Eicosanoids Prostaglandins and leucotreines Eicosanoids Prostaglandins and leucotreines

Eicosanoids Prostaglandins and leucotreines

Eicosanoids Prostaglandins and leucotreines Derivatives of the naturally occurring polyunsaturated 20 -carbon fatty acid Arachidonic acid Important mediators of inflammation Have essential physiological actions Their effects are believed to be receptor mediated

Prostaglandin Receptors http: //www. caymanchem. com/app/template/scientific. Illustrations%2 CIllustration. vm/illustration/2018/a/z

EP 4 (PGE 2) AC , [c. AMP] Small intestine, lung, thymus, kidney, uterus, pancreas, spleen, heart, stomach, brain, ileum, peripheral blood mononuclear cells FP (PGF 2) phosphoinositol turnover , [Ca 2+] Corpus luteum, uterus, stomach, kidney, heart, lung, eye, liver IP (PGI 2) AC , [c. AMP] Platelets, VSM, kidney, thymus, liver, lung, spleen, skeletal muscle, heart, pancreas TP (TXA 2) phosphoinositol turnover , [Ca 2+] Platelets, VSM, thymus, spleen,

n Synthesis: Cell membrane phospholipids NSAIDS Phospholipase A 2 Arachidonic acid Lipoxygenase Cyclooxygenase ( PG synthase ) 5 -HPESE PGD, PGH 2, PGG 2 v p LTB 4, LTC 4, LTD 4 ( SRS-A ) TXA 2 PGE 2 PGF 2α PGE 1 PGI 2

PG’s are involved in: - Inflammatory reactions - Platelet aggregation - Control of B. P ( diameter of blood vessels ) - Contraction of the uterus - Protection of the stomach and duodenum…etc n

Leukotreines are involved in: - Inflammatory reactions - Allergic reactions SRS-A ( slow reacting substance of anaphylaxis ) Believed to be a mixture of LTB 4, LTC 4, LTD 4 and is responsible for the severe bronchoconstriction in patients with anaphylaxis or bronchial asthma n

Lipooxygenase: Lungs, W. B. C’s, Platelets Cyclooxygenase ( COX ): All tissues COX 1: Stomach, Kidneys, Platelets COX 2: Other tissues Prostacyclin synthase: Blood vessels Thromboxane synthase: Platelets

n PG’s MOA: Receptor mediated PG ’s Thromboxane Prostacyclin synthase Synthase TXA 2 - PGI 2 + Adenylate cyclase Phosphodiesterase Degradation c. AMP

Inhibitors of PG synthesis: - Phospholipase A 2 inhibitors n Glucocorticoids Phenothiazines Local anesthetics Antimalarial agents

- Cyclooxygenase inhibitors * Nonselective: Block COX 1 & COX 2 NSAIDs ( Aspirin, Ibuprofen, Indomethacin, Piroxicam, Diclofenac Na+ K+, Mefenamic acid, Sulfenpyrazone, Phenybutazone, Sulindac. . etc ) * Selective: Block only COX 2 Meloxicam, Rofecoxib, Etoricoxib; Etodolac, Valdecoxib; Nabumetone…etc

- Thromboxane synthase inhibitors Dazoxiben, Hydralazine - Antagonists and inhibitors of leukotrienes synthesis: Given orally to patients with bronchial asthma and have potential use in allergy *Lipoxygenase inhibitors Zileuton *Leukotrienes antagonists Zafirlukast, Montelukast…

Major pharmacological effects to PGs: - CVS: E, I 2 → vasodilatation → ↓ B. P TXA 2 → vasoconstriction - Blood: E 1, I 2 ( prostacyclin ) → ↓ platelet aggregation TXA 2 → ↑ platelet aggregation - Bronchi: I 2, E → dilatation F → constriction - Uterus: E, F 2α strong contractors - Stomach: E, A, I 2 ↓ acid ↑ mucus n

Available PG’s, their clinical uses and dosage forms ( adm. ): - Abortifacient, labor inducers: Gemeprost ( E 1 ) vaginal pessaries Dinoprostone ( E 2 ) oral, vag. Tab. , I. V infusion Dinoprost ( F 2α ) oral, I. V infusion, intrauterine, intracervical, intraamniotic - Peptic ulcer disease Misoprostol ( E 1 ) oral n

- Antiplatelet, peripheral vascular disease, Raynaud’s disease Epoprostenol ( I 2 ), Iloprost ( I 2 ) I. V infusion - Keeping patent ductus arteriosus, impotency Alprostadil ( PGE 1 ) I. V infusion, injection into penis ( I. V ) & urethral suppositories - Postpartum hemorrhage Carboprost ( F 2α ) I. M