Eicosanoids Flashcards
Clinical analog of Prostacyclin (PGI2) (2)
Epoprostenol, Iloprost
Clincal analog of PGE2 (3)
Misoprostol
Alprostadil
Dinoprostone
Clinical analog of PGF2a
Latanoprost
Name leukotriene receptor antagonist
Montelukast, Zafirlukast,
Name a lioxygenase inhibitor
Zileuton
What is omacor/lovaza
Omega-3 Fatty Acids
2 classes o f eicosanoids
- Prostaglandins
2. Leukotrienes
Eicosanoids are derived from/rate limiting step/enzye
Arachidonic Acid by Phospholipase A2
Main sourse of arachidonic acid
Dietary linoleic acid
Which enzyme is responsible for the production of prostaglandins
Cyclo-oxygenases
Which enzyme is responsible for the production of leukotrienes
Lipoxygenases
Half life for eicosanoids
- Have short half lives (<5 min) and act locally (autocoids)
- metabolized in tissues and excreted in urine
- do not circulate in blood
Which receptor do prostaglandins activate
G protein recptors
Can raise cAMP leves = smooth muscle reaxation
Activate PLC and raise Ca = smooth muscle contraction
Which prostglandins cause resp. smooth muscle to relax
PGE2, PGI2 = relax respiratory sm
Which prostglandins cause resp. smooth muscle to contract
PGF2a
Which prostaglandins cause longituidnal muscles in the GI system to contract (diarrhea & vomiting)
PGE2, PGF2a
Which prostaglanin causes circular muscle to relax
PGE2
Which prostglandins cause vascular constriction in smooth muscle
-TXA2, PGF2a
Which prostglandins cause vascular dilitation in smooth muscle
PGI2, PGE2
Which prostaglandins cause uterine constriction
-PGE2, PGF2a, TXA2 = contract
Which prostaglandins cause uterine dilatation
PGI2
Which prostglandins are cytoprotective (more mucus) to G.I.
PGE2
In asthma are the PGs or leukotirens more importat
eukotrienes are major mediators of asthma
Which leukotrienes most important in asthma
LTC4, LTD4 pathologic for asthma
Bronchoconstriction, inc mucus secretion, increased vasc permeability
Which prostglandin is major mediator of pain and fever
PGE2
Which prostglanins mediate dysenorrhea
PGE2 and PGF2
Which prostgladins regluate intraocular eye pressure
PGF2
How to corticosteriods exert their effect
Corticosteriods reduce the activity of PLA2 and synthesis of COX2
How does asprin exert its effect
aspirin irreversibly inhibit COXs while all other NSAIDs are reversible inhibitors - prevents vasoconstriction & platelet aggregation
Whay are COX2 inhibitors associates with adverse cardiac effects
Inhibit PGI2 vasodilatory effects and get uninhibited COx1/TXA2 vasoconstrictio
Which cell type ainly produces leukocytes
Leukotrienes
Second messanger for leukotriene receptors
IP3 with a subsequent increase in [Ca2+]
What is SRS-A = slow-reacting substance of anaphylaxis.
LTC4 and LTD4
ALso active in asthma
Mechanism for asprine induced hypersensitivity asthma
Know that aspirin induced hypersensitivity asthma may be
exacerbated by diverting arachidonic acid to leukotrienes (LTC4 and LTD4)
5 lipoxygebase inhibitor
Zileuton
Leukotriene receptor antagonist
Zarfirlukast
Montelukast
Misoprostol (Cytotex)
- Use
- Side Effect
- Contraindications
- BBW
Primarily used for ulcer prevention during long-tem NSAID therapy (FDA approved): increases mucus & bicarbonate secretion
Adverse effects
Diarrhea and occasional abdominal discomfort
Contraindication
Pregnancy due to uterotonic activity
BBW
Abortion & birth defects
What is used to keep PDA open
PGE2
What is used to close PDA
Ibuprofen
Indomethacin
Iloprost (Ilomedin)
- Use
- Mechanism
FDA approved for pulmonary hypertension
A stable second generation analog of prostacyclin
Alprostadil
- Mechanism
- Side Effect
PGE1 analog.
Vasodilator
Pharmacokinetics:
Can be injected directly into the cavernosa, used as a topical cream, or placed in the urethra as a minisuppository, from which it diffuses into the cavernosal tissue
Side Effects:
penile pain (29-49% of users)
urethral bleeding (5%)
hypotension within 1 hour of use (3.3%)
Zileuton
- Drug class
- Mechanism
- Indications
Drug Class:Leukotriene pathway inhibitor
Mechanism of Action:
orally activeinhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid
Indications:
prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. (
Montelukast
- Drug class
- Mechanism
Drug Class:Leukotriene Inhibitor
Mechanism of Action:
anLTD4-receptor antagonist
Indications:
for the prophylaxis and chronictreatment of asthmain adults and pediatric patients 6 years of age and older.
It is NOT indicated for use in the reversal of bronchospasm in acute asthma attacks.
Pharmacokinetics:
effective orally,taken once a day(typically in the evening)
Dexamethason
- Class
- Mechanism of action
- Indication
Drug Class:Glucocorticoid, Anti-Inflammatory
Mechanism of Action:Binds to intracellular glucocorticoid receptors and modulates gene expression.Glucocorticoids dramatically reduce the manifestations of inflammation due to their profound effects on the concentration, distribution, and function of peripheral leukocytes and to their suppressive effects on the inflammatory cytokines and chemokines and on other lipid and glucolipid mediators of inflammation.
Indications:
used for its potent anti-inflammatory effects in disorders of many organ systems.
Examples of indications include:rheumatic disorders, arthritis, lupus erythrematosus, bronchial asthma & ulcerative colitis.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune responses to diverse stimuli..
