The eicosanoids, so called because of their derivation
from a 20-carbon unsaturated fatty acid, arachidonic
acid (eicosatetraenoic acid), are obtained from membrane
phospholipids and synthesized de novo at the
time of cellular stimulation. Arachidonic acid is cleaved
from membrane-bound phosphatidylcholine by the enzyme
phospholipase A2. Alternatively, arachidonic acid
may be derived by the sequential actions of phospholipase
C and diacylglyceryl lipase. Arachidonic acid can
then follow either of two enzymatic pathways that result
in the production of inflammatory mediators. The production of
inflammatory eicosanoids is an important target of many
anti-inflammatory drugs. In addition, the side effects of
these drugs frequently result from their inhibition of
eicosanoid production.
A number of eicosanoids are used as therapeutic
agents. In infants with congenital heart anomalies, a
patent ductus arteriosus can be temporarily maintained
by the PGE1 analogue alprostadil (Prostin VR
Pediatric) until surgical correction can be performed.
Clinical Use
A number of eicosanoids are used as therapeutic
agents. In infants with congenital heart anomalies, a
patent ductus arteriosus can be temporarily maintained
by the PGE1 analogue alprostadil (Prostin VR
Pediatric) until surgical correction can be performed. In
patients undergoing treatment with nonsteroidal antiinflammatory
drugs, the PGE1 analogue misoprostol
(Cytotec) is often used to decrease gastric acid secretion,
thereby inhibiting the ulceration caused by these
agents. Misoprostol is also used in several non-
FDA–approved applications, including the induction of
labor by enhancing cervical ripening, and the induction
of abortion in combination with mifepristone (RU-486).
These uses of misoprostol are associated with an increased
risk of uterine rupture or perforation.
Dinoprostone (Prostin E2), a synthetic PGE2, causes
uterine contraction and is used clinically to induce abortion
during the second trimester and to empty the uterus following fetal death, missed abortion, or benign
hydatidiform mole. Carboprost (Hemabate) is a PGF2
analogue that can be used to terminate pregnancy or to
control refractory postpartum bleeding by stimulating
uterine contraction. Primary pulmonary hypertension
can be treated by the synthetic PGI epoprostenol
(Flolan). Elevated intraocular pressure may be treated
with latanoprost (Xalatan), an analogue of PGF2.
Zafirlukast (Accolate) is an oral leukotriene receptor
antagonist for control of the inflammatory process of
asthma. Zileuton (Zyflo) inhibits the
first enzyme in the lipoxygenase pathway and is used for
the treatment of asthma.
