PENGERTIAN EIKOSANOID

“Eicosa” adalah kata Yunani untuk angka 20

Eikosanoid disintesis dari asam lemak dari asam lemak
polyunsaturated yang mempunyai 20 atom karbon

Salah satu pengatur fungsi sel yang paling kuat, dan dihasilkan
oleh hampir setiap sel tubuh
 Fungsi Fisiologis dalam Tubuh
Berfungsi sebagai hormon lokal

Respons peradangan yang terjadi setelah infeksi atau cedera

Mengatur kontraksi otot polos (usus & rahim)

Meningkatkan ekskresi air & Na oleh ginjal

Mengatur tekanan darah

Sebagai modulator : vasokonstriktor & vasodilator

Sebagai modulator bronkokonstriksi & bronkodilatasi

 Eikosanoid meliputi

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

• Thromboxane A2 menyebabkan agregasi platelet

• Leukotrien merupakan proinflammatory;

menstimulasi invasi leukosit dan meningkatkan
aktivitasnya. Pada reaksi anafilaktik, leukotrien
menyebabkan vasodilatasi, meningkatkan
permeabilitas vaskular dan menyebabkan
bronkokontriksi dan vasokonstriksi.
 Farmakokinetika
• The eicosanoids all have short plasma half-
lives (typically 0.5—5 min).
• Most catabolism occurs in the lung.
• Metabolites are excreted in the urine.
• Thromboxane A2 (TXA2) is rapidly hydrated to
the less active TXB2.
• PGI2 is hydrolyzed to 6-keto-PGF1α.
Jaringan pensintesis eikosanoid
Various eicosanoids are synthesized throughout the
body
Synthesis can be very tissue specific:
• PGI2 is synthesized in endothelial and vascular
smooth muscle cells.
• Thromboxane synthesis occurs primarily in
platelets.
• HPETEs, HETEs, and the leukotrienes are
synthesized predominantly in mast cells, white
blood cells, airway epithelium, and platelets.
 Action
Vascular smooth muscle

• PGE2 and PGI2 are potent vasodilators in

most vascular beds.

• Thromboxane is a potent vasoconstrictor.

 Action
Inflammation
• PGE2 and PGI2 cause an increase in blood flow
and promote, but do not cause, edema.

• HETEs (5-HETE, 12-HETE, 15-HETE) and

leukotrienes cause chemotaxis of neutrophils
and eosinophils.
 Action
Bronchial smooth muscle
• PGFs cause smooth muscle contraction

• PGEs cause smooth muscle relaxation

• Leukotrienes and thromboxane are potent

bronchoconstrictors and are the most likely
candidates for mediating allergic bronchospasm.
 Action
Uterine smooth muscle
PGE2 and PGF2a
 cause contraction of uterine smooth muscle in
pregnant women.

The nonpregnant uterus has a more variable

response to prostaglandins
 PGF2a causes contraction
 PGE2 causes relaxation.
 Action
Gastrointestinal tract
• PGE2 and PGF2a
» increase the rate of longitudinal contraction in the gut
and decrease transit time.
• The leukotrienes
» are potent stimulators of gastrointestinal smooth
muscle.
• PGE2 and PGI2
» inhibit acid and pepsinogen secretion in the stomach.
• Prostaglandins
» increase mucus, water, and electrolyte secretion in the
stomach and the intestine.
 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 - Meloxicam
 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.
Induction of labor is produced by:
 infusion of PGF2a (carboprost tromethamine)
[Hemabate] or
 PGE2 (dinoprostone) [Prostin E].
 Penggolongan terapi

Maintenance of ductus arteriosus

– is produced by PGE1 [Prostin VR] infusion

– PGE1 will maintain patency of the ductus

arteriosus, which may be desirable before surgery.
 Penggolongan terapi

Treatment of peptic ulcer.

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

• local pain and irritation

• bronchospasm
• gastrointestinal disturbances: nausea,
vomiting, cramping, and diarrhea.
TERIMAKASIH