Prostaglandins

1. Prostaglandins By Dr. Mirza Shahed Baig

2. What are Autacoids? • The word Autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug). • Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. • This are produced locally, act locally and are metabolised locally. • Autacoids can have many different biological actions including modulation of the activity of smooth muscles, glands, nerves, platelets and other tissues.

4. What are Eicosanoids? • Eicosanoidsare produced from arachidonic acid, a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid) • The eicosanoids are considered “autacoids" • They act on cells close to their site of production • They are rapidly degraded • They have both intercellular signaling, & intracellular signal cascades

7. What are Prostanoids? • Prostanoids are a subclass of eicosanoids • The term "prostanoids" relates to the products of the cyclooxygenase pathway • This molecules containing prostanoic acid as the central structural element. For that reason, they are named prostanoids.  • Prostanoids consist of the following • Prostaglandins (mediators of inflammatory and anaphylacticreactions). • Prostacyclins (active in the resolution phase of inflammation.)  • Thromboxanes (mediators of vasoconstriction),

8. Biosynthesis of Eicosanoids

11. Prostanoids Receptors • Prostanoid receptors are AC/PLC G-protein coupled Rs • Five main classes; DP (PGD2), FP (PGF2α),IP (PGI2),TP (TXA2),& EP (PGE2) • Eicosanoid synthesis is activated by: • Pathological stimulus: tissue injury/disease • Transmitter release like BK, AngII, NE

13. Prostaglandins (PG) • The prostaglandins (PG) are a group of physiologically active lipid compounds having diverse hormone-like effects in animals.   • They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives. • Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymaticallyfromfatty acids. • Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.

19. Chemistry of Prostaglandins (PG) Prostanoic Acid Nucleus

20. Chemistry of Prostaglandins

21. 1 unsaturated bond Saturated I

22. 1 unsaturated bond Saturated Bridged bicyclic system Bridged bicyclic system I 2 fused rings

31. Corticosteroids

32. Corticosteroids Class of drugs

34. MOA of Corticosteroids

35. Cortisol Fludrocortisone Prednisolone Dexamethasone Betamethasone Methylprednisolone

36. Prostacyclins • Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipidmolecules. • It inhibits platelet activation and is also an effective vasodilator. • When used as a drug, it is also known as epoprostenol.  The terms are sometimes used interchangeably.

37. Biosynthesis of Prostacyclins

38. Biosynthesis of Prostacyclins

39. Clinical effects of Prostacyclins

40. Prostacyclins Analogs

41. Use of Prostacyclin drugs

45. What are Thromboxanes (TX) • Thromboxane is a member of the family of lipids known as eicosanoids. • The two major thromboxanes are thromboxane A2 and thromboxane B2. • The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. • Thromboxane is named for its role in clot formation (thrombosis).

46. Types of Thromboxanes

47. Thromboxane Synthatase and Thromboxane Receptors • TXA2 is the major product of the arachidonic acid (AA) metabolism in platelets that, in response to various stimuli, is produced via the consequent actions of cyclooxygenase (COX) and TX synthase (TXS). • Thromboxane (TX) A2 is involved in a diverse range of physiological and pathophysiological processes, including thrombosis, asthma, myocardial infarction (MI), inflammation, acquired immunity, and atherogenesis. • Thus, the stimulation of TX/endoperoxide receptors (TP) on platelets, TXA2 is a potent inducer of platelet activation.

48. Biosynthesis of Thromboxanes