydrocortisone 100 mg four times daily (or IV methylprednisolone) in acute severe ulcerative colitis (Truelove and Witts criteria) -with VTE prophylaxis, stool cultures and C. difficile test; review on day 3 for rescue therapy (ciclosporin or infliximab) or surgery.
Two or more steroid courses a year, or steroid dependence, means escalation is needed (immunomodulator or biologic); bone protection; screen for TB and diabetes risk.
Thiopurines -azathioprine (converted to 6-mercaptopurine) and mercaptopurine:
Uses -maintain remission and reduce steroid use in Crohn's and UC; take about 3 months to work.
Check TPMT (and NUDT15 where available) before starting -low activity causes life-threatening marrow suppression.
Side effects -marrow suppression, pancreatitis (usually in the first weeks), hepatitis, nausea, flu-like illness; infections; long term -non-melanoma skin cancer (sun protection and skin checks) and lymphoma (rare hepatosplenic T-cell lymphoma in young men, especially with anti-TNF).
Monitoring -FBC and LFTs weekly at first, then every 3 months; metabolite levels can guide dosing.
Allopurinol blocks xanthine oxidase, which breaks down thiopurines → dangerous toxicity -avoid, or use only with a specialist dose reduction (about a quarter of the dose).
Avoid live vaccines; check varicella immunity before starting.
Methotrexate (weekly, oral or subcutaneous) -mainly Crohn's; folic acid on another day; FBC, LFTs and U&E monitoring; teratogenic (effective contraception, for men and women); pneumonitis; avoid trimethoprim and co-trimoxazole (marrow suppression); "once weekly" prescribing errors are a known cause of death.
Ciclosporin (IV rescue in acute severe UC) -hypertension, kidney toxicity, tremor, infections; seizures if magnesium or cholesterol are low; check levels.
Crohn's and UC; generally well tolerated; IV induction then SC maintenance
Tofacitinib, upadacitinib, filgotinib
JAK inhibitors (oral)
Fast acting; MHRA -increased risk of VTE, major cardiovascular events, cancer and serious infection: avoid in people over 65, smokers and those with cardiovascular or cancer risk unless no alternative; shingles (vaccinate); raised lipids; teratogenic
Ozanimod, etrasimod
S1P receptor modulators (oral -keep lymphocytes in lymph nodes)
Before starting any biologic or small molecule -screen for TB (IGRA and chest X-ray), hepatitis B and C, HIV, varicella immunity; update vaccinations (pneumococcal, flu, COVID-19, shingles -non-live vaccine); no live vaccines while on treatment (and for infants exposed to biologics in late pregnancy, usually for the first 6–12 months -specialist advice).
Hepatitis B reactivation -risk with steroids, biologics, rituximab and chemotherapy -check HBsAg and anti-HBc first; antiviral prophylaxis if positive.
Pregnancy -most IBD drugs (5-ASA, thiopurines, anti-TNF) are continued because active disease is riskier for the baby; methotrexate, JAK inhibitors and S1P modulators are not.
Biosimilars -cheaper versions of infliximab and adalimumab; switching is usually safe.
Lactulose -first-line for hepatic encephalopathy: osmotic laxative that also acidifies the colon, trapping ammonia as ammonium (not absorbed) and reducing ammonia-making bacteria; aim for 2–3 soft stools a day (avoid dehydration and low sodium from over-use). Phosphate enemas if unable to take orally.
Rifaximin -poorly absorbed antibiotic; added to lactulose to prevent recurrent hepatic encephalopathy (NICE TA337).
Non-selective beta-blockers -carvedilol (preferred in BSG guidance) or propranolol -lower portal pressure; for primary prevention of variceal bleeding (medium or large varices) and, with banding, secondary prevention. Hold or reduce if systolic BP is under 90, AKI, sepsis or SBP, and use with care in refractory ascites.
Uses -acute variceal bleeding (with antibiotics and endoscopy) and hepatorenal syndrome (with albumin).
Side effects -ischaemia (heart, gut, fingers, skin), abdominal cramps and diarrhoea, hyponatraemia, bradycardia; respiratory failure from fluid overload -MHRA: risk of serious or fatal respiratory failure -avoid in advanced liver failure and severe kidney impairment, and monitor fluid balance and oxygen.
Avoid in ischaemic heart disease and peripheral vascular disease.
Antibiotics in variceal bleeding -prophylactic IV antibiotics (per local policy) reduce infection, rebleeding and death in all cirrhotic patients with GI bleeding.
Diuretics for ascites:
Spironolactone first-line (100 mg rising to 400 mg) -blocks the raised aldosterone; side effects -hyperkalaemia, hyponatraemia, painful gynaecomastia (amiloride is an alternative), AKI.
Add furosemide if needed (low potassium, AKI); aim for weight loss of about 0.5 kg a day (1 kg a day if there is oedema).
Stop diuretics with sodium under 120–125, AKI, or encephalopathy.
Human albumin solution (20%):
After large-volume paracentesis (more than 5 L) -about 8 g albumin per litre drained (100 mL of 20% albumin per 2.5–3 L), to prevent circulatory dysfunction and AKI.
SBP -albumin on day 1 and day 3 with antibiotics reduces kidney failure and death.
Hepatorenal syndrome -with terlipressin.
SBP -treat with IV antibiotics (e.g. cefotaxime or per local policy); prophylaxis after an episode (ciprofloxacin or co-trimoxazole) and in some high-risk patients.
Vitamin K (IV phytomenadione) -corrects a raised INR from vitamin K deficiency (cholestasis, malnutrition, antibiotics); won't correct INR from synthetic failure.
Ursodeoxycholic acid -a bile acid that improves bile flow; first-line for primary biliary cholangitis (13–15 mg/kg/day -improves survival); second-line PBC drugs (e.g. PPAR agonists such as elafibranor or seladelpar) are specialist.
Itch in cholestasis -colestyramine first-line, then rifampicin (watch LFTs), naltrexone, sertraline.
Autoimmune hepatitis -prednisolone (or budesonide) plus azathioprine.
Viral hepatitis:
Hepatitis C -direct-acting antivirals (e.g. sofosbuvir-based combinations, glecaprevir–pibrentasvir) for 8–12 weeks cure over 95%; check interactions (sofosbuvir with amiodarone -severe bradycardia; enzyme inducers; PPIs with some regimens) and check for hepatitis B (reactivation risk).
Hepatitis B -tenofovir or entecavir (suppress, rarely cure); monitor kidney function and bone with tenofovir disoproxil.
Wilson's disease -copper chelation (penicillamine, trientine) and zinc; haemochromatosis -venesection.
Thiamine -IV Pabrinex for suspected Wernicke's encephalopathy (confusion, ataxia, eye signs -often incomplete) or high-risk patients (e.g. malnourished, vomiting, withdrawing); oral thiamine for prevention. Give before or with glucose. Rare anaphylaxis -have resuscitation available.
Alcohol withdrawal (NICE CG100):
Chlordiazepoxide in a reducing regimen, guided by symptom scores (e.g. CIWA-Ar) -prevents withdrawal seizures and delirium tremens.
In significant liver impairment, lorazepam or oxazepam (short-acting, not dependent on liver oxidation) -avoid oversedation, which can mimic or precipitate encephalopathy.
Withdrawal seizures -lorazepam; delirium tremens -benzodiazepines, ITU if severe.
Severe alcohol-related hepatitis -prednisolone 40 mg daily for 28 days may be considered if the discriminant function is 32 or more (only modest short-term benefit -STOPAH trial); stop at day 7 if the Lille score shows no response; exclude infection and GI bleeding first. Nutrition is crucial.
Relapse prevention (after withdrawal, with psychosocial support):
Acamprosate -reduces craving (glutamate/GABA effects); avoid in severe kidney impairment; diarrhoea.
Naltrexone -opioid antagonist; reduces the reward of drinking; avoid with opioids (withdrawal, blocks pain relief) and in acute hepatitis or liver failure.
Disulfiram -blocks aldehyde dehydrogenase → acetaldehyde build-up with any alcohol (flushing, vomiting, palpitations, hypotension -can be dangerous); avoid in heart disease, psychosis, pregnancy; warn about hidden alcohol in foods and toiletries.
Baclofen is sometimes used by specialists in liver disease (off-label).
Take with every meal and snack (dose in lipase units -e.g. about 50,000 units with meals and 25,000 with snacks in adults, then adjusted); swallow whole; don't chew.
Adding a PPI can help (protects enzymes from acid).
Made from pork -discuss with patients for whom this matters.
Side effects -abdominal discomfort, constipation; fibrosing colonopathy with very high doses in cystic fibrosis.
Under-used in pancreatic cancer -offer to anyone with suspected malabsorption (NICE NG85).
Fat-soluble vitamin supplements (A, D, E, K) in fat malabsorption.
Bile acid sequestrants -see Antidiarrhoeals and IBS Drugs.
Ursodeoxycholic acid -also used to dissolve small cholesterol gallstones (rarely; slow and stones recur) and to prevent stones after rapid weight loss.
Acute pancreatitis -no drug alters its course; treatment is fluids (avoid over-resuscitation), pain relief (opioids are fine), nutrition (enteral, early), antibiotics only for proven infection, and treating the cause (ERCP for cholangitis, cholecystectomy for gallstones).
Why it's difficult -there's no simple marker like eGFR; use the clinical picture (Child–Pugh score -bilirubin, albumin, INR, ascites, encephalopathy) and the BNF.
Changes in cirrhosis:
Less first-pass metabolism (portosystemic shunting) → higher levels of oral drugs normally cleared by the liver (morphine, propranolol, many others) -start low.
Slower drug metabolism (fewer working cells) → longer half-lives (benzodiazepines like diazepam -prefer lorazepam or oxazepam).
Low albumin → more free drug (phenytoin, warfarin).
Ascites → larger volume for water-soluble drugs (e.g. some antibiotics).
Drugs to avoid or use with great care:
Sedatives, opioids and constipating drugs -precipitate hepatic encephalopathy (if needed, use small doses, avoid codeine and long-acting drugs, give laxatives).
NSAIDs -GI bleeding, kidney failure (hepatorenal syndrome) and fluid retention -avoid in cirrhosis.
ACE inhibitors, ARBs and aminoglycosides -AKI in ascites.
Anticoagulants and antiplatelets -bleeding risk (especially with varices and low platelets) -but anticoagulation is still used when needed (portal vein thrombosis, AF) with specialist advice.
Drugs that cause fluid retention -NSAIDs, steroids, high-sodium preparations (some effervescent and IV antibiotics).
Hepatotoxic drugs -methotrexate, high-dose paracetamol in malnourished patients.
PPIs -increased risk of SBP and encephalopathy in cirrhosis -use only with a clear reason.
Paracetamol -the preferred painkiller in liver disease at a reduced dose (e.g. maximum 2–3 g a day in cirrhosis, low weight, malnutrition or alcohol excess) -safer than NSAIDs or opioids.
Statins are safe in stable chronic liver disease and MASLD (avoid in decompensated cirrhosis).
Co-amoxiclav (may start up to 6 weeks after the course), flucloxacillin (older people; may be delayed), chlorpromazine, combined pill, anabolic steroids, carbimazole, sulfonylureas, erythromycin, terbinafine
Management -stop the suspected drug (most recover); check timing (most occur within 3 months of starting); exclude other causes; report on the Yellow Card scheme; never rechallenge after severe injury. LiverTox is a useful resource.
Hy's law -drug-induced hepatocellular injury with jaundice carries about a 10% risk of death or transplant -urgent specialist referral.
Paracetamol overdose:
Normally conjugated safely; in overdose, more is turned into the toxic metabolite NAPQI (by CYP2E1) and glutathione runs out → zone 3 necrosis.
Acetylcysteine replenishes glutathione -use the UK treatment nomogram (treatment line from 100 mg/L at 4 hours); treat without waiting for levels if staggered, uncertain timing or presenting late; follow the current UK regimen and TOXBASE. Reactions (rash, wheeze) are usually histamine-like, not true allergy -pause and give an antihistamine.
Poor prognosis markers (King's College criteria for transplant referral) -pH under 7.3 after resuscitation, or INR over 6.5, creatinine over 300 and grade 3–4 encephalopathy together; rising lactate.
1. A 58-year-old man with alcohol-related cirrhosis vomits 500 mL of fresh blood. HR 118, BP 92/58, Hb 78. Answer: Suspected acute variceal bleeding.
Resuscitate -large-bore access, fluids, restrictive transfusion (target Hb about 70–80 g/L -over-transfusion raises portal pressure); correct platelets only if very low and actively bleeding.
Terlipressin and IV antibiotics before endoscopy; urgent endoscopy after resuscitation with band ligation; Pabrinex.
Stop beta-blockers and diuretics during the bleed; afterwards -carvedilol or propranolol plus repeat banding; consider TIPS if bleeding is uncontrolled.
2. A 68-year-old woman with a recent coronary stent takes aspirin, clopidogrel, omeprazole and ibuprofen for knee pain. She is admitted with melaena. Answer: Upper GI bleed from NSAID-related ulceration, with a CYP2C19 interaction risk.
Glasgow–Blatchford score, resuscitation, endoscopy within 24 hours; high-dose PPI after endoscopic treatment.
Stop ibuprofen; discuss antiplatelets with cardiology (don't stop both without advice -stent thrombosis risk).
Switch omeprazole to lansoprazole or pantoprazole; test for H. pylori and treat if positive.
3. A 34-year-old man with Crohn's disease starts azathioprine. Six weeks later he has a sore throat and fever. He also takes allopurinol for gout, started by his GP last month. Answer: Likely thiopurine-induced marrow suppression (neutropenic sepsis), worsened by allopurinol.
Urgent FBC; treat as neutropenic sepsis if neutrophils are low -IV antibiotics within 1 hour.
Stop azathioprine and review allopurinol; check TPMT result and thiopurine metabolites.
Combining a thiopurine with allopurinol needs specialist dose reduction and close monitoring.
4. A 22-year-old woman is given IV metoclopramide for vomiting. An hour later her eyes deviate upwards and her neck twists to one side. Answer: Acute dystonic reaction (oculogyric crisis).
Stop metoclopramide; give procyclidine 5–10 mg IV or IM (or benzatropine).
Young women and children are at highest risk; record as an adverse reaction.
Choose a different antiemetic (e.g. cyclizine or ondansetron).
5. A 65-year-old man with cirrhosis and ascites becomes drowsy and confused 3 days after admission. He has been given codeine for back pain and has not opened his bowels. He has a flapping tremor. Answer: Hepatic encephalopathy precipitated by opioid and constipation.
Stop codeine; lactulose (aim for 2–3 soft stools a day), phosphate enema if needed; rifaximin to prevent recurrence.
Look for other precipitants -diagnostic ascitic tap (SBP), GI bleeding, infection, low sodium or potassium, dehydration, diuretics, hypoglycaemia; consider a CT head if he has fallen.
Use paracetamol at a reduced dose for pain; avoid NSAIDs and sedatives.