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What are the 3 lipoxygenase enzymes and their major sites of action?
5-lipoxygenase = white cells = leukotrienes (most important clinically)
12-lipoxygenase = platlets
15-lipoxygenase = macrophages & epithelial cells
What is the path of leukotriene formation via 5-lipoxygenase? what do they collectively form? What is the physiologic manifestation?
Arachodonic acid > 5-HPETE > LTA4 > LTB4
or LTA4 > LTC4 > LTD4 > LTE4 (via LTC4 synthase)
All these for slow-reacting substance (SRS) of anaphylaxis and cause bronchospams
What are the leukotriene receptors and where are they found?
- BTL: LTB4 in neutrophils, lung, spleen
- cysTL1: LTD4 & LTE4 in smooth muscle especially in lung
- cystTL2: LTC4 in endothelium & smooth muscle
ALL activate PLC (phospholipase C)
zafirlukast & monteleukast
- cysTL1 blockers
- once a day dosage
- use for persistent asthma
- inhibits both COX 1 and 2
- via acetylation
Indomethacin & sulindac
Ibuprofen & meclofenamate
Cox 1 &2 inhibitor
partially selective COX 2 inhibitor
Celecoxib, Valdecoxib, Rofecoxib (vioxx)
- selective COX 2 inhibitors
- latter 2 were found to have increased risk of MI & stroke
What is the pathway for prostaglandins?
what is the prostaglandin pathway for vasculature?
what is the prostaglandin pathway for asthma?
what is the prostaglandin pathway for uterus?
what is the prostaglandin pathway for gastric secretion?
what is the prostaglandin pathway for platlets?
- treat peripheral vascular disease
- keeps ductus arteriosus patent in infants
- PGI along with PGE2 keep ductus open in fetus
closes ductus (unknown how)
- great for asthma
- inhibits PLA-2
- therefore inhibits the production of arachodonic acid
Dinoprostone (PGE2) & carboprost
- induce labor and abortions
- works through PLC path
- provide contractions
- reduce production of thromboxane A2 by platlet
- this inhibits platlet aggregation