Histamine and antihistaminic

Histamine and Antihistaminics

1. Autacoids (Histamine & Antihistamine) Dr Naser Ashraf Tadvi 1

2. Case study A 24-year-old male, John develops a runny nose, itchy eyes, and sneezing every winter. To relieve his symptoms, he takes an OTC antihistamine John is annoyed by the unpleasant effects that accompany his allergy medication. Every time he takes this antihistamine, he feels drowsy and his mouth feels dry. He makes an appointment with his doctor who, advises him to take loratadine . Upon taking new allergy medication, his symptoms are relieved, and he experiences no drowsiness or other adverse effects.

3. Questions What Is Johns Problem Which OTC is probably John taking? What is the reason of drowsiness and dryness of mouth in John ? What is loratadine?Why did Physician prescribe it for John?

4. Objectives Describe the pharmacology of histamine & enumerate its related drugs. Classify Histamine-1(H1) antagonists. Discuss the pharmacology of H1 Antihistaminics with emphasis on clinical uses, adverse drug reactions & interactions 4

5. What are Autacoids Autos = self; Akos = remedy ( Greek ). Secreted locally to increase or decrease the activity of nearby cells. Includes Amine autocoids : Histamine, Serotonin Lipid derived: Prostaglandins and Leukotrines Peptides: Bradykinin, angiotensin Others: Cytokines 5

6. Histamine Histos : Tissue Present mostly in mast cells: skin, lungs, GIT Mucosa Non mast cell histamine: Brain, Gastric Mucosa Histamine is a biogenic amine present in many animal and plant tissues .

7. Synthesis of histamine Synthesized by decarboxylation of amino acid histidine

8. Release of histamine Immunologic (Type 1 reaction) Chemical/ Mechanical release Morphine Succinylcholine D tubocurarine Dextran

9. 9 Release of histamine

10. Histamine Receptors Histamine H 1 Receptors H 2 Receptors H 3 Receptors (presynaptic auto receptors) ↑ Ca2+ Smooth muscle contraction ↑ capillary permeability Vasodilation Sensory nerve endings pain & itching ↑ cAMP ↑ Gastric acid secretion Blood vessels: vasodilation Increased capillary permeability ↓ histamine release ↓secretion Vasodilation ↓ cAMP Smooth muscle, vascular endothelium, brain Gastric parietal cells, cardiac muscle, Brain Heart CNS and some peripheral nerves. H 4 Receptors ↓ cAMP Hematopoietic cells, gastric mucosa.

11. Actions of histamine (H1) Tissues Effects Peripheral nerves Sensitization of afferent nerve terminals Smooth muscles Bronchoconstriction Intestine: contraction Exocrine glands Increased secretions Hypothalamus, mid brain Wakefulness 11

12. Actions of Histamine (H1 & H2) Arterioles and post capillary venules Dilatation and decreased BP Increased capillary permeability Heart: increased HR and Force of contraction Triple response Severe hypersensitivity reaction

13. Actions of histamine (contd.) Tissue Effects Clinical manifestations Receptor subtype Stomach Increased gastric acid secretion Peptic ulcer disease, heartburn H2 CNS Decreased release of Histamine/ NE - H3 (Auto-receptor) 13

14. Adverse effects of histamine release Itching, Urticaria Flushing Hypotension Tachycardia Bronchospasm Angioedema Wakefullness Increased acidity (Gastric acid secretion)

15. Betahistine H1 Selective histamine analog Use: Vertigo of Meniere`s Disease Acts by Vasodilation in inner ear Contraindication Asthmatics Peptic Ulcer

16. Classification of antihistaminics First Generation Diphenhydramine Dimenhydrinate Doxylamine Promethazine Hydroxyzine Pheniramine Cyroheptadine Meclizine Chlorpheniramine Dexchlorpheniramine Second Generation Cetirizine Levocetirizine Fexofenadine Loratidine Desloratidine Ebastine Astemizole Acrivastine

17. H1-Antihistaminics /First generation

18. H1-Antinistaminics /second generation

19. Therapeutic uses Allergic diseases Rhinitis, urticaria, conjunctivitis. Atopic dermatitis Bronchial asthma Anaphylaxis Antiemetics, motion sickness, morning sickness Insomnia Preanaesthetic medication Cough Parkinsonism Vertigo Acute Muscle dystonia 19

20. As Antiemetic: Hydroxyzine, promethazine Motion sickness and Vestibular disturbances first generation antihistamines like Diphenhydramine and Promethazine are useful Cyclizine and Meclizine- less sedative Morning sickness: Doxylamine 20 Therapeutic uses

21. Uses: second Generation Antihistamines Allergies Reduce symptoms of itching, sneezing, rhinorrhea and allergic conjunctivitis 21 Topical preparations- Azelastine Olopatadine

22. Common Adverse Effects & Contraindications Adverse effects: Anticholinergic adverse effects like blurred vision, dry mouth, tachycardia, urinary retention, dizziness, drowsiness Paradoxical excitement in infants and children Overdose of Astemizole and Terfenadine may cause arrhythmias Contraindications : Acute angle-closure glaucoma, Hypersensitivity, Urinary obstruction

23. Drug interactions Terfenadine and astemizole Ketoconazole Macrolide antibiotics Lethal ventricular arrhythmias. Withdrawn from market Grapefruit juice also inhibits CYP3A4. Increased levels of antihistamines. 23

24. Mechanism of action Competitive antagonism Histamine General formula of H1 Blocker

25. Second generation H 1 Blockers (Non Sedative:Less anticholinergic property) Fexofenadine Astemizole Loratidine Cetrizine Levocetrizine Azelastine Terfenadine Uses: Allergic rhinitis Allergic Dermatitis Allergic conjunctivitis Urticaria Common cold

26. Advantages of second generation antihistaminics They have no anticholinergic side effects Do not cross blood brain barrier (BBB), hence cause minimal or no drowsiness and sedation Do not impair Psychomotor performance

27. Summary Histamine Antihistaminics First generation Second generation