Antihistamines

Useful for B.Sc(N) second year Pharmacology subject

1. Antihistamines Mr.Visanth V S Asso.Professor IGSCON, Amethi

2. A chemical messenger mostly generated in mast cells. Histamine is present in practically all tissues, with significant amounts in the lungs, skin, blood vessels, and GI tract Also found in venoms of bees, wasps and other stinging secretions. Found at high concentration in mast cells and basophils Histamine

3. Mediates a wide range of cellular responses Allergic and inflammatory reactions Gastric acid secretion Bronchospasm Stimulates nerve ending causing pain and itching Neurotransmission in parts of the brain Actions of histamine

4. Most often, histamine is just one of several chemical mediators released in response to stimuli The stimuli for release of histamine from tissues may include destruction of cells as a result of cold, toxins from organisms, venoms from insects and spiders, and trauma Allergies and anaphylaxis can also trigger significant release of histamine. Release of Histamine

5. Antihistamines are histamine antagonists. They can be H 1 receptor blockers and H 2 receptor blockers. Drugs that block H 1 receptor blockers are conventionally called antihistamines. H 2 blockers are used in the treatment of peptic ulcer. Antihistamines

6. Sedatives Diphenhydramine Dimenhydrinate Promethazine Chlorpheniramine Cyclizine Meclizine M epyramine Tripelennamine Classification of H 1 Blockers Non-sedatives Fexofenadine Astemizole Loratidine Ceterizine

7. H1-receptor blockers are well absorbed after oral administration, with maximum serum levels occurring at 1 to 2 hours First-generation H1- receptor blockers are distributed in all tissues, including CNS Most are metabolized in liver and excreted unchanged in urine Fexofenadine is excreted largely unchanged in feces Some are available as ophthalmic or intranasal formulations Pharmacokinetics

8. Blockade of actions of histamine Block the actions of histamine on H1 receptors. They block the histamine induced effects on smooth muscles of the gut, bronchi, blood vessels and triple response on skin. Sedation Cause drowsiness, dizziness and inability to concentrate. The degree of sedation varies from one drug to another Actions

9. Antimotion sickness effects Several antihistamines prevent motion sickness and vomiting due to other labyrinthine disturbances. Some of them also control vomiting of pregnancy. Anticholinergic actions Antiparkinsonian effects Like orphenadrine, diphenhydramine and promethazine suppress tremors, rigidity and sialorrhea in parkinsonism due to their anticholinergic property

10. Sedation Dizziness Motor incoordination Inability to concentrate Dry mouth Blurred vision Adverse Reactions Constipation Urinary retention Epigastric distress Headache Many of them are teratogenic

11. Also called II generation antihistamines No sedation because they poorly cross BBB No anticholinergic side effect Newer Non Sedative Antihistamines

12. Allergic reactions Allergic rhinitis Conjunctivitis Hay fever Urticaria Pruritis Allergic skin rashes Pollinosis Uses

13. Common cold Motion sickness Prevents motion sickness Vertigo and vestibular disturbances Antiemetic Promethazine is used in drug induced post operative vomiting and morning sickness Preanesthetic medication For producing sedative, anticholinergic and antiemetic property. Uses- Contd….

14. Hypnotic Sometimes used to induce sleep. Hydroxyzine has been used as an anxiolytic Parkinsonism Diphenhydramine, orphenadrine and promethazine are useful for this due to their anticholinergic property Cough Due to postnasal drip can be controlled by diphenhydramine

15. Dosage Drug Trade Name Dosage Diphenhydramine Benadryl cap, syr 25-50mg oral, Promethazine Phenergan tab, syr , inj 25-50 mg oral Pheneramine maleate Avil tab, syr , inj 25-50 mg oral Chlorpheniramine ZEET tab, syr , inj 4-20 mg oral Cyclizine Marezine tab 50mg oral Cetirizine Alerid tab, syr 10mg oral Fexofenadine Allegra tab 180mg oral

16. H 2 - Receptor A ntagonists H2-receptors stimulate gastric acid secretion and are also present in human heart, blood vessels and uterus (and probably brain). There are a number of competitive H 2 -receptor antagonists in clinical use, which include cimetidine and ranitidine. The uses of these are similar and will be considered together in this section.

17. Mechanism of action Competitive inhibition of H2 receptors - Inhibits gastric acid secretion (60-70 %). They inhibit gastric acid secretion by inhibiting the action of histamine and histamine 2 receptors in gastric parietal cells.

18. Pharmacokinetics Rapidly and absorbed well. Cimetidine acts for 5-8 hrs, ranitidine and famotidine for 12 hrs. They are partly metabolized in the liver and excreted by kidneys.

19. Adverse Effects They are well tolerated with minor side effects like; Diarrhea Dizziness Muscle pain Headache

20. Cimetidine H as antiandrogenic effect It increases plasma prolactin level and inhibits estrogen metabolism in liver. On prolonged use Gynaecomastia I mpotence – men Menstrual irregularities Galactorrhea – women

21. Ranitidine Ranitidine is well absorbed after oral administration. More potent, longer acting, has no antiandrogenic effects.

22. Therapeutic Uses Peptic ulcer : Gastric and Duodenal ulcer Gastroesophageal reflux disease ( GERD) Stress ulcers and Gastritis Indigestion

23. Dosage Drug Dosage & Frequency Ranitidine 150mg BD/300mg HS Cimetidine 400mg BD Famotidine 20mg BD Roxatidine 75mg BD

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