Prostaglandins, Leukotrienes, and Essential Fatty Acids Flashcards Preview

Med Chem > Prostaglandins, Leukotrienes, and Essential Fatty Acids > Flashcards

Flashcards in Prostaglandins, Leukotrienes, and Essential Fatty Acids Deck (10):
1

Prostaglandins and leukotrienes

Termed eicosanoids
Derived from arachidonic acid
Released by phospholipase (PLA2) in response to traumatic event

2

2 different routes for eicosanoid biosynthesis

Cyclooxygenase pathway (synthesis of prostaglandins and thromboxane)
Lipoxygenase pathway (synthesis of leukotrienes)

3

Initial precursor of all other prostaglandins

PGH2

4

NSAIDs

Inhibit PGH-synthase
Reversible competitive inhibition of arachidonic acid oxygenation by cyclooxygenase

5

Acetominophen

Weak inhibitor of arachidonic acid oxygenation
Used to stop cyclooxygenase in brain where peroxide levels are lower than in peripheral joints

6

COX-2 inhibitors

Show selectivity for the inducible form of cyclooxygenase
Reduce side effects of gastric irritation and ulceration

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Design of eicosanoid drugs

Hard to do: chemical complexity and instability, rapid degradation, and likelihood to affect many tissues
Structural analogs resist degradation and keep biological activity, but side effects are much worse due to longer half life
Can be used to induce miscarriage

8

Eicosanoid receptor classes

Relaxant (DP, EP2, EP4, IP): smooth muscle relaxation due to increased levels of cAMP
Contractile (EP1, FP, TP): smooth muscle contraction due to Ca ion mobilization
Inhibitory (EP3): prevents contraction by lowering cAMP levels

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Ophthalmic use of eicosanoids

Treat glaucoma or ocular hypertension
Lower eye pressure

10

Focuses of clinical development of prostaglandin-related drugs

Lots of work still to be done: drugs are metabolized quickly and are very potent
Work needs to be done on developing specificity of these drugs and controlling their clearance