Histamine

research scholar

1. Presentation on Histamine Presented by: Presented to: Rabiya Ahsan Dr. Badruddin (research scholar) associate professor(Jr .) Integral University Lucknow 2020-2021

2. Introduction First Autacoid to be discovered. (Greek: autos=self; akos =cure) Synthesized in 1907 • Isolated and demonstrated to be a natural constituent of mammalian tissues (1927); hence the name Histos =Tissue • H1 was discovered in1966 • H2 in1972 • H3 in1987 • H4 in 2001 Definition:- Chemical messenger that mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in parts of the brain. Plays an important role in gastric acid secretion.

3. Synthesis , storage and release Synthesized by decarboxylation of amino acid histidine . Histamine is present in storage granules of mast cells & also found in skin, lungs, liver, gastric mucosa etc . Histamine is released by several mechanism. Immunological release Chemical and mechanical release Loss of granules from mast cells also release histamine since sodium ions in the extracellular fluids rapidly displace histamine from the complex.

4. Mechanism of histamine Histamine H1 Receptor H2 Receptor H3 Receptor Increase Ca 2+ Decreased c AMP increased cAMP Smooth muscle contraction. Increased capillary. Permeability. Vasodilation. Sensory nerve ending pain & itching Increased gastric acid secretion Blood vessels Vasodilation Increased capillary permeability Decreased histamine release Decreased secretion vasodilation

5. HISTAMINE (Pharmacological Effects/ biological function) Cardiovascular system. vasodilation Smooth muscle of bronchioles; contraction of nonvascular smooth muscle. Peripheral Nervous system: itching and pain Exocrine Glands Gastric glands Salivary glands Sweat glands Secretion Pancreas Bronchial glands Lacrimal glands secretion

6. Histamine action through its receptors Types Location Effect Treatment H1 Throughout body (smooth muscles, heart, CNS) Bronchoconstriction, vasodilation, pain, motion sickness Allergies, nausea, sleep disorder H2 Specific location in the body (gastric parietal cell, vascular smooth muscle, CNS, heart, uterus Regulate gastric acid secretion, vasodilators Stomach ulcers H3 CNS, small intestine Neural presynaptic receptor, may function to release histamine unknown H4 Spleen, thymus, leukocytes Mast cell chemotaxis Treatment of autoimmune diseases like rheumatoid arthritis

7. Anti-histaminic agents Anti-histaminic agents usually referred to those opposing the H1 mediated effects of histamine. These are classified as: First generation Second generation Those opposing the H2 mediated effect of histamine are known as anti-secretory agents.

8. H1-RECEPTOR ANTAGONISTS (Conventional Antihistaminics ) First generation Antihistaminics Highly sedative: Diphenhydramine Dimenhydrinate Promethazine Hydroxyzine Moderately sedative: Pheniramine Cyproheptadine Meclizine Buclizine Cinnarazine Mild sedative: Chlorpheniramine , Dexchlorpheniramine , Dimethindene , Triprolidine , Mebhydroline , Cyclizine , Clemastine

9. Uses: Adjunctive in anaphylaxis and other cases where histamine release can occur. Antiallergy Prevent motion sickness/antiemetic Antitussive ADR Sedation, dizziness, fatigue and antimuscranic effects (dry mouth, constipation, urinary retention, blurred vision)

10. Second generation Antihistaminics : Fexofenadine, Loratadine , Desloratadine , Cetrizine , Levocetrizine , Azelastine , Mizolastine , Ebastine , Rupatadine . Uses: Pruritus, allergic rhinitis, urticaria ADR Fatigue, dry mouth, pharyngitis, dizziness and arrhythmia

11. H2 antihistaminics Cimetidine Ranitidine Famotidine Roxatidine Primarily used in peptic ulcer and other gastric hypersecretory states H3 antihistaminics : Thioperamide No clinical utility. Mast cell stabilisers (histamine release inhibitors) Cromolyn and nedocromil . Dual acting antihistamines (H1 antihistaminic action + mast cell stabilisers) Azelastine and kitotifen .

12. Treatment of peptic ulcers/other gastric conditions Peptic ulcer disease causes can be Hypersecretion of acid and pepsin Infection due to helicobacter pylori Other risk factors NSAID’s like aspirin, ibuprofen etc Cigarette smoking, alcohol consumption, oily and spicy diet Emotional stress Treatment includes A ntacids: aluminium and magnesium hydroxide, NaHCO 3

13. H2 histamine receptor antagonist- ranitidine Protective mucosal barriers- sucralfate , carbenoxolone PPIs- omeparazole , pantoparazole Prostaglandins -misoprostol Muscarinic antagonists- pirenzipine Along with antibiotics- if infection with H- pylori

14. Reference JOHN H.BLOCK & JOHN M WILSON& GISVOLD’S Organic Medicinal & Pharmaceutical chemistry. ( Pg ): 698 – 728 D.SRIRAM & P.YOGEESWARI -Medicinal chemistry. ( Pg ): 278 – 302 BERTRAM G.KATZUNG, SUSAN B.MARTERS ANTHONY J.TREVOR Basic & Clinical pharmacology ( Pg ) : 277 K.D TRIPATHI Essentials of medical pharmacology. ( Pg ): 159 – 160.