Prostaglandins:
Definition: These are
the unsaturated fatty acid derivatives containing 20 carbons that include
cyclic structure.-sometimes referred to as eicosanoids("eicosa"-20)
Importance in inflammation: All the
NSAIDs act by inhibiting the synthesis of prostaglandins.
Features:
1. They are produced by virtually all the tissues of the body and are
released during the time of inflammation. They get inactivated once they
exerted their actions,
at the site of the actions. Hence they won't circulate in the blood.
2. Thromboxanes, leukotrienes, hydroperoxy eicosatetraenoic acid,
hydroxyeicosatetraenoic acid are those that are derived from the same
precursors as prostaglandins and are interrelated in various pathways.
Production of the eicosanoids
from the arachidonic acids:
It involves 2 pathways
1.Cyclooxygenase pathway: Two types of cyclooxygenase are present:
COX-1, COX2(For Pathway refer Lippicott Page 527)
COx-1: It involves mostly in the
physiological functions(ie. Physiologic Production of Prostanoids)
COX-2 are seen in increased
concentration in the conditions of chronic diseased states of the Kidney, Brain
and bone. (elevated production of Prostanoids)
COX-2 Has a larger substrate
channel than COX-1
2.Lipooxygenase pathway: Several lipooxygenases act on the arachidonic
acid to produce 5;12;15-HPETE Which are unstable peroxidative derivatives that
will be readily converted to HydroxyEicosaTetraEnoic Acid
Antileukotriene Drugs: Zileuton,Zafirlukast and montelukast
Prostaglandins analogs:
1.Misoprostol-PGE1-Prevent the ulcer formation during prolonged
treatment of NSAID
2.Iloprost-PGI2-Potent pulmonary vasodilator
3.Latanoprost-PGF(a1)-Open angle Glaucoma and elevated intraocular
pressure.
4.Travoprost-is a prodrug that is actively metabolized to a free acid-
administered as ophthalmic solutions once a day and are as effective as timolol
for the reduction of the intraocular pressure.
5. Bimatoprost-Mimics the endogenously prostanoids thereby used
effectively in the reduction of the intraocular pressure;-Also it is used to
increase the eyelash prominence, length, darkness- so approved for the
treatment of eyelash hypotrichosis
6.Alprostadil-PGE1 Analogue- Normally produced in the 1.Seminal vesicle
2.Cavernous tissues 3.Placenta 4.Ductus Arteriosus.
Uses: 1.Used in the treatment of the erectile
dysfunction[When administered locally via urethra(suppository) or corpus
cavernous(Injection) It causes erection that is suitable for the intercourse.]
2. It is used
to maintain the ductus arteriosus patent open after the delivery in case of
the congenital heart disease until the surgical correction is possible.
Side effects:1.In
treatment of the erectile dysfunction-causes hypotension, dizziness, syncope;
Further, it causes penile and testicular pain, prolonged erection and
priapism(erection in absence of sexual stimulus)
2.Administration in neonates causes
apnoea,sepsis,fever,seizures
7.Lubiprost-PGE1 analogue-Used for the treatment of chronic idiopathic
constipation and bowel irritation syndrome with constipation.
-Acts by stimulating
the Chloride channels(ClC-2) in the intestinal epithelium thereby increases the
chloride concentration in the intestinal lumen.This high concentration of the
chloride in the intestinal lumen softens
the stool and increases the intestinal motility.
-Side Effects:1. Nausea is the most important side effect
reported, which can be prevented by taking the drug with the food.
2. Dose-dependent diarrhea is the secondary side effect which then succeeded by Headache and abdominal pain.
Post a Comment