Flashcards in Regal- Prostaglandins, Thromboxane and NSAIDS Deck (64)
How are leukotrienes synthesized?
Phospholipase A2 cleaves membrane phospholipids into AA
5 LPO converts AA to 5HPETE then LTA4
What do LTC4 synthase or glutathione S transferase do to LTA4? What converts LTE4 to LTB4?
Where does LT synthesis occur?
Many cells and tissues
Predominately synthesized in leukocytes
What enzyme is associated w/ mast cells and basophils and what to they primarily make?
What enzyme is associated with endothelial cells and smooth muscle cells?
Glutathione S transferase
What are the 2 (4) types of leukotrienes?
LTC4, LTD4, LTE4
How is LTB4 degraded?
Oxidized to inactive compound by enzymes in PMNs and others
What are the biological effects of LTB4?
Chemotactic for neutrophils
enhanced leukocyte adhesion
Decreased pain threshold--> hyperalgesia
What receptors does LTB4 target?
Non mentioned specifically but they're distinct from peptide LTs
How is LTE4 degraded?
It is excreted in urine or acetylated and excreted in bile
LTC4, LTD4, LTE4 act on what receptor?
Interaction of peptido leukotriens w/ LTR1 leads to...
increased vascular permeability-> swelling
chemotactic for eosinophils and cytokine secretion
increased mucous production
DC maturation and migration
smooth muscle proliferation
Interaction of peptido leukotrienes w/ LTR2 leads to...
endothelial cell and macrophage activation
What two peptido leukotrienes are important in asthma?
What drugs are leukotriene modifiers?
What is the therapeutic use of leukotriene modifiers?
CHRONIC not acute
What is the MOA of zileuton?
prevents synthesis of LTB4 and peptido LT
How is zileuton eliminated?
What are the toxicities associated with zileuton?
hepatic toxicity (req monitoring)
What is a unique property of zileuton related to asthma?
It can decrease the need for beta agonists in asthma
What is the MOA of zafirlukast and montelukast?
LTR antagonists (cys LTR1)
What is a toxicity associated w/ zafirlukast?
inhibits cyp450--> drug interactions
What is a unique property of montelukast?
it can be administered once daily w/out regard to meals
What are prostanoids?
How are prostanoids synthesized?
Phospholipase A2 cleave membrane bound phospholipids into AA>
Cox acts on platelets to form products
What cells produce cos?
numerous cells in response to different stimuli
Where is COX1 found?
constitutively expressed in most cells and is thought to protect mucosa
Where is cox 2 found? What products is it more involved inmaking?
not in platelets
more involved in production of PG and TXA in inflammation
How does enzyme expression of PG synthases influence the type of PG produced?
Platelets--> thromboxane (vasoconstrictor)
Endothelium--> prostacylcin (vasodilator)
Mast cells--> PGD2 (bronchoconstrictor)