chemistry of drugs to treat GI inflammation

Question 1

sulfasalazine mechanism of action

Answer 1

• prodrug
• breakdown to the active 5-aminosalisilic acid (5-ASA) [mesalazine]
• site of action in the colon
• moa not clear but possibly inhibits prostaglandin and leukotriene biosynthesis

Question 2

sulfasalazine in the stomach

Answer 2

• Log P = 3
• OH, COOH, SO2NH not ionised
• pyridine is fully ionised at pH in stomach
• Log D = 0 no absorption across stomach membrane
• drug travels to small intestine

Question 3

sulfasalazine in ileum

Answer 3

• SO2NH dissociated
• OH, pyridine not ionised
• COOH is fully ionised and so molecule not absorbed
• molecule is large and so it passes through to the colon where it is cleaved to 5-ASA

Question 4

sulfasalazine in colon

Answer 4

• OH, SO2NH, pyridine not fully ionised
• COOH is fully ionised at pH = 7.8 and is not absorbed passively
• molecule is cleaved by gut flora to 5-ASA

Question 5

mesalazine (5-ASA) in colon

Answer 5

• OH and NH2 not ionised
• COOH is fully ionised at pH = 7.8 so no passive diffusion
• BUT it may absorb through aqueous gaps in between epithelial cells as it is a small molecule

Question 6

steroid backbone structure

Answer 6

• three 6 membered rings
• one 5 membered ring hydroxyl groups known as sterols

Question 7

steroid mechanism of action

Answer 7

• act on glucocorticoid receptor
• regulates genes controlling inflammation/development/metabolism