Prostaglandins, Leukotrienes, and Essential Fatty Acids

Question 1

Prostaglandins and leukotrienes

Answer 1

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

Question 2

2 different routes for eicosanoid biosynthesis

Answer 2

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

Question 3

Initial precursor of all other prostaglandins

Answer 3

PGH2

Question 4

NSAIDs

Answer 4

Inhibit PGH-synthase

Reversible competitive inhibition of arachidonic acid oxygenation by cyclooxygenase

Question 5

Acetominophen

Answer 5

Weak inhibitor of arachidonic acid oxygenation

Used to stop cyclooxygenase in brain where peroxide levels are lower than in peripheral joints

Question 6

COX-2 inhibitors

Answer 6

Show selectivity for the inducible form of cyclooxygenase

Reduce side effects of gastric irritation and ulceration

Question 7

Design of eicosanoid drugs

Answer 7

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

Question 8

Eicosanoid receptor classes

Answer 8

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

Question 9

Ophthalmic use of eicosanoids

Answer 9

Treat glaucoma or ocular hypertension

Lower eye pressure

Question 10

Focuses of clinical development of prostaglandin-related drugs

Answer 10

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