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What cells produce prostanoids?
All cells
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What cells produce leukotrienes?
Lymphocytes and Macrophages
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What are the three important Prostanoids?
- Prostaglandin (PG)
- Prostacyclin (PGI)
- Thromboxane (TX)
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What is the predominate Omega, 3 or 6, in the american diet?
omega-6 >90%
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What is the number for a-linoleic acid?
18:3, omega-3
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What is the number for linoleic acid?
18:2, omega-6
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Out of the prostanoid derivatives EPA, DGLA and AA, which is the most inflammatory and prominent?
AA
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Which is a stronger platelet inhibitor, PGI2 or PGI3?
PGI3
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Which is a stronger platelet stimulator, TX2 or TX3?
TX2
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What are the cleaved products of Gs and Gq?
- Gs= Adenylyl cyclase = cAMP
- Gq= PLC = IP3 and DAG
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What is the four step process of prostaglandin and thromboxane production? (use AA)
- 1) Ca activated PLA2, moves to membrane
- 2) Release AA
- 3) Production of PGH2 utilizing COX and peroxide (PGH Synthase rxn)
- 4) Production of cell-specific prostanoid
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What is the RLE in prostanoid production?
PLA2
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What is the process of forming leukotrienes?
- 1) AA in lymphocyte or macrophage
- 2) AA + 5-lipoxygenase
- 3) 5-HPETE formed
- 4) LT formed
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How does asprin induce asthma?
- Asthma blocks COX
- This shunts AA away from PG and TX production and into LT production
- increased LT = more allregic/inflammation response
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Which is more common, COX-1 or COX-2?
- COX-1: made in most cells
- ***COX-2 is created during inflammation and immunity
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Which is more easily inhibited, COX-1 or COX-2 and why?
COX-2 b/c of a larger area for inhibitor binding
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Where are the five common areas of COX-2 production?
- Lung
- Brain
- Kidney
- Endothelium
- Bone
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What are the three keys to an NSAID?
- 1) Anti-inflammation
- 2) Analgesic
- 3) Antipyretic
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Which does aspirin inhibit most, COX-1 or COX-2?
COX-2
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What is the bleeding pathology of Aspirin?
increased GI bleeding b/c of platelet inhibition (PGI3) and weak platelet stimulation (TX3)
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What is the positive and negative of celebrex?
Positive: Blocks only COX-2 so it does not cause GI bleeding
Negative: increased risk of heart attacks
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What is the effect of steroids (glucocorticoids) on PLA2?
Inhibition
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What is the affect of annexin-1 on PLA2?
Inhibition
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What prostanoids do Gs and Gq receive?
- Gs: PGI2 = adenylyl cyclase and cAMP
- Gq: TX2 = PLC = IP3 and DAG
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What prostaglandins do COX-1 and COX-2 help produce?
- COX-1 = TX2 (platelets)
- COX-2 = PGI2 (endothelium)
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How are prostanoids inactivated?
At specific site of action
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How are prostanoids catabolized?
- In lungs
- Due to presence of 15-hydroxyprostaglandin dehydrogenase
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