12-NSAIDS

Question 1

NSAID medications

Answer 1

• Aspirin
• Traditional NSAIDs
  -COX2 selective inhibitors
• Acetaminophen ish

Question 2

Example of COX2 selective inhibitor

Answer 2

Celecoxib

Question 3

NSAIDs history

Answer 3

• White willow (Salix alba, 1828): plant remedy for pain& fever, but had serious side effects.
  -Meadowsweet leaves (spirea ulmaria) 1839
• Active ingredient: salicin

Question 4

Aspirin synthesis

Answer 4

• took spirea ulmaria (active ingredient salicin), made a acetyl derivative —> acetylsalicylic acid
• fewer side effects, first synthetic drug
• 1899, Hoffman —> Aspirin synthesized (first “pharmaceutical”) (unknown mechanism)
• 1971: mechanism of action - blocks prostaglandin synthesis

Question 5

NSAIDs pharmacodynamics

Answer 5

Block proastaglandin synthesis by COX1/2 enzymes

Question 6

Prostaglandin synthesis

Answer 6

• arachidonic acid in phospholipids, released by phospholipase (—>free AA), COX1/2 convert it to prostaglandins
• PGE2 most common, but many
• made by almost all cells
• autocrine and paracrine functions (don’t go to circulation, act where synthesized)
• rapidly inactivated

Question 7

Cyclooxygenase

Answer 7

• forming ring, adding 2 oxygens
• dimer
• Arachidonic acid enters in active site

Question 8

Where do prostaglandins act?

Answer 8

• act on G-protein coupled prostanoid receptors subgroups PGD, E, F, I & T (diff functions/effects)
• multiple receptors, cart on multiple organ systems
• eicosanoids: a big family, diverse effects (?)