1. HISTAMINE

2. Storage Sites Highest amounts in mast cells BasophilsSkinLung Intestinal mucosa StomachBrain

3. RELEASE

4. Rlease  Primary mechanism during allergic reactions IgE antibody interacts with antigen on the surface of mast cells  Enzymes as trypsin or drugs as morphine liberate histamine without prior sensitization  Inhibition of release with β 2 agonists

5. SYNTHESIS & INACTIVATIONTION

6. H 2 H 1 H 3 H istamine Mediator Neurotransmitter CNS ANS H 3 + + + H 1 -ve presynaptic autoregulation

7. Receptor Type Major Tissue Locations Major Biologic Effects H1H1 smooth muscle, endothelial cells acute allergic responses H2H2 gastric parietal cellssecretion of gastric acid H3H3 central nervous systemmodulating neurotransmission H4H4 mast cells, eosinophils, T cells regulating immune responses Histamine receptors

8. Histamine receptors antagonists

9. Diphenhydramin ( First generation) Diphenhydramin ( First generation) Clinical uses : Insomnia Motion sickness H 1 antagonists

10. Loratadine (Second generation) Loratadine (Second generation) Non-sedating Clinical uses Allergic conditions : allergic rhinitis Conjunctivitis Urticaria H 1 antagonists

11. Cimetidine Cimetidine Inhibitor of gastric acid secretion Used in the treatment of : peptic ulcers H 2 antagonists

12. BETAHISTINE Used in treatment of : vertigo in middle ear H 3 antagonists

13. EICOSANOIDS

15. INHIBITORS OF EICOSANOIDS

16. Phospholipids Phospholipase A 2 Arachidonic Acid Prostaglandins PGE2, PGD2, PGF2  Thromboxane (TXA2) Prostacyclin (PGI2) COX1 & COX2 Leukotrienes LTA4, B4, D4, C4 Lipoxygenase Drugs NSAIDs Corticosteroids Zileuton

17. ACTIONS

18. Vascular smooth muscles: Potent vasoconstrictor. PGE 2 and PGI 2 Thromboxane A 2 Potent vasodilators.

19. Blood: PGE 2 and PGI 2 inhibit platelet aggregation TXA2 a potent inducer of platelet aggregation.

20.  One of the chemical mediators in inflammatory reactions. Inflammation:

21. -PGF 2  -LTs and thromboxane are potent bronchoconstrictors in man → allergic bronchospasm. Bronchial smooth muscle: - PGE 2 cause dilatation.

22. Uterine smooth muscle: PGE 2 and PGF 2  → Menstruation/ Dysmenorrhea/ Labor contractions

23. - PGE 2 and PGF 2  and LTs GIT smooth muscle:  GIT motility

24. GIT secretions: PGE 2, PGE 1 PGI 2 ↓ acid and pepsinogen secretion.  mucin, water and bicarbonate & Blood flow.

25. PGE2 and PGI2 increase renal blood flow and diuresis. Kideny

26. Central and peripheral nervous systems  Fever: PGE 1 and PGE 2 increase body temperature.

27. CLINICAL USES OF PGS ANALOGS

28. Carboprost PGF 2 α ( analog) 1)Abortifacient: Trigger abortion in first trimester.

29. 2) For postpartum haemorrhage vasoconstriction + uterine muscle contraction

30. (PGF 2 α analog ) eye drops in open angle glaucoma. ↓ IOP by enhancing outflow of the aqueous humar. Latanoprost

31. Alprostadil (PGE 1 analog) 1- Injected in corpus cavernosum of the penis for some forms of male impotence.

32. 2- In congenital heart anomalies to keep the patent ductus arteriosus until surgery.

33. Misoprostol  (PGE 1 analog) Peptic ulcer

34. Thank you