Prostaglandin and it's pharmacological role

by THakur prasad singha

1. PROSTAGLANDIN AND IT’S PHARMACOLOGICAL ROLE BY THAKUR PRASAD SINGHA 3 RD YEAR, 6 TH SEM ROLL.NO. – 20801914097 BHARAT TECHNOLOGY

2. INTRODUCTION The name ‘prostaglandin’ derives from the prostate gland. Prostaglandin was first discovered and isolated from human semen in 1930s by U LF VON EULER. Structure of prostaglandin is proposed by Bergstrom in (1950). Prostaglandin and related compounds (like as leukotrienes) collectively known as eicosanoids. Most are produced from arachidonic acid, a 20 carbon polyunsaturated fatty acid. The eicosanoids are considered “local hormone”. They have specific effects on targets cells close with there site of formation. They are rapidly degraded, s o they are not transported with distal site within the body.

3. CHEMISTRY Prostaglandin has a five membered ring and two side chains projecting in opposite direction at right angel to the plane of the ring. There are many series of PGs and thromboxanes (TXs) designated A,B,C……I, depending on the ring structure and the substituents on it. Each series has number of double bonds in the side chains.

4. PGD 2 STRUCTURE:

5. BIOSYNTHESIS OF PGs :- Cyclooxygenase Lipoxygenase H 2 O CYCLIC ENDOPEROXIDES CELL MEMBRANE PHOSPHOLIPIDS ARACHIDONIC ACID PGG 2 PGH 2 ISOMERASES THROMBOXANE SYNTHASE PROSTACYCLIN SYNTHASE PGE 2 PGD 2 PGF 2 TX A 2 PHI 2 HPETE LTA 4 LTC 4 LTD 4 LTE 4 LTB 4

6. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 BLOOD VESSELS VD→ ↓ BP VD→ ~ BP ( LARGE VEINS CONTRACTS) VD→ ↓↓↓ BP VC PG endoperoxides (G2 and H2) are inherently vasoconstrictor , but often produce vasodilatation or a biphasic response due to rapid conversion to other PGs, especially PGI2, in the blood vessels themselves. PHARMACOLOGICAL ROLES OF PG S

7. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 PLATELETS ANTI- AGGREGATORY PRO-AGGREGATORY TXA2 produced by platelets and PGI2 produced by vascular endothelium probably constitute a mutually antagonistic system .

8. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 UTERUS IN VIVO-CONTRACTION IN VITRO- RELAXATION SOFTENING OF CERVIX IN VIVO & IN VITRO-CONTRACTION SOFTENING OF CERVIX - - Clinical role: PGs mediate initiation and progression of labour. Aspirin has been found to delay the initiation of labour and also prolongs its duration. PGs  uncoordinated uterine contractions compress blood vessels  uterine ischemia  pain (Dysmenorrhoea). Aspirin is highly effective treatment.

9. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 KIDNEY NATRIURESIS ↓CL-REABSORPTION INHIBIT ADH ACTION→DIURESIS RENIN RELEASE - NATRIURESIS VD RENIN RELEASE VC PGs appear to function as intra-renal regulators of blood flow as well as tubular reabsorption in kidney. The NSAIDs tend to retain salt and water. Bartter's syndrome, characterized by decreased sensitivity to angiotensin II is associated with i ncreased PG production. Many of the manifestations are improved by prolonged use of NSAIDs.

10. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 BRONCHI DILATATION CONSTRICTION MILD DILATATION CONSTRICTION Asthmatics are more sensitive to constrictor as well as dilator effects of PGs. Clinical Role: Aspirin induces asthma.

11. ORGAN PGE 2 PGF 2 α PGI 2 TXA 2 STOMACH ↓ ACID SECRETION ↑ MUCOUS PRODUCTION - ↓ ACID SECRETION(WEAK) MUCOSAL VD - INTESTINE ↑PERISTALSIS ↑ Cl − & WATER SECRETION SPASMOGENIC WEAK SPASMOGENIC WEAK SPASMOGENIC NSAIDS can induce gastric ulcer due to loss of this function by COX-1 inhibition . Clinical role :

12. USES OF PGs ANALOGUES: ABORTION INDUCTION OF LABOUR POSTPARTUM HAPMORRHAGE PEPTIC ULCER GLAUCOMA TO AVOID PLATELET DAMAGE CANCER PULMONARY HYPERTENSION

13. REFERENCES :- Tripathi KD. Essential of Medical pharmacology . 7 th edition. Jaypee Brothers Medical Publishers (P) Limited; 2013:181-191 Udaykumer P. Textbook of Medical Pharmacology . 2 nd edition. CBS Publishers & Distributors PVT.LTD; 2010: 274-277 Satyanarayana U; Chakrapani U; Biochemistry . 4 th edition, 2014. Published by – Elsevier Health Science; 644-649 Lippincott Williams & Wilkins. Illustrated reviews Pharmacology . 5 th edition, 2012. Published By Wolters Kluwer; 549-554

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