Eicosanoids Flashcards
Hormone-like compounds that are derived from 20-carbon atom eicosanoic acids such as arachidonic acid and timnodonic acid
Eicosanoids
Eicosanoid examples
Prostaglandin Thromboxane Prostacyclin Leukotriene Lipoxin
Eicosanoid Biomedical Importance
Modulating the vascular tone, platelet Platelet aggregation Gastric secretion Salt and water balance Mediating pain and inflammatory responses
Drugs that act to reduce inflammation and provide pain relief by blocking the production of prostaglandins through inhibition of cyclooxygenase
Nonsteroidal anti-inflammatory drugs
Blocks prostaglandin release by inhibiting phospholipase A2 activity so as to interfere with mobilization of arachidonic acid
Steroidal anti-inflammatory drugs
NSAIDs block prostaglandin production via
Cyclooxygenase inhibition
Steroids block prostaglandin release by inhibiting
phospholipase A2 activity to interfere with mobilization of arachidonic acid
Acts on the SMOOTH MUSCLE
Used to induce parturition and for the termination of unwanted pregnancy
PGE2
PGF2
Membrane phospholipid is converted into arachidonate via
Phospholipase A2
Phospholipase A2 that converts membrane phospholipids to arachidonate is stimulated by
various stimuli angiotensin II bradykinin epinephrine thrombin
Arachidonate is further converted into either
Lipoxygenase
Cyclooxygenase
Lipoxygenase
Leukotrienes
Lipoxins
Cyclooxygenase
Prostaglandins
Thromboxanes
Cyclooxygenase hww a remarkable property of switching off prostaglandin formation by its
self-catalyzed destruction
Self-catalyzed destruction of cox is due to the action of
15-hydroxyprostaglandin dehydrogenase
Constitutively expressed
Inhibited by NSAIDs
Blocking this cyclooxygenase isoform results in
gastritis
GI bleeding
COX-1
Made only in response to inflammatory mediators such as cytokines
Inhibited by NSAID
COX-2
Block COX-2 and are called COX-2 specific inhibitors
Do not cause gastric irritation and bleeding
COX-2
Produced by endothelial cells of blood vessels
Causes vasodilation
Inhibits platelet aggregation
Increases formation of cAMP
Prostacyclin PGI2
Produced primarily by platelets Promotes platelet aggregation Decreases formation of cAMP Causes vasoconstriction Mobilizes intracellular calcium Stimulates concentration of smooth muscle
Thromboxane A2
Drug that inhibits TXA2
Aspirin
Produced by most tissues especially the kidney
Causes arteriolar vasodilation
Increases capillary permeability
Evokes chemokinesis of T cells
Enhances pain caused by histamine and bradykinin
Relaxes smooth muscle
Used to induce labor
PGE2
PGE1 analog used to induce labor
Misoprostol
Produced in leukocytes
platelets
mast cells
heart and lung vascular tissues
Leukotriene A4 LTA4
Contraction of snooth muscle Bronchoconstriction Vasoconstriction Increased vascular permeability Components of slow-reacting substance of anaphylaxis (SRS-A)
LTC4 -> LTD4 -> LTE4
Arachidonjc acid is converted into
15-lipoxygenase
15-lipoxygenase is converted into
15-HPETE
15-HPETE is converted into
5-lipoxygenase
5-lipoxygenase is converted into
Lipoxins
Family of unconjugated tetraenes also arising in leukocytes
Exhibit vasoactive and immunoregulatory function
Lipoxins (LXA4)
A 20 - carbon Omega 6 Fatty Acid with 4 double bonds
Arachidonic acid:
5-LOX -> 5 HPETE -> Leukotrienes
COX -> TXA, Prostacyclin (PGI2), Prostaglandin (PGE, PGF)
In prostate glands
Prostaglandin
On thrombocytes
Thromboxane
In leukocytes
Leucotrienes
PGH2 or Cycloendoperoxidases from COX
PGI
TXA2
PGE
PGF2a
Acts on endothelium
Antiplatelet aggregation
Vasodilation
PGI
Smooth muscle contraction
Vasodilation
PGE2
Released by platelet
Platelet aggregation
Vasoconstriction
TxA2
Smooth muscle contraction
Vasoconstriction
PGF2a
Inflammation
Bronchoconstriction
Vasoconstriction
Capillary permability
Leukotrienes
Material originally identified by bioassay from tissues of animals in anaphylactic shock; now recognized as a mixture of leukotrienes, especially LTC4 and LTD4
Slow-reacting Substance of Anaphylaxis SRS-A
Used in the treatment of impotence by injection into cavernosa of a urethral suppository
PGE1
Alprostadil
Cause contraction of the uterus
Approved for use to soften the cervix at term before induction of labor with oxytocin
Dinoprostone
PGE2
Cause contraction of uterus
Used as abortifacients in the second trimester of pregnancy
Produce more GI effects than oxytocin
PGE2
PGF2a
The PGE1 analog used with progesterone antagonist Mifepristone (RU 486) as an extremely effective and safe abortifacient combination
Approved for the prevention of peptic ulcers in patients who must take high doses of NSAIDs for arthritis and who have a history of ulcer associated with this use
May cause diarrhea
Misoprostol
Given as an infusion to maintain patency of the ductus arteriosus in infants with transposition of the great vessels until surgical correction can be undertaken
PGE1
Approved for use as epoprostenol in severe pulmonary hypertension and to prevent platelet aggregation in dialysis machines
PGI2
PGF2a derivative used extensively for the topical treatment of glaucoma
Reduce intraocular pressure, apparently by increasing outflow of aqueous humor
Latanoprost
Bimatoprost
Travoprost
Unoprostone
Selective inhibitor of lipoxygenase inhibiting leukotrienes
Zileuton
Inhibitor at CysLT1 receptor of LTD4 and LTE4 receptor
Montelukast
Zafirlukast
When COX is blocked, this is produced in increased amounts by diversion of prostaglandin precursors into the lipoxygenase pathway
Leukotrienes
Chemotactic factor in inflammation
Local release
LTB4
Activates TP alpha beta receptors
Causes platelet aggregation
Vasoconstriction
TXA2
Parenteral or inhalation form of PGI2 analog for pulmonary hypertension
Treprostinil
Reversibly inhibits COX-1 and COX-2
Reduces synthesis of prostaglandin
Ibuprofen
Indomethacin
Naproxen
Irreversibly inhibits COX-1 and COX-2
Reduces synthesis of prostaglandins
Aspirin
Reversibly inhibits phospholipase A2
Reduces synthesis of COX, LOX enzymes
Corticosteroids
Injectable COX
Parecoxib
Prodrug of Valdecoxib
FDA banned because it increases HTN
Etoricoxib
Arcoxia
Banned because of CV effects
Rofecoxib
