Salah satu pengatur fungsi sel yang paling kuat, dan dihasilkan
oleh hampir setiap sel tubuh
Fungsi Fisiologis dalam Tubuh
Berfungsi sebagai hormon lokal
1. Prostaglandins
2. Thromboxanes
3. Leukotrienes
4. Hydroperoxyeicosatetraenoic
acids (HPETEs)
5. Hydroxyeicosatetraenoic acids
(HETEs).
•
Biosintesis
Asam Arachidonat, merupakan prekursor yang
paling umum dalam biosintesis eikosanoid.
Biosintesis
Eicosanoids are synthesized by two pathways:
1. The prostaglandin H synthase
(COX, cyclooxygenase) pathway produces:
A. thromboxane (TXA2)
B. the primary prostaglandins
- prostaglandin E, or PGE
- prostaglandin F, or PGF
- prostaglandin D, or PGD
C. prostacyclin (PGI2)
Biosintesis
2. The lipoxygenase pathway produces:
- HPETEs
- HETEs
- Leukotrienes
•
Prostaglandin, prostasiklin & TXA2
• Prostaglandin berperan dalam proses inflamasi dengan
meningkatkan sensitivitas nosiseptor, menurunkan ambang
nyeri dan memulai respon inflamasi dengan merilis mediator
inflamasi seperti interleukin-1, tumor-necrosis factor α dan
peningkatkan suhu tubuh.
•
• (PG)E2 menghambat sekresi asam lambung, meningkatkan
produksi mukosa lambung, menimbulkan bronkokonstriksi.
•
• PGF2α menstimulasi motilitas uterus (uterotonic).
•
• PGI2 (prostacyclin) menyebabkan vasodilatasi dan meningkatkan
ekskresi Na+ melalui ginjal, inhibisi agregasi platelet.
Prostaglandin, prostasiklin & TXA2
•
Action
Uterine smooth muscle
PGE2 and PGF2a
• menyebabkan kontraksi otot polos rahim pada
ibu hamil.
Rahim yang tidak hamil memiliki respons
yang lebih bervariasi terhadap
prostaglandin
PGF2a causes contraction
PGE2 causes relaxation.
Action
Gastrointestinal tract
• PGE2 and PGF2a
» meningkatkan laju kontraksi longitudinal
di usus dan mengurangi waktu transit.
• The leukotrienes
» stimulator kuat otot polos gastrointestinal.
• PGE2 and PGI2
» menghambat sekresi asam dan
pepsinogen di lambung.
• Prostaglandins
» Meningkatkan lendir, air, dan sekresi elektrolit di
lambung dan usus.
Action
Blood
• TXA2
» is a potent inducer of platelet aggregation.
• PGI2 and PGE2
» inhibit platelet aggregation.
• PGEs
» induce erythropoiesis by stimulating the
renal release of erythropoietin.
• 5-HPETE
» stimulates release of histamine
• PGI2 and PGD
» inhibit histamine release.
•
Penggolongan Farmakologi
• Phospholipase Inhibitors :
- Glucocorticoids ( Corticosteroids )
ex . Prednisone
•
Penggolongan Farmakologi
• Clooxygenase Inhibitors
1. Nonselectve Inhibitors : NSAID
• Salicylates (ex.aspirin),
• Propionic acid) (ex. Ibuprofen),
• Acetic acid (indomethacin),
• Oxicam (ex. Piroxicam)
• Fenamat (mefenamate),
• Acetaminophen
2. Cox-2 Selective Inhibitors
- Celecoxib - Valdecoxib
- Refecoxib
•
Penggolongan Farmakologi
• Prostanoid Receptor Mimetics
- Alprostadil (erectile disfunction) - Carboprost (aborstion)
- Misoprostol (ulcers) - Latanoprost (ocular hypertension)
• Thromboxane Antagonists
- Dazoxiben - Ridogrel
- Pirmagrel
• Leukotriene Inhibition
- Lipoxygenase inhibitor : Zileuton (asthma)
- Leukotriene Receptor Antagonists
ex. Montelukast (chronic asthma)
Zafirlukast
Penggolongan terapi
Therapeutic abortion:
A. Inducing abortion in the second trimester:
Infusion of carboprost tromethamine or
Administration of vaginal suppositories
containing dinoprostone
B. inducing first-trimester abortion:
• these prostaglandins are combined with
mifepristone (RU486)
Penggolongan terapi
Induction of labor at term.
infusion of PGF2a (carboprost
tromethamine) [Hemabate] or
PGE2 (dinoprostone) [Prostin E].
Penggolongan terapi
Maintenance of ductus arteriosus
–
• is produced by PGE1 [Prostin VR] infusion
Misoprostol [Cytotec]
• a methylated derivative of PGE1
• is approved for use in patients taking
high doses of nonsteroidal
antiinflammatory drugs (NSAIDs) to
reduce gastric ulceration.
•
Penggolongan terapi
Erectile dysfunction
Alprostadil (PGE1) can be injected directly into the
corpus cavernosum or administered as a
transurethral suppository to cause vasodilation
and enhance tumescence.
•
Adverse effects of eicosanoids