Prostaglandins

By
Dr. Fazlullah Khan
 Background

• Traced in semen (1930)

• Contraction effect in isolated uterus.
• Somehow decreased blood pressure
• Hence its was hypothesized that prostate
gland is releasing some kind of substances
which showing such effects.
• The prostaglandins (PG) are a group
of physiologically active lipid compounds
called eicosanoids.

• Having diverse hormone-like effects in animals.

• Prostaglandins have been found in almost

every tissue in humans and other animals.
• They are derived enzymatically from the fatty
acid Arachidonic acid.
• Prostaglandins play its role in; (release).
• Pain perception.
• Trauma.
• Inflammation.
• So in case we want to lower the level of
Prostaglandin by inhibit the basic biosynthesis
of prostaglandin we prescribe NSAIDS.
• NSAIDS mechanism of action as above..
❑Prostaglandins (PG) and leukotriene are
eicosanoid derivatives.
▪ Eicosanoids are 20 carbon unsaturated fatty
acids derived from Arachidonic acid in the cell
membrane.
▪ PG + Leukotriene= Eicosanoids
Principle Eicosanoids as Autacoids

• Prostaglandins (PG).

• Prostacyclin (PGI2)

• Thromboxane (TX)

• Leukotrienes (LT)

They initiate different physiological functions.

 Biosynthesis
• Two major pathways
1. Cyclooxygenase (COX)-pathway
2. lipoxygenase (LOX)-pathway

COX Pathway= PG + Thromboxane

LOX Pathway= Leukotrienes
COX-Isozymes:

(Isoenzymes are those enzymes which perform a

similar function but varies in structural and
biochemical properties).
1. COX-I
2. COX-II
3. COX-III
• COXI= Always present in the cell
• House keeping function.
• Gastro protective functions.
• Enhance secretion of bicarbonate ions.
• Neutralize the acid.
• Basic medium provision.
• Inhibit the gastric ulcer and associated problems
• COXII= Induced by oxidative stress, Injury,
Ischemia, Neurodegenerative disorder

• Particularly in inflammation.

• Constitutive in brain and kidneys

• COXIII= Recently isolated from cerebral cortex

• Not involved in inflammation.

• Role in body temperature regulation.

• Paracetamol= Affects COX-III in fever.

 Pharmacological actions

1). CVS: i). Prostacyclin and PGE2= Vasodilator

ii). TxA2= Vasoconstriction
iii). PGE2 and PGE2α= weak cardiac
stimulant.
2). GIT= i) Most PG and TX2 stimulate smooth
muscle……..watery diarrhoea.
ii) PGE2= Decrease acid production and Increase
mucus production.
3). Airway= i). PGE2 and PGI2 relax bronchial
smooth muscles contraction.

ii). TxA2 and PGE2α= Contract smooth muscles

and has a role in asthma.
4). Platelet:
i). TxA2= Increase platelet aggregation
ii). PGI2= Decrease P. aggregation.
iii). PGE2= Increase platelet aggregation in low
conc. Similarly, Decrease Platelet aggregation in
high conc.
5). Reproductive system:
i). PGE2 and PGE2α=
ii). contract uterus
iii). Soften cervix
iv). PG= initiate and progression of labour
 PG antagonists

• NSAIDs are perhaps the best-known

prostaglandin antagonists; they suppress the
signaling function of prostaglandins, which are
important mediators of pain, fever, and
inflammation responses
NSAIDS=

by inhibiting the cyclooxygenase enzymes and

thereby reducing prostaglandin synthesis.
• NSAIDs have been shown to increase the risk
of myocardial infarction when taken on a
chronic basis for at least 18 months. One
emerging hypothesis that may explain these
cardiovascular effects is that coxibs create an
imbalance in circulating TxA2 (thromboxane
A2) and PGI2 (prostacyclin) levels. An increase
in the ratio of TxA2/PGI2 could lead to
increased platelet aggregation and
dysregulation of platelet homeostasis.