Leukotriene Antagonists

Immu Exam 2 Dr. Chichester Slideshow 2

what does 5-lipoxygenase do

initiate formation of inflammatory leukotrienes by oxidizing arachidonic acid

what do 12 and 15-lipoxygenase do

initiate formation of lipoxins

are lipoxins inflammatory or anti-inflammatory

anti-inflammatory

what is the effect of LTB4

chemoattraction of neutrophils and macrophages

what are the effects of LTC4, LTD4. and LTE4

bronchoconstriction, vasodilation, increase in local vascular permeability

where does LTB4 act

BLT1R receptors

where do LTC4, LTD4, and LTE4 act

CysLT1 and CysLT2

what is the first step in leukotriene synthesis

release of arachidonic acid onto the nuclear envelope

what is the second step in leukotriene synthesis

5-lipoxygenase oxidizes arachidonic acid to form LTC4S

what is the third step in leukotriene synthesis

glutithione conjugates LTC4S to make LTA4

what is the fourth step in leukotriene synthesis

LTA4 cleaves and becomes LTD4 and LTE4

how is LTB4 formed

hydrolase enzyme that hydrolyzes LTA4

why are leukotrienes produced

as a response to stress

what is the end result of the overproduction of leukotrienes

DNA damage

how do leukotrienes produce constriction

through M3 receptor; inositol triphosphate is released, causing Ca2+ to be released, causing smooth muscle contraction

zileuton

Zyflo

zileuton MOA

reduces formation of leukotrienes by blocking 5-lipoxygenase; blocks lipoxin synthesis

montelukast

Singulair

montelukast MOA

block leukotriene CysLTR1 receptor

zafirlukast

Accolate

zafirlukast MOA

blocks leukotriene CysLTR1 receptor

leukotriene modifiers are useful in treating what

aspirin-sensitive asthma

zyleuton has what kind of effect in RA, IBS, psoriasis

limited effect

how can NSAIDs trigger asthma

inhibit COX which results in increased levels of arachidonic acid, which results in increased levels of leukotrienes

what makes lipoxins

inflammatory cells, endothelial cells, epithelial cells

how are lipoxins made

LTA4 oxidation by 12 or 15-lipoxygenase

what targets do we want to inhibit in leukotriene synthesis

LTB4,  LTC4