mechanism of action of drugs

• irinotecan

  A topoisomerase inhibitor. Inhibits Topoisomerase I which relaxes supercoiled DNA for replication and reattaches broken DNA strands. Prodrug Irinotecan is hydrolysed to drug SN-38 by carboxylesterase in the liver which binds to topoisomerase 1 and fails to reattach broken strands, causing DNA damage and cell death.
• lansoprazole and omeprazole

  Inhibits gastric secretion via irreversibly binding to H+/K+ ATPase on the luminal membrane of gastric parietal cells in the stomach. A prodrug which undergoes a chemical reaction to form an active form in an acidic environment.
• Cimetidine, Ranitidine


  H2 receptor antagonist - block the action of histamine at the H2 receptors on gastric parietal cells. So reduces production of acid. Competitive antagonist.
• bulk laxatives: methylcellulose/fybogel 


  Increases faecal mass through binding/absorbing water and so helps stretch the walls of the intestine as the volume of stool increases. This stimulates peristalsis.
• stimulant laxatives: Senna/Biscodyl


  After metabolism in the colon, it stimulates mucosa of the large intestine which increases the motility of the large intestine (increase in peristalsis)
• osmotic laxatives: lactulose/magnesium hydroxide


  Act within the lumen of the large intestine to retain water via osmosis. They're not well-absorbed so lowers the water potential which increases water content in stool making it easier to pass.
• loperamide


  a mu-opioid receptor agonist. Acts on opiate receptors on the intestinal muscles (gut lining). Reduces the action of peristalsis and increases the transit time and the reabsorption of water. Reduces motility.
• capecitabine and 5-FU


  Capecitabine -> 5-DFCR (by hepatic carboxylesterase) -> 5-DFUR (by cytidine deaminase) -> 5-FU (by thymidine phosphorylase). 5-FU enters cells uncharged and then is converted to FdUMP and FUTP. FdUMP inhibits the enzyme thymidylate synthase and so blocks the synthesis of thymidine components for DNA.
• loop diuretics; furosemide, torsemide and bumetamide

  Act on thick ascending limb, inhibiting Na+/K+/2Cl- ATPase on the apical membrane. Increase excretion of sodium, chloride and potassium and so increase urine output.
• Thiazides and related diuretics; Indapamide

  Act on distal tubule. Blocks Na+/Cl- ATPase (transporter not co-transporter). Increases excretion of sodium, chloride and potassium.
• Indapamide


  Acts on DCT. Inhibits Na+/Cl- ATPase. Increase excretion of Na, Cl, K and water in urine. K loss due to sodium exchange in the collecting duct. A higher volume of fluid is lost causing a decrease in plasma volume. Lower volume = reduced venous return and reduced cardiac output. Lowering blood pressure. Also, relaxes arterioles by activating K channels in smooth muscle and providing a dilatory effect.
• ACE inhibitors; ramipril, captopril

  Competitive inhibitor of ACE (which converts angiotensin I to angiotensin II). Reduces production of angiotensin II which helps relax blood vessels, decrease blood volume and lower blood pressure. Can also help improve heart pumping ability.