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most abundant precursor to eicosanoids
arachidonic acid
found in membrane phospholipids
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what does 5,8,11,14- eicosatetraenoic acid lead to
- 2 series prostaglandins
- 4 series leukotrienes
source: diet
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what does 5,8,11,14,17 eicosapentaenoic acid lead to
5 series leukotrienes
source: fish oils
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what does 8,11,14 eicosatrienoic acid lead to
1 series prostaglandins
source:
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meaning of the "letter" in naming prostaglandins and thromboxanes
cyclopentane or oxetane ring substituents
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meaning of the "number" in maning prostaglandins and thromboxanes
the number of double bonds on side chains
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meaning of "letters" in naming leukotrienes
refer to adducts to arachidonic acid
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meaning of "numbers" in naming leukotrienes
refer to number of double bonds in fatty acid
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most common prostaglandins
1 and 2 series
2 series more prevalent in most tissues
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in what tissues are prostaglandins stored
they are not stored in tissues; their precursors are stored in nearly every tissue in the body
-
the one tissue that does not store prostaglandins
red blood cells
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tissues have different profiles of arachidonic acid metabolites
true
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first step in synthesis of prostaglandins
activation of phospholipase A2
this cleaves arachidonic acid from esterified form in the cell membrane
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what converts prostaglandin H2 to thromboxane A2
thromboxane synthase
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what converts prostaglandin H2 to prostaglandin I2
prostacyclin synthase
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organ that rapidly degrades PGE and PGF
lung
PGE and PGF lose over 90% of activity after one pass through lung
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role of PGE2 and PGI2 in CV system
vasodilators
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role of TXA2 in CV system
vasoconstrictor
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role of PGI2 on platelets
antiaggretory
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role of TXA2 on platelets
proaggretory
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role of PGE and PGF 2alpha on uterine smooth muscle
increase tone during pregnancy
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role of PGE on GI secretions
inhibits gastric acid secretion
stimulates mucus secretion (cytoprotective role)
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role of PGE2 and PGI2 in kidney
- increase renal blood flow
- - diuresis, natriuresis, kaliuresis
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role of TXA2 in kidney
- decreases renal blood flow
- decreases GFR (glomerular filtration rate)
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role of PGE2 and PGI2 on afferent neurons
hyperalgesia (potentiate pain response)
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role of prostaglandins on the immune system
modulate leukocyte activity (production of interleukins, adhesion molecules, TNF)
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role of prostaglandins in thrombosis
a balance between PGI 2 and TXA2
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prostaglandins participating in parturition
PGF2alpha, PGE2
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prostaglandins that regulate bronchial smooth muscle
PGF2alpha, TXA2
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prostaglandins that regulate renal blood flow and salt excretion
PGI2 and PGE2
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prostaglandins important for inflammation and immunity
PGE2 and PGE1
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Alprostadil (PGE1)
maintain patency of ductus arteriosus (countered by indomethacin to close ductus arteriosus)
tx erectile dysfunction
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misoprostol (PGE1) indications
prevent NSAID induced ulcers
prevent renal transplant rejection
used with RU-486 or methotrexate to terminate pregnancy
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misoprostol mechanism of action
decrease gastric acid production
immunosuppressive
contracts pregnant uterus
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misoprostol side effects
uterine contraction (contraindicated in pregnancy)
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dinoprostone
leads to labor (ripening and dilation of the cervix)
-
lubiprostone
used for chronic constipation
activates chloride channels (increases Cl into intestine lumen, Na and water follows)
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what synthesizes leukotrienes
leukocytes
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effects of LTC4, LTD4, LTE4 (all leukotrienes)
potent vasoconstrictors
proinflammatory
- bronchoconstrictors (involved with asthma)
- -involved with Adult Respiratory Distress Syndrome (ARDS)
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zafirlukast and montelukast effects
antagonize LTC4, LTD4, LTE4
cys-LT1 receptor antagonists
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zafirlukast and montelukast uses
- relax bronchiole smooth muscle in asthma pt
- -not for acute asthma attack, the effects take about a week
- decrease daytime asthma Sx
- decrease nighttime awakening from asthma
both completely metabolized by the liver CYP450 enzymes
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zafirlukast drug interactions
warfarin
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montelukast drug interactions
does not inhibit CYP 450 liver enzymes
-
zileuton pharmacology
5-lipoxygenase inhibitor
leads to relaxation of bronchial smooth muscles
-
zileuton uses
Tx mild to moderate asthma
rapidly absorbed
half life of 2.5 hrs
metabolized by liver P450 enzymes
-
zileuton drug interactions
increases serum concentrations of warfarin and theophylline
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