Prostaglandins & leukotrienes

1. Prostaglandins & Leukotrienes Dr.Sangeetha Purushothaman

2. Prostaglandins & Leukotrienes Local hormones - very active,many functions.. Autacoids from 20 C PUFA Prostaglandins Prostacyclin Thromboxanes Leukotrienes

3. Functions Inflammation Smooth muscle tone Blood coagulation Reproduction GI secretion

4. . . PHOSPHOLIPIDS ARACHIDONIC ACID PG G 2 PGH 2 PG I 2 LT A 4 THROMBOXANE A 2 PGE 2 PG D 2 PG F 2 LT C 4 LT D 4 LT B 4 PHOSPHOLIPASE A 2 5 LIPOOXYGENASE CYCLOOXYGENASE ISOMERASE PROSTACYCLINE SYNTHASE THROMBOXANE SYNTHASE SYNTHESIS

5. . PHOSPHOLIPIDS ARACHIDONIC ACID PG G2 PGH2 PG I2 LT A4 THROMBOXANE A2 PGE2 ,PG D2 ,PG F2 LT C4 LT D4 LT B4 PHOSPHOLIPASE A2 5 LIPOOXYGENASE CYCLOOXYGENASE STEROIDS ZILEUTON NSAIDS

6. BIOSYNTHESIS OF PROSTAGLANDINS AND LEUKOTRIENES Membrane phospholipid Arachidonic acid PG G2 LTA4 5HPETE PGH2 LTB4 LTC4 LTD4 Isomerases Thromboxane synthase Prostacyclin synthase Phospholipase A C yclooxygenase L ipoxygenase PGE2 PGD2 PGF2 TXA2 TXB2 PGI2 6 keto PGF2 α

7. BIOSYNTHESIS OF PROSTAGLANDINS Enzyme is Cyclo oxygenase (COX) COX 1-constitutive. COX 2-inducible NSAIDS- Nonselective COX inhibitors. COXIBS - Selective COX inhibitors Aspirin- Irreversible inhibition of COX Other NSAIDS- Reversible inhibition

8. Actions Inflammation Most important mediators.. S ynthesised as per need. NSAIDS

9. Actions –Smooth muscles Blood vessels Pg E 2 , Prostacycline - vasodilatation Thromboxane A 2 – constriction

10. Actions :Smooth muscle Bronchus

11. Uterus Both uterus &cervix

12. Actions GIT Natural ulcer protectants .. NSAIDS..

13. GIT

14. RENAL PgE 2 ,Prostacyclin - protective ..

15. Coagulation

16. PG I₂ ENDOTHELIUM PLATELET

17. . Penile erection CNS-Neurotransmitter EYE- ↓IOT Pulmonary vessels-vasodilatation

18. Preparations & Uses

19. Preparations Prostaglndin Preparation PgE ₁ Misoprostol , Alprostadil,Latanoprost PgE ₂ Rioprostil , Enprostil Dinoprostone PgF ₂ α Prostin 15Methyl PgF ₂ α Carboprost / Prostodin Pg I ₂ Epoprostenol

20. Uses 1.Obstetrics Therapeutic abortion Cervical ripening Severe Post partum hge PgE 1 /MISOPROSTOL PgE ₁ /PgE 2 15METHYL PgF 2 im /PgE 1 Rectal

21. 2.Peptic ulcer PgE 1 / Misoprostol PgE 2 / Enprostil,Rioprostil,Arbaprostil 3.Glaucoma : PgE 1 / Latanoprost 4.Erectile dysfunction 5. PDA 6. Primary pulmonary hypertention : PgI ₂ PgE 1 / Alprostadil

22. Summary of uses Use Preparation Abortion PgE1 Cervical ripening PgE1 / E2 Peptic ulcer PgE1 Glaucoma PgE1-Latanoprost PPH PgI2 PDA PgE1

23. ADR Vomiting,Diarrhoea,Abdominal cramps Uterine cramps Bronchospasm

24. LEUKOTRIENES

25. PHOSPHOLIPIDS CYCLOOXYGENASE PROSTAGLANDINS ARACHIDONIC ACID LEUKOTRIENES LIPOOXYGENASE LEUKOTRIENE RECEPTOR MAST CELL Zileuton Chromoglycate Nedochromil MonteleukastZafirleukast