Pharmacology

Question 1

Magnesium trisilicate, aluminium/magnesium mixtures (Maalox), alginates

Answer 1

Class: antacids and alginates.
MOA: increases pH of gastric acid via neutralisation reaction.
Indication: dyspepsia, GORD.
Side effects/contraindications: diarrhoea, nephrolithiasis.

Question 2

Ranitidine

Answer 2

Class: H2 receptor antagonist.
MOA: block H2 histamine receptors, reducing gastric acid secretion.
Indication: dyspepsia, GORD, peptic ulcer, prophylaxis of NASID associated peptic ulceration.
Side effects/contraindications: generally well tolerated with few side effects. Diarrhoea, headache and dizziness. Warning - they disguise the symptoms of gastro-oesophageal cancer, so important to investigate cause. Dose reduced in renal impairment.

Question 3

Lansoprazole, omeprazole, pantoprazole

Answer 3

Class: proton pump inhibitors (PPIs).
MOA: irreversibly inhibiting H+/K+ ATPase in gastric parietal cells, reducing gastric acid secretion. Suppress gastric acid secretion almost completely (unlike H2 antagonists).
Indication: peptic ulcers, prophylaxis of NSAID associated peptic ulcers, dyspepsia, GORD, eradication of H.pylori infection (in combination with antibiotics), oesophagitis.
Side effects/contraindications: GI disturbance, headache, increased risk of C.difficile infection. Prolonged treatment - hypomagnesaemia. Warning - disguise symptoms of gastro-oesophageal cancer, so important to investigate cause (e.g. weight loss, dysphagia). Increase risk of fracture in elderly. Omeprazole may interact with clopidogrel.

Question 4

Codeine phosphate

Answer 4

Class: anti-motility/anti-diarrhoea.
MOA: mu opioid receptor agonist, decreases peristalsis.
Indication: IBS, viral gastroenteritis.
Side effects/contraindications: opioid toxicity and dependence.

Question 5

Loperamide

Answer 5

Class: anti-motility/anti-diarrhoea.
MOA: mu opioid receptor agonist in the gut, reduces peristalsis, resulting in slowed transit time allowing more time for water absorption. Also increases anal sphincter tone. It has NO analgesic effects because it doesn’t penetrate CNS (so preferable over codeine).
Indication: IBS, viral gastroenteritis.
Side effects/contraindications: constipation, abdominal cramps and flatulence. Avoided in acute UC due to increased risk of megacolon and perforation. Also avoided in C.difficile colitis and acute bloody diarrhoea (dysentery).

Question 6

Diphenoxylate (co-phenotrope)

Answer 6

Class: anti-motility/anti-diarrhoea.
MOA: mu opioid receptor agonist in gut, decreasing peristalsis, increasing water absorption.
Indication: rehydration in acute diarrhoea, control of faecal consistency after colostomy or ileostomy.
Side effects/contraindications: avoid antibiotic-associated colitis.

Question 7

Kaolin

Answer 7

Class: water adsorbent/anti-diarrhoea.
MOA: adsorbs toxic molecules, binding agent.
Indication: acute diarrhoea.

Question 8

Octreotide

Answer 8

Class: somatostatin analogue.
MOA: decreases amount of water in stool.
Indication: diarrhoea associated with carcinoid tumours.

Question 9

Terlipressin

Answer 9

Class: vasopressin (ADH) analogue.
MOA: splanchnic vasoconstriction, reducing portal venous pressure.
Indication: oesophageal varices.

Question 10

Methylcellulose

Answer 10

Class: bulk-forming laxative.
MOA: increase bulk of stools, stimulating stretch receptors. Faecal softener.
Indication: constipation.
Side effects/contraindications: flatulence, bloating and cramps.

Question 11

Ispaghula husk

Answer 11

Class: bulk-forming laxative.
MOA: increases bulk of stool, stimulating stretch receptors.
Indication: constipation.
Side effects/contraindications: flatulence, bloating and cramps. Avoid in faecal impaction and intestinal obstruction.

Question 12

Senna, bisacodyl, glycerol suppositories, docusate sodium

Answer 12

Class: stimulant laxative.
MOA: increase water and electrolyte secretion, increasing volume of colonic content, stimulating peristalsis and intestinal motility. Docusate also acts as faecal softener.
Indication: constipation, faecal impaction suppositories.
Side effects/contraindications: cramps, diarrhoea. Prolonged use - melanosis coli. Avoid in intestinal obstruction (increased risk of perforation).

Question 13

Lactulose, macrogol, phosphate enema

Answer 13

Class: osmotic laxatives.
MOA: based on osmotically active substances that aren’t digested or absorbed, so they increase stool water content as water moves into bowel lumen via osmosis, stimulating peristalsis.
Indication: constipation, faecal impaction.
Side effects/contraindications: flatulence, cramps, nausea, diarrhoea. Avoid in intestinal obstruction.

Question 14

Sodium picosulphate

Answer 14

Class: stimulant laxative.
MOA: stimulates mucosa increasing intestinal motility.
Indication: constipation.
Side effects/contraindications: diarrhoea, GI discomfort. Avoid in intestinal obstruction.

Question 15

Mesalazine, sulfasalazine

Answer 15

Class: aminosalicylates.
MOA: release 5-ASA, which has anti-inflammatory and immunosuppressive effects acting topically on gut.
Indication: first line in treatment of mild-moderate UC (mesalazine).
Side effects/contraindications: GI upset (nausea, dyspepsia), headache, leukopenia, thrombocytopenia, renal impairment. Hypersensitivity reactions. Avoid in blood clotting abnormalities.

Question 16

Metoclopramide

Answer 16

Class: antiemetic.
MOA: dopamine D2 receptor antagonist in chemoreceptor trigger zone and also promotes gastric emptying.
Indication: prophylaxis and treatment of N+V.
Side effects/contraindications: diarrhoea, EPS (acute dystonia). Avoid in intestinal obstruction and perforation (pro-kinetic effects). Avoid in Parkinson’s disease.

Question 17

Cyclizine, promethazine

Answer 17

Class: antiemetic.
MOA: histamine H1 receptor antagonist, inhibiting vomiting centre in medulla. Also anti-muscarinic effects.
Indication: prophylaxis and treatment of N+V, particularly in motion sickness or vertigo.
Side effects/contraindications: drowsiness (cyclizine less sedating), dry throat and mouth, palpitations (IV injection). Avoid in hepatic encephalopathy and prostatic enlargement (urinary retention).

Question 18

Ondansetron

Answer 18

Class: antiemetic.
MOA: serotonin 5-HT3 receptor antagonist, inhibiting chemoreceptor trigger zone in vomiting centre.
Indication: prophylaxis and treatment of N+V, particularly in general anaesthesia and chemotherapy.
Side effects/contraindications: constipation. Avoided in prolonged QT interval.

Question 19

Hydrocortisone, prednisolone, budesonide

Answer 19

Class: corticosteroids.
MOA: bind cytosolic glucocorticoid receptors —> translocates to nucleus —> bind glucocorticoid-response elements —> gene expression —> up-regulate anti-inflammatory genes and down regulate pro-inflammatory genes.
Indication: suppression of IBD.
Side effects/contraindications: immuosuppression, diabetes, osteoporosis, proximal muscle weakness, skin thinning with easy bruising, mood and behavioural changes. Mineralocorticoid effects - hypertension, hypokalaemia, oedema. Prolonged treatment - adrenal atrophy. Increased risk of peptic ulcers and GI bleeding with NSAID use. Enhance hypokalaemia in patients taking beta 2 agonists, loop/thiazide diuretics.

Question 20

Azathioprine

Answer 20

Class: immunosuppressant therapy.
MOA: pro-drug. The main metabolite inhibits purine synthesis —> inhibit DNA/RNA replication —> lymphocyte suppression.
Indication: maintenance of remission in CD and UC.
Side effects/contraindications: bone marrow suppression (leukopenia), nausea, hypersensitivity reactions (diarrhoea, vomiting, rash, fever, myalgia, hypotension, pancreatitis). Rare - veno-occlusive disease, hepatotoxicity, lymphoma. TPMT phenotyping before commencing therapy. Avoided in patients with absent TPMT activity and in pregnancy. Should not be prescribed with allopurinol.

Question 21

Infliximab, adalimumab

Answer 21

Class: cytokine inhibitors (mAbs).
MOA: anti-TNF alpha —> inhibits pro-inflammatory cytokine signalling.
Indication: Crohn’s disease.
Side effects/contraindications: risk of agranulocytosis.

Question 22

Hyoscine butylbromide (Buscopan)

Answer 22

Class: anti-spasmodic/anti-muscarinic.
MOA: competitively inhibit ACh —> reduce smooth muscle tone and peristaltic contractions.
Indication: IBS.
Side effects/contraindications: tachycardia, dry mouth, constipation, urinary retention in BPH, blurred vision. Avoid in patients at risk of arrhythmias.

Question 23

Mebeverine, peppermint oil

Answer 23

Class: antispasmodics.
MOA: anticholinergic (mebeverine), relaxes GI smooth muscle by reducing calcium influx (peppermint oil).
Indication: IBS.
Side effects/contraindications: avoid mebeverine in paralytic ileus.

Question 24

Nystatin, fluconazole

Answer 24

Class: anti-fungals.
MOA: polyene antifungals (nystatin) bind ergosterol in cell membrane, creating a pore which ions leak out of —> cell death. Triazole antifungals (fluconazole) inhibit ergosterol synthesis —> inhibits cell growth and replication.
Indication: GI infections.
Side effects/contraindications: GI upset, headache, hepatitis, rash (oral fluconazole).

Question 25

Metronidazole

Answer 25

Class: anti microbial with high activity against anaerobic bacteria and protozoa.
MOA: in anaerobic bacteria, reduction of metronidazole causes DNA degradation and cell death.
Indication: antibiotic-associated colitis (C.difficile), amoebic dysentery, giardiasis.
Side effects/contraindications: N+V and rash. High dose for prolonged course - peripheral and optic neuropathy, seizures and encephalopathy. Dose reduced in patients with severe liver disease (metronidazole metabolised by CYP450). Avoid alcohol as metronidazole inhibits acetaldehyde dehydrogenase (drinking alcohol can cause disulfiram-like reaction).

Question 26

Vancomycin

Answer 26

Class: glycopeptide antibiotic.
MOA: inhibits cross-linking of peptidoglycan chains —> inhibits cell wall synthesis —> bactericidal.
Indication: antibiotic associated colitis (C.difficile).
Side effects/contraindications: thrombophlebitis at infusion site. ‘Red man syndrome’ infusion reaction if it is infused too rapidly. IV vancomycin - nephrotoxicity, ototoxicity, neutropenia and thrombocytopenia.