2. • PG is generic name for group of closely
related cyclic, oxygenated, 20C containing
unsaturated fatty acids.(PG,TAX2,LT,PAF)
• Derived from prostanoic acid 20c fatty acid
• Discovered in semen in 1930by Ulf
• “prostaglandin” name form prostate gland
where they were first thought to originate.
3. • The main inflammatory mediator derived
from membrane phospholipids are
eicosanoids
Phospholipids
Phospholipase A2
Arachidonic acid (Eicosa tetraenoic acid)
Eicosanoids (PGs,TAX2,LT,PAF)
prostanoids
Eicosa=20carbon,tetra =4 double bond
6. COX1Constitutive
PGI2
PGE2
TXA2
Housekeeping
Endothelial integrity
Vascular patency
Gastric mucosal
integrity
Bronchodilation
Renal function
Platelet function
COX2
Inducible
Inflammatory
PGE2
PGF2a
Proteases
Inflammation
Fever
Pain
NSAIDs
COX-1: platelets, gastric, renal constitutively expressed
COX-2: vessel wall, renal, induced in inflammation and cancer.
COX-3: controversial, thought to be a splice variant.
7. LT synthesis
• Leucko-trines first found in leucocytes,
trines- conjugated “triene” system of
double bond.
• Leuckotrines are products of lipoxygenase
pathway
• Lipoxygenase enzyme present in cytosol.
8. Biosynthesis of LT(Lipoxygenase pathway)
Membrane phospholipids
Phospholipase A2
(or PLC)
Arachidonic acid
5-Lipoygenase associated with protein FLAP
5HPETE
LTA4
LTB4,
LTC4
LTD4
LTE4
5-Hydroperoxy eicosatetraenoic acid
FLAP:- 5-lipoxygenase activating protein
11. • PAF- Gq-IP3/DA-Ca+2
Pharmacological actions of PAF:-
• Vasodilatation
• Vascular permeability
• Chemotatic to eosinophils and neutrophils
• Activation and aggregation of platelets
• PAF produced by foetus at final term, involved in
progression of labour.
• Most potent ulcerogen.
• PAF synthesis inhibited by Glucocorticoids.
12. Prostanoid receptors:
• Five main classes
Endogenous Ligand Receptor type G protein II messenger
PGD2 DP GS cAMP
PGF2 FP Gq IP3,DAG
PGI2 IP GS cAMP
TAX2 TP Gq IP3,DAG
PGE2 EP1 Gq IP3,DAG
EP2 GS cAMP
EP3 GS,Gi OR cAMP
Gq IP3,DAG
EP4 GS cAMP
13. Pharmacological action of prostanoids:
• Eye: PGF2 and PGE2 IOP by
uveoscleral pathway ( Drainage)
Respiratory system:
PGE2,PGI2- broncho dilatation
PGF2,TAX2, LT, PGD2-broncho constriction
broncho dilatation : broncho constriction
LT are powerful constrictors.
15. GIT: PGE2 Mucous production
PGE2,PGI2 Mucosal blood flow
Acid secretion
PGE2 water and electrolytic secretion (Diarrhoea)
Kidney: produced by renal medulla
PGE2,PGI2- Natriuresis
Renal vasodilatation
Inhibit ADH action
Stimulate renin release
PGE2 Cl- reabsorption
TAX2- Vasoconstriction
ADH like action
16. Platelet:
PGE1,PGI2 inhibit platelet aggregation
TAX2 -Platelet aggregation
-Low dose of aspirin acts an platelet (Inhibit
TAX2 production, platelets lack of nucleus
so it can’t synthesis cox-1 but vascular
produce cox-I) platelets
TX
PGHS-1:
collagen, thrombin, ADP.
PGI
PGHS-2:
shear,
bradykinin,
acetylcholine
+
-
17. Uterus: PGE2,PGF2α
• In vivo – Contraction
• In vitroPGE2 – Pregnant- Contraction
Non pregnant – Relax
PGF2α- Contraction
PG in low dose-Soften cervix
Male reproductive system:
Enhance penile erection ( Smooth muscle
relaxation blood flow)
CNS: PGE1,PGE2- Pyrogenic
18. • Peripheral nerve ending: PGs are
inflammatory mediators, sensitize pain
receptors
• Endocrine: Facilitate release of GH,TSH,
ACTH, FSH, LH and prolactin
• Bone metabolism: Stimulate bone
resorption
19. Therapeutic uses of prostanoids and analogues:
• Obstetrics:-
• PGE2, PGF2α used in terminate pregnancy
• First trimester:- Misoprostal PGE1, orally with
mefepristone/ Methotrexate to induce abortion in
first few weeks of pregnancy
• Second trimester:- Dinoprost(PGF2α) ,
• Carboprost intra amniotic inj- abortion least use
due to side effects.
• Dinoprostone(PGE2):- PGE2 –Vaginally for
inducing abortion, ripening of cervix for induction
of labour at full term. side effect- prolong
bleeding.
20. Facilitation of Labour, Cervical priming and
postpartum haemorrhage:
• For induction of labour oxytocin is DOC.
• PG is used for oxytocin CI i.e, renal failure,
pre-eclampsia, eclampsia. Advantage is
PG is does not cause Na, water retention.
• Demeprost / Denoproste used viginally
• Carboprost:- To control post- partum
haemorrhage.
22. To prevent platelet aggregation:-
PGI2- inhibit platelet aggregation epoprostenol-
renal dialysis.
To Treat Pulmonary Hypertension:-
• PGI2 lower peripheral pulmonary and coronary
resistance. IV infusion Epoprostenol, Treprostinil
Peripheral vascular disease: Beraprost- oral PGI2
–thrice a day
Treating glaucoma:LatanoprostPGF2α -
uveoscleral pathway (Drainage), Bimatoprost,
travaprost, Unoprostone
23. For Patency of Ductus Arteriosus:- PGE2,PGI2
having vasodilators, inhibit platelet aggregation
IV infusion – congenital heart disease,
pulmonary artery stenosis. Alprostadil(PGE1),
Epoprostenol(PGI2).
Male impotence:-Enhance penile erection
Bronchial asthma:- Bronchodilatation, but cough
side effect.
24. Side effects of Prostanoids:-
• PGs exhibit dose related adverse effects
bronchoconstriction, Hypotension,
Vomiting, diarrhoea, fever, dizziness, and
flushing.
• Carboprost:- Intra amniotic injection to
induce second trimester abortions can
cause anaphylactic shock and CVS
collapse.
25. • Alprostadil – maintaining the patency of
ductus arteriosus for long time leads
ductus fragility and rupture.
• Misoprostol, Enprostil – GIT discomfort
and diarrhoea.
• PGE (EP4) osteoclast and osteoblast
activity, induce hypercalciuria.
26. Drug Preparation Use
Dinoprostone Vaginal tab/gel Induction labour
Mid term abortion
Dinoprost Intra amniotic inj Mid term abortion
Carboprost IM, Intra amniotic inj Mid term abortion
Control of PPH
Gemeprost Vaginal pessary Cervical priming in early
pregnancy
Alprostadil IV infusion, IV inj
Intra cavernosal inj
Maintenance of a patent ductus
arteriosus in neonates
Erectile dysfunction
Misoprostol
Enoprostil
Oral Abortion & Peptic ulcer
Peptic ulcer
Epoprostenol IV infusion Pulmonary hypertension
Latanoprostol Topical Glaucoma
iloprost IM Dec. infact size, when given IM
after MI
