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Prostaglandins
• PG is generic name for group of closely
related cyclic, oxygenated, 20C containing
unsaturated fatty acids.(PG,TAX2,LT,P...
• The main inflammatory mediator derived
from membrane phospholipids are
eicosanoids
Phospholipids
Phospholipase A2
Arachi...
Biosynthesis of eicosanoids
Phospholipids
Phospholipase A2
Arachidonic acid (Eicosa tetraenoic acid)

LT

PG

EET

Esterif...
Biosynthesis of Prostanoids
Corticosteriods Membrane phospholipids
Phospholipase A2
(or PLC)
NSAIDS (aspirin)

Arachidonic...
PGI2

COX1
Constitutive

PGE2

TXA2
NSAIDs
Inducible
COX2
Inflammatory

Housekee
ping
Endothelia
l
integrity
Vascular
pate...
LT synthesis
• Leucko-trines first found in leucocytes,
trines- conjugated “triene” system of
double bond.
• Leuckotrines ...
Biosynthesis of LT(Lipoxygenase pathway)

Membrane phospholipids
Phospholipase A2
(or PLC)

Arachidonic acid
5-Lipoygenase...
• Leukotriene Modulators:
 5-Lipoxygenase Inhibitor : Zileuton
 LT – Receptor Antagonists : Zafirlukast,
Montelukast, Ir...
Platelet activating factor
Membrane phospholipids

Acyl
Phospholipase A2
PAF
(or PLC)
Acetyl
transfe
Lyso-PAF
rase
deac
Ac...
• PAF-

Gq-IP3/DA-Ca+2

Pharmacological actions of PAF:•
•
•
•
•

Vasodilatation
Vascular permeability
Chemotatic to eosin...
Prostanoid receptors:
• Five main classes
Endogenous Ligand Receptor type

G protein II messenger

PGD2

DP

GS cAMP

PGF2...
Pharmacological action of prostanoids:
• Eye: PGF2 and PGE2 IOP by
uveoscleral pathway ( Drainage)
Respiratory system:
PGE...
CVS:
PGE2 –

Vasodilatation
Weak inotropic
CO
Capillary permeability
Ductus arteriosus continually keep it
patent, maintai...
GIT: PGE2
Mucous production
PGE2,PGI2 Mucosal blood flow
Acid secretion
PGE2 water and electrolytic secretion (Diarrhoea)
...
Platelet:
PGE1,PGI2 inhibit platelet aggregation
TAX2 -Platelet aggregation
-Low dose of aspirin acts an platelet (Inhibit...
Uterus: PGE2,PGF2α
• In vivo – Contraction
• In vitroPGE2 – Pregnant- Contraction
Non pregnant – Relax
PGF2α- Contraction
...
• Peripheral nerve ending: PGs are
inflammatory mediators, sensitize pain
receptors
• Endocrine: Facilitate release of GH,...
Therapeutic uses of prostanoids and analogues:
• Obstetrics:• PGE2, PGF2α used in terminate pregnancy
• First trimester:- ...
Facilitation of Labour, Cervical priming and
postpartum haemorrhage:
• For induction of labour oxytocin is DOC.
• PG is us...
Healing of peptic ulcer:• PGE2,PGI2 Mucous production
Mucosal blood flow
Acid secretion (Anti
ulcerogenic, cAMP)
Misoprost...
To prevent platelet aggregation:PGI2- inhibit platelet aggregation epoprostenolrenal dialysis.

To Treat Pulmonary Hyperte...
For Patency of Ductus Arteriosus:- PGE2,PGI2
having vasodilators, inhibit platelet aggregation
IV infusion – congenital he...
Side effects of Prostanoids:• PGs exhibit dose related adverse effects
bronchoconstriction, Hypotension,
Vomiting, diarrho...
• Alprostadil – maintaining the patency of
ductus arteriosus for long time leads
ductus fragility and rupture.
• Misoprost...
Drug

Preparation

Use

Dinoprostone

Vaginal tab/gel

Induction labour
Mid term abortion

Dinoprost

Intra amniotic inj

...
Prostaglandins
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Prostaglandins

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Prostaglandins

  1. 1. Prostaglandins
  2. 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. 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
  4. 4. Biosynthesis of eicosanoids Phospholipids Phospholipase A2 Arachidonic acid (Eicosa tetraenoic acid) LT PG EET Esterified Arachidonic acid DHET EET=Epoxy eicosa trienoic acids DHET= Dihydroxy eicosa trienoic acid
  5. 5. Biosynthesis of Prostanoids Corticosteriods Membrane phospholipids Phospholipase A2 (or PLC) NSAIDS (aspirin) Arachidonic acid Cyclooxygenase-II Cyclooxygenase-I Induced by cytokines dur Widely present PGG2 PGH synthase PGH2 PGI2 PGE synthase synthase TAX synthase PGI2 (PC) PGE2,PGF2α,PGD Vascular TXA2 endothelium platelets In
  6. 6. PGI2 COX1 Constitutive PGE2 TXA2 NSAIDs Inducible COX2 Inflammatory Housekee ping Endothelia l integrity Vascular patency Bronchod Gastric ilation mucosal Renal Platelet integrity function function PGE2 PGF2 Inflamm ation ProteasesFever Pain 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. 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. 8. Biosynthesis of LT(Lipoxygenase pathway) Membrane phospholipids Phospholipase A2 (or PLC) Arachidonic acid 5-Lipoygenase 5HPETE LTA4 LTB4, 5-Hydroperoxy eicosatetraenoic acid FLAP:- 5-lipoxygenase activating protein LTC4 LTD4 LTE4 associated
  9. 9. • Leukotriene Modulators:  5-Lipoxygenase Inhibitor : Zileuton  LT – Receptor Antagonists : Zafirlukast, Montelukast, Iralukast, Pranlukast
  10. 10. Platelet activating factor Membrane phospholipids Acyl Phospholipase A2 PAF (or PLC) Acetyl transfe Lyso-PAF rase deac AcCo etyl atio PAF A n Arachidonic acid
  11. 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. 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. 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.
  14. 14. CVS: PGE2 – Vasodilatation Weak inotropic CO Capillary permeability Ductus arteriosus continually keep it patent, maintain placental blood flow PGI2- Vasodilator Peripheral, pulmonary and coronary resistance PGF2α , TAX2- Potent vasoconstrictor
  15. 15. GIT: PGE2 Mucous production PGE2,PGI2 Mucosal blood flow Acid secretion PGE2 water and electrolytic secretion (Diarrhoea) Kidney: produced by renal medulla PGE2,PGI2Natriuresis Renal vasodilatation Inhibit ADH action Stimulate renin release PGE2 Cl- reabsorption TAX2Vasoconstriction ADH like action
  16. 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 + PGHS-1: collagen, thrombin, ADP. TX PGI PGHS-2: shear, bradykinin, acetylcholine
  17. 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. 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. 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. 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.
  21. 21. Healing of peptic ulcer:• PGE2,PGI2 Mucous production Mucosal blood flow Acid secretion (Anti ulcerogenic, cAMP) Misoprostol-oral -200µg- QD. Enoprostil- NSAIDs induced ulcer/chronic smokers
  22. 22. To prevent platelet aggregation:PGI2- inhibit platelet aggregation epoprostenolrenal 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. 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. 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. 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. 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 Maintenance of a patent ductus arteriosus in neonates Erectile dysfunction Intra cavernosal inj 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

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