histamine and antihistaminics

STUDY MATERIALS/ Seminar

1. Srija Bose, Sridebesh Ghorui B.Pharm , 3 rd Year , Section-A Roll No.- 18601916033,18601916034 Guru Nanak Institute Of Pharmaceutical Science And Technology HISTAMINE AND ANTIHISTAMINICS

2. CONTENTS 2 TOPIC Introduction Synthesis, Storage And Destruction Mechanisms Of Action Histamine Receptors, It’s Location Mechanisms And Their Effects H1 Receptor Antagonist H2 Receptor Antagonist Pharmacological Action Of Histamine Antagonist Pharmacokinetics Side Effects Of Antihistamine Uses Of Antihistaminic Drugs Conclusions References

3. INTRODUCTION Histamine meaning “tissue amine”( histos -tissue). Histamine =Beta-imidazolyl ethylamine Synthesised from histidine (amino acid) and degraded by oxidation and methylation Histamine is a biogenic amine found in tissues, including mast cell, basophile, lymphocytes, neurones, and gastric enterochromaffin like cell. It is an autacoid that is a molecule secreted locally to increases or decreases the activity of nearby cells. [1] 3

4. SYNTHESIS, STORAGE AND DESTRUCTION MECHANISMS OF ACTION 4 [1]

5. HISTAMINE RECEPTORS, IT’S LOCATION MECHANISMS AND THEIR EFFECTS RECEPTORS H1 Receptor H2 Receptor H3 Receptor Location and effects Blood vessel- Endothelium: releases of NO and PGI2- Vasodilation Smooth muscle of larger vessels- vasoconstriction Smooth muscle- contraction Brain- transmitter Afferent nerve ending and ganglionic cell – stimulation Heart: Atria : +ve chronotropy Ventricles : +ve inotropy Blood vessel: dilation Gastric glands: acid secretion Brain-transmitter Uterus: relaxation Brain (presynaptically): inhibition Certain blood vessel: vasodilation. Receptor types and mechanisms G q IP3, DAG G s cAMP G i/o cAMP [1,2] 5

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7. H1 RECEPTOR ANTAGONIST Highly sedative Moderately sedative Mild sedative Promethazine Diphenhydramine Pheniramine Meclizine Chlorpheniramine Clemastine [1] 7 Fexofenadine Loratadine Cetirizine Ebastine Rupatadine [1]

8. H2 RECEPTOR ANTAGONIST 8 The pharmacological and clinical utility of H2 antagonist for inhibition of gastric acid secretion in the treatment of GI disorder . cimetidine ranitidine famotidine Nizatidine [2]

9. 9 1 st Generation Antagonism of histamine: block the histamine induced- vasoconstriction Causes low BP Antiallergic: Hypersensitivity are suppressed CNS: cause sedation because they penetrate BBB Anticholinergic: H1 blocker antagonise muscarinic action of acetylcholine. 2 nd Generation absence of CNS depressant. Higher selectivity towards H1 receptors. No anticholinergic side effects. Additional anticholinergic activity, apart from histamine blocked. Inhibit late phase allergic reaction by modifying the action of leukotrienes, PAF (platelet activating factor), cytokines, etc. Heart: Atria: + ve chronotropy Ventricles: + ve inotropy BV - constriction Gastric gland- histamine released by enterochromaffin cells in stomach is blocked from binding on parietal cell H2 receptors. [1]

10. PHARMACOKINETICS ABSORPTION DISTRIBUTION METABOLISM EXCRETION H1 antagonist are well absorbed from oral and parenteral routes. Following oral administration, the peak plasma concentration is achieved in 1-3 hour and effect usually last for 4-6 hours for 1 st generation drugs. For 2 nd generation drugs effect last for 12-24 hours. This agents distributed widely through out the body including CNS for 1 st generation agents. The newer compounds penetrate brain poorly. H1 antagonists are metabolised by CYPs(Cytochrome P450 system) in the liver. The plasma concentration of active or inactive metabolised of H1 antagonists depends on CYP system activity. Only acrivastine , cetirizine, levocetirizine, fexofenadine, desloratadine prevent this metabolic pathway to a relevant extent which makes them more predictable regarding their desirable effects. These are excreted unchanged in the urine. Exceptions are – Fexofenadine- excreted through faeces Epinastine - excreted through both urine and faeces. [2] 10

11. SIDE EFFECT OF ANTIHISTAMINE H1 ANTIHISTAMINE 1 st generation 2 nd generation Sedation Diminished alertness and concentration Fatigue Restless, nervous, unable to sleep Dryness of mouth Alternation of bowl movement Blurred vision Teratogenic in animals Eg : Hydroxyzine, Cyclizine Drowsiness Fatigue Headache Nausea Dry mouth H2 ANTIHISTAMINE Constipation Diarrhoea Difficulty sleeping Dry mouth and skin Headache Ringing in ear A runny nose Trouble urinating [1] 11

12. USES OF ANTIHISTAMINE DRUGS Allergic disorder: Antihistamines do not suppress AG: AB reaction, but block the effects of released histamine—are only palliative. They effectively control certain immediate type of allergies, e.g. itching, urticaria, seasonal hay fever, allergic conjunctivitis and angioedema of lips, eyelids, etc. Motion sickness: Promethazine, diphenhydramine, dimenhydrinate and meclozine have prophylactic value in milder types of motion sickness; Vertigo: Cetirizine is the H1 anti histamine having additional anticholinergic, anti-5-HT, sedative and vasodilator properties which has been widely used in vertigo. Parkinsonism: Promethazine and some other afford mild symptomatic relief in early cases – based on anticholinergic property. Sedative, Hypnotic, anxiolytic: Antihistamines with CNS depressant action have been used as sedative and to induce sleep, especially in children. Common cold: Antihistamines do not affect the course of the illness but may afford symptomatic relief by anticholinergic (reduce rhinorrhoea) and sedative actions. The newer non sedating antihistamines are less effective in this respect .[1] 12

13. CONCLUSION Histamine is an important chemical messenger that exhibits significant physiological effects mediated through its receptors. A through knowledge of drugs is very much useful to treat the clinical conditions arising due to imbalance of histamine in the body .[1] Drugs with antihistamine action are the most commonly prescribed medication in daily dermatological practice, both adults and children. H1 receptors act on the gene transcription of inflammatory mediators. H2 antagonist are practically non-sedative because its not permeable through BBB. When a person has a problem in metabolising and breaking down histamine, it's level build up and lead to worrying symptoms like rashes, itching, swelling, redness etc. [2] All who have histamine intolerance in any kind need to take steps and manage it by taking specific diets and supplements – Protein- Dairy products, egg whites, peanuts Vegetables - Tomatoes (Red one has higher histamine than white or yellow one), spinach, pumpkin etc 13

14. REFERENCE TRIPATHI KD “ Essentials Of Medical Pharmacology ”, Seventh Edition, Jaypee Brothers Medical Publishers, 2013, Chapter 11 “Histamine And Antihistaminics”, Page No- 159-169, ISBN: 978-93-5025-937-5 Brunton Laurence L. “Goodman & Gilman’s The Pharmacological Basis Of Therapeutics ”, 13 th Edition ,Mc Graw Hill Education, Chapter 39 “Histamine, bradykinin& Their Antagonists” Page no.- 713& 719,ISBN-978-1-25-958474-9. photo_51686184_stock-vector-histamine-receptor-function-target-tissue-and-organs-histamine-action 14 Histamine receptor. Function, target tissue and organs. Histamine action               

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