histamine and antihistaminics

histamine and antihistaminics

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  Srija Bose, SridebeshGhorui B.Pharm, 3rd Year , Section-A Roll No.- 18601916033,18601916034 Guru Nanak Institute Of Pharmaceutical Science And Technology HISTAMINE AND ANTIHISTAMINICS
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  CONTENTS 2 TOPIC Introduction Synthesis, Storage AndDestruction 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
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  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
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  SYNTHESIS, STORAGE AND DESTRUCTIONMECHANISMS OF ACTION 4 [1]
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  HISTAMINE RECEPTORS, IT’SLOCATION MECHANISMS AND THEIR EFFECTS RECEPTORS H1 Receptor H2 Receptor H3 Receptor Location and effects • Blood vessel- 1. Endothelium: releases of NO and PGI2- Vasodilation 2. 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 Gq IP3, DAG Gs cAMP Gi/o cAMP [1,2] 5
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  6 HISTAMINE RECEPTORS [3]
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  H1 RECEPTOR ANTAGONIST Highlysedative Moderately sedative Mild sedative • Promethazine • Diphenhydramine • Pheniramine • Meclizine • Chlorpheniramine • Clemastine [1] 7 1st generation Sedation (penetrate BBB) They interact with other receptors producing variety of adverse effects 2nd generation They are made polar by the addition of carboxyl groups, so they can't penetrate BBB and show less sedation. They are specific for peripheral H1 receptor • Fexofenadine • Loratadine • Cetirizine • Ebastine • Rupatadine [1]
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  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]
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  Pharmacological Action OfHistamine Antagonist H1 receptors H2 receptors 9 1st 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. 2nd 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]
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  PHARMACOKINETICS ABSORPTION DISTRIBUTION METABOLISMEXCRETION • 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 1st generation drugs. • For 2nd generation drugs effect last for 12-24 hours. • This agents distributed widely through out the body including CNS for 1st 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
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  SIDE EFFECT OFANTIHISTAMINE H1 ANTIHISTAMINE 1st generation 2nd 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
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  USES OF ANTIHISTAMINEDRUGS • 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
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  CONCLUSION • Histamine isan 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
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  REFERENCE 1. 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 2. Brunton Laurence L. “Goodman & Gilman’s The Pharmacological Basis Of Therapeutics”, 13th Edition ,Mc Graw Hill Education, Chapter 39 “Histamine, bradykinin& Their Antagonists” Page no.- 713& 719,ISBN-978-1-25-958474-9. 3. photo_51686184_stock-vector-histamine-receptor-function-target-tissue-and-organs-histamine- action 14
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