Seminar on histamine

pathological and physiological role of histamine

1. SEMINAR ON HISTAMINE Under the guidance of Presented by Prof .Mrs . Santhrani Thakur Deepika Darnasi , M.Pharm , Ph.D l/ ll M. pharmacy, Dept. of pharmacology

2. CONTENTS INTRODUCTION TYPES OF AUTOCOIDS LOCATION SYNTHESIS METABOLISM HISTAMINIC RECEPTORS PATHOLOGICAL AND PHYSIOLOGICAL ROLE PHARMACOLOGICAL ACTIONS THERAPEUTIC USES

3. INTRODUCTION HISTAMINE: Amine autocoid . Autocoid (Greek word) autos - self akos - remedy/self healing substances Secreted from special cells (endothelial cells or tissues) & transported through the circulatory system to act either locally (at the site of synthesis or release) or on distant target tissues.

4. TYPES OF AUTOCOIDS AMINE AUTOCOIDS : Histamine 5-HT PEPTIDE AUTOCOIDS : Angiotensin Plasma Kinnins Somatostatin PHOSPHALIPID DERIVED AUTOCOIDS : Eicosanoids(leukotrienes, PG,Thromboxanes ) Platelet activating factor

5. LOCATION Uneven distribution throughout the body. Mostly within storage granules of mast cells (inactive complex) & WBC (basophils and eosinophils). Tissues rich -skin, gastric & intestinal mucosa ,Lungs, liver, placenta. Occurs in brain ,epidermis, growing region. Tissue fluids minor- blood, plasma, body secretions, venom,pathological fluids.

6. Synthesis Beta - imidazolyl ethylamine,derivative of imidazole .

7. METABOLISM OF HISTAMINE Histidine histidine decarboxylase Histamine N-methyl transferase N- methyl histamine diamine oxidase oxidase Methyl imidazole acetic acid Imidazole acetic acid

8. HISTAMINIC RECEPTORS HISTAMIN E RECEPTOR H1 RECEPTOR H2 RECEPTOR H3 RECEPTOR H4 RECEPTOR Receptor type GPCR GPCR GPCR GPCR Location Intestinal, bronchial, uterine smooth muscles, CNS, endothelial cells, sensory nerve endings On parietal cells of GIT, Blood vessels, heart, brain On brain, lungs, spleen, skin, gastric mucosa, certain blood vessels On thymus gland, small Intestine, spleen, colon, Bone marrow, Present on surace of basophils

9. Histamine receptor H 1 receptor H 2 receptor H3 receptor H 4 receptor Specific agonist 2 methyl histamine, 2 thiazolyl etylamine , 2 pyridyl etylamine Dimaprit Impromidine 4 –methy l histamine α - Methyl histamine Imetit Clozapine Specific antagonist Chlorpheniramine , Mepyramine Rantidine , cimetidine Thioperamide , Clobenpropit burimamide thioperamide

10. HISTAMINE RECEPTOR H1 RECEPTOR H2 RECEPTOR H3 RECEPTOR H4 RECEPTOR Mechanism of action Hydrolysis of PIP2 Increases IP3 and DAG levels Increase in CAMP Levels Decrease in CAMP and calcium levels Decrease in the levels of CAMP and calcium influx Release of intracellular calcium levels Causes opening of potassium channels Phosporylation of proteins Activation of protein kinase c

11. PHARMACOLOGICAL ACTIONS OF RECEPTORS H1 RECEPTORS Contraction of smooth muscles Vasodilation of blood vessels Increase in capillary permeability H 3 RECEPTORS Vasodilation of blood vessels Decreases neurotransmitter release H 2 RECEPTORS Increases gastric secretion from gastric glands Vasodilation of blood vessels Relaxation of uterine smooth muscles Positive inotropic and chronotropic effects on heart H 4 RECEPTORS Causes chemotaxis of WBC

12. PATHOPHYSIOLOGICAL ROLE PATHOLOGICAL ROLE In Hypersensitivity reactions In Inflammation PHYSIOLOGICAL ROLE Gastric secretion Neuronal Transmission Tissue growth and repair

13. IN HYPERSENSITIVITY REACTIONS

14. HISTAMINE RESPONSIBLE : Utricaria (skin rashes) angioedema (swelling of tongue ,lips, eyes) Bronchoconstriction Anaphylactic shock

15. INFLAMMATION .Histamine – mediator of vasodilation and changes that occur during inflammation.

16. INFLAMMATON PROCESS

17. DIAGRAM OTHER VIEW

18. GASTRIC ACID SECRETION DIAGRAM

19. Secretion of Hcl by gastric parietal cell

20. IN NEURONAL TRANSMISSION

21. TISSUE GROWTH AND REPAIR Histamine-tissue amine,as tissues contain high concentrations of histamine ,plays role in growth and regeneration of tissues. Treats or prevents breast cancer. Blood merges with cholesterol and forms DDA ( Dendrogenin A) A compound with anti-tumour p roperties

22. PHARMACOLOGICAL ACTIONS On blood vessels: Dilates of pulmonary vessels, Dilates cerebal blood vessels, H1-vasodilation-SHORT H2-Vasodilation in smooth muscles ( PROLONGED) Intradermal injection–TRIPLE RESPONSE: Flush/red reaction , Wheal ,Flare

23. On heart: H2-Positive chronotropic and inotropic effect. H1-decrease AV conduction On smooth muscles: H1-stimulant effect on smooth muscles. contraction of smooth muscles causing bronchoconstriction and increased motility of intestinal mucosa. On gastric glands:H2 On CNS On ganglionic cells

24. THERAPEUTIC USES Diagnostic purposes. positive control injection in skin hyper reactivity testing. Test acid secreting capacity of stomach. Clinical diagnosis of pheochromocytoma .

25. REFERENCES ESSENTIALS OF MEDICAL PHARMACOLOGY, 6 th Edition ,K D Tripathi . THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, Goodman and Gilman’s, 12 th Edition. RANG AND DALE ,www.wikipedia.org

26. THANK YOU