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Histamine and Antihistamine Drugs: Pharmacology Overview

Learn about histamine, its synthesis, receptors, effects on tissues, clinical uses, and antihistamine drugs in this comprehensive pharmacology overview.

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Histamine and Antihistamine Drugs: Pharmacology Overview

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  1. Histamine And Antihistamine Drugs Department of Pharmacology Chalapathi Institute of Pharmaceutical Sciences Guntur

  2. AUTACOIDS DEFINITION: • “Self-remedy, Referring to the Action of Local Hormones”

  3. What Are Autacoids ? • Histamine • Serotonin • Endogenous Peptides • Prostaglandins • Leukotrienes

  4. HISTAMINE • Histamine is A naturally occurring imidazole derivative • It is widely distributed in skin, GIT mucosa, lungs, brain, cerebro spinal fluid and bone marrow • It is also a component of some venoms and sting secretions

  5. Synthesis and metabolism of histamine Histidine Histamine N-methyl histamine Imidazole acetic acid Methyl imidazole acetic acid

  6. Histamine: Storage and Release Immunologic Release:  • The most important mechanism for histamine release is in response to an immunological stimulus.  • In mast cells, if sensitized by surface IgE antibodies, degranulate when exposed specific antigen.  • Degranulation means liberation of the contents of the mast cell granules, including histamine.  • Degranulationis involved in the immediate (type I) allergic reaction.

  7. Mechanical /Chemical Release: • A second type of release occurs following chemical or mechanical injury to mast cells.  • In these injuries caused degranulation • drugs like morphine,succinyl choline, d-tubocurarine , hydralazine, dextran, poly vinyl pyridone (PVP) will liberate the histamine

  8. Drugs that inhibit histamine release • β2-agonists like adrenaline,ephidrine,isoproterenol • Mast cell membrane stabilisers:disodiumcromoglycate and ketotifen

  9. Receptors & Effects • Two receptors for histamine, H1 and H2, mediate most of the well-defined actions; • H1 receptor: important in smooth muscle effects, especially those caused by IgE-mediated responses. • IP3 and DAG are released. • Bronchoconstriction and vasodilation. • Vasodilation by release of endothelium-derived relaxing factor (EDRF), are typical responses of smooth muscle. • Capillary endothelium, in addition to releasing EDRF, also contracts, opening gaps in the permeability barrier and resulting in the formation of local edema.

  10. H2 receptor: activation of adenylylcyclase → cAMP↑ • Mediates gastric acid secretion by parietal cells in the stomach. • Cardiac stimulant effect. • Reduce histamine release from mast cells a negative feedback effect. • H3 receptor: • involved mainly in presynaptic modulation of histaminergic neurotransmission in the central nervous system. • In the periphery, it appears to be a presynaptic heteroreceptor with modulatory effects on the release of other transmitters.

  11. Tissues and Organ System Effects of Histamine • Exerts powerful effects on smooth and cardiac muscle, on certain endothelial and nerve cells, and on the secretory cells of the stomach. • Sensitivity to histamine varies greatly among species - Humans, guinea pigs, dogs, and cats are quite sensitive, while mice and rats are much less so.

  12. Nervous system: • histamine is a powerful stimulant of sensory nerve endings, especially those mediating pain and itching. • Cardiovascular system: • Cardiac effects: increased contractility and increased pacemaker rate.——mediated chiefly by H2-R. But H1-R mediates the decrease of contractility in human atrial muscle. • Vascular effects: vasodilator action (H1-R, H2-R). endothelial cells contraction and increased permeability (H1-R). • Platelet function: aggregation (H1-R) anti-aggregation (H2-R)

  13. Smooth muscle: contraction (H1-R) → bronchoconstriction, abort. Histamine - induced contraction of guinea pig ileum is a standard bioassay for this amine. • Secretorytissues: stimulant of gastric acid secretion and, to a lesser extent, of gastric pepsin and intrinsic factor production. (H2-R)

  14. Clinical Uses • Pulmonary Function Testing: Histamine aerosol is sometimes used as a provocative test of bronchial hyperreactivity. • Testing Gastric Acid Secretion: However, pentagastrin is currently used for this purpose, with a much lower incidence of adverse effects. • Diagnosis of Pheochromocytoma : Histamine can cause release of catecholamine from adrenal medullary cells. This hazardous provocative test is now obsolete.

  15. Clinical uses, toxicity and contraindications of histamine • Main clinical use of histamine is as a positive control injection for skin allergy testing's ADR’S: • Flushing • Hypotension • Headache • Wheal formation • Bronchoconstriction • Gastric acidity

  16. Other Histamine Agonists • Betahistine : H1-R agonist • Impromidine : H2-R agonists • α-methylhistamine : H3-R agonists Histamine antagonists Receptor antagonists: • Selective blockade of histamine receptors (H1, H2, H3 types)

  17. H1 receptor antagonists First-generation • Highly Sedative: Diphenhydramine, Dimenhydrinate, Promethazine, Hydroxyzine • Moderately Sedative: Pheniramine, Cyproheptadine, Meclizine, Buclizine, Cinnarizine • Mild Sedative: Chlorpheniramine, Dexchlorpheniramine, Dimethindine, Triprolidine, Dimethothiazine, Trimeprazine, Mequitazine, Cyclizine, Mepyramine, Carbinoxamine Second-generation • Fexofenadine, Loratidine, Desloratidine, Cetrizine, Levocetrizine, Azelastine, Mizolastine, Ebastine, Pupatadine, Astemizole

  18. Therapeutic uses • Allergic Reactions: • Allergic rhinitis , atopic dermatitis, hay fever, urticaria • Motion sickness: • Vestibular disturbances • Sedation and hypnotics. : • these agents to be used has sleep-aids, i.e. hypnotics.  • The newer H1 antagonists by contrast, cause minimal or no sedation.

  19. Adverse effects 2nd generation: Free of CNS effects • Dryness of mouth, alteration of bowel movement, urinary hesitancy, blurring of vision (due to anticholinergic effect), Epigastric distress and headache

  20. H2 receptor antagonists • Cimetidine (Tagamet) • Ranitidine (Zantac) • Famotidine(Pepcid) • Roxatidine • Nizatidine

  21. Clinical uses • Peptic Ulcer and Duodenal Disease • Gastric Ulcer: reduce symptoms promote healing for benign gastric ulcers • GastroesophagealReflux Disorder (erosive esophagitis) Hypersecretory Disease: • Zollinger-Ellison syndrome: acid hypersecretion -- caused by gastrin-secreting tumor • Systemic mastocytosis and multiple endocrine adenomas:

  22. Adverse effects Generally well tolerated • Most common adverse effects: headache, dizziness, bowel upset, dry mouth, rashes, • CNS effects: Infrequently Confused state, restlessness, convulsion & coma – in elder with renal impairement especially with large doses infused i.v diarrhea , somnolence , , rash, thrombocytopenia , neutropenia , aplastic anemia) • Bolus i.vinj can release histamine – causes bradycardia, arrhythmias and cardiac arrest • Cimetidine (not other H2 blockers) – antiandrogenic action – Gyanacomastia, loss of libido, impotence. Temporary decrease in sperm count

  23. Interactions • Cimetidine - inhibits several CYP450 isoenzymes – inhibits metabolism of theophylline, phenytoin, carbamazepine, phenobarbitone, sulfonylureas, metronidazole, warfarin. Imipramine, lidocaine, nifedipine, quinidine • Antacids reduces absorption of all H2 blockers

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