Escolar Documentos
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Cultura Documentos
Dr.C.V.NARASIMHA MURTHY
INTRODUCTION
These are a class of eicosanoids and were discovered
through their effect on smooth muscle.
Produced & released by nearly all mammalian cells;
(Except RBCs)
Perform a variety of functions
These are produced in minute amounts and are not
stored.
CLASSIFICATION
Cyclooxygenase Lipoxygenase
STRUCTURE
The structure of PG is based on hypothetical 20C parent saturated acid
called “Prostanoic Acid”
All naturally occuring PGs are 20C fatty acids containing a cyclopentane
ring.
All PGs have:
-OH group at 15th position
trans double bond at 13th position
CLASSIFICATION OF PGS
PG-E group: PGE-1, PGE-2 & PGE-3
Functional group: βhydroxyketone
PG-F group: PGF1α, PGF2α & PGF3α
Functional group: 1,3-diols
PG-A group: PGA-1, PGA-2 & 19-OH PGA-1
CELL
ARACHIDONIC ACID
CYCLIC-ENDO-
PEROXIDES
Peroxidase
PHYSIOLOGICAL EFFECT
CYTOTEC
Also known as misoprostol, manufactured by Searle (pfizer)
Cytotec was approved 12 years ago by the FDA for its intended
purpose: to prevent ulcers in people who take non-steroidal anti-
inflammatory drugs like aspirin or naproxen. misoprostol is a
synthetic PGE1 analogue
When administered, misoprostol
stimulates increased secretion of the protective mucus that lines
the gastrointestinal tract
increases mucosal blood flow, thereby increasing mucosal
integrity.
It is sometimes co-prescribed with non-steroidal anti-
inflammatory drugs (NSAIDs) to prevent the occurrence of
gastric ulceration, a common adverse effect of the NSAIDs.
Used for inducing labor at or near term : 0.5mg/ml
Used for terminating pregnancy: 5μg/ml
PHYSIOLOGICAL EFFECTS
PHYSIOLOGICAL EFFECT
Platelet Aggregation &
Thrombosis
PGI2: ( Inhibit Aggregation)
Released by endothelial cells
Mepacrine - Inhibits
phospholipase A
Gluco-corticoids Cortisol, Inhibit the
Betamethasone transcription of
PGHS-2
NSAIDS Aspirin, Inhibit COO
indomethacin,
ibuprofen
Cu++ & Inhibit PGE
dihydrolipoamide formation but
increses PGF
STIMULANTS
Trauma, hypoxia, angiotensin II, bradikinin, Vassopressin,
increase PG synthesis by activating Phospholipase A2
Catecholamines enhance PG synthesis by activating
COO
Addition of G-SH stimulates synthesis of PGE
NSAID: ASPIRIN
Acetyl salicylic acid (Aspirin) is an effective anti-platelet aggregator.
It irreversibly acetylates the platelets COO system and inhibits it thus hampering in
formation of Thromboxane A2
At time same time it opposes the formation of PGI2 in the endothelial cells, which is
a vasodilator.
CLINICAL USES:
Management of angina & MI
stomach.
In some experiments, the reaction was terminated by decreasing the
pH to 3 with HCl, and then extracting the sample.
The extracts were dried under reduced pressure. The residue was
chromatographed on TLC plates with markers of authentic PGE2 &
PGF2α. The area on the strip corresponding with the marker was
scraped in a test shaken with a medium. It was then assayed on rat
colons & stomach strips.
The zero time activity of PGE2 was 120-750ng and that of PGF2α was
60-150ng.
This activity didn’t increase when cell extract was incubated without
arachidonic acid.
On incubation with arachidonic acid, the activity of PGE2 increased by
100-500ng/ml and 220-520ng/ml for PGF2α.
Experiment: Test for Inhibition
To test the inhibition of prostaglandin synthesis, varying
amount of indomethacin, sodium acetylsalicylate, sodium
salicylate were added to the incubation flask. The inhibitor
of generation by a drug is expressed as the percentage
inhibition of the control generation.
Indomethacin, sodium acetylsalicylate, sodium salicylate
all inhibited the generation of PG like activity.
By calculating the ID50 it was inferred that indomethacin
was 23 times more potent than aspirin as an inhibitor of
synthesis of PGF2α and sodium salicylate was less potent
than aspirin for the same purpose.
Similar results were obtained for PGE2 activity on stomach
strips.
Two different lung homogenate enzyme samples were taken and
incubated with arachidonic acid.
The zero time activity for PGF2α was 40ng/ml and that of PGE2 was
5ng/ml.
After 30’ incubation activity increased to 160ng/ml for PGF2α and
50ng/ml for PGE2.
After incubation with indomethacin or aspirin there was no increase in
the activity of PGs over zero time.
The results show that the three anti-inflammatory acids inhibit the synthesis of
prostaglandins.
CONCLUSION
The generation of prostaglandins by a cellfree enzyme
preparation in vitro was measured by bioassay.
Aspirin-like drugs inhibited the formation of
prostaglandins. This enzyme inhibition was proposed as
the mechanism of therapeutic action and side effects of
aspirin-like drugs, implicating prostaglandins in
inflammation.