Antihistamines “H1 antihistamines” Dr. Ahmed Goda Associate Professor Department of Pharmacology and Toxicology Faculty of Pharmacy Tanta University Terminology Autacoids Locally acting (autocrine & paracrine) Half life: few sec.~few min. 5-HT Histamine - Antihistaminics Eicosanoids 20-carbons fatty acid derivatives (e.g., AA) Prostaglandins Leukotrienes Epoxides Urticaria Conjunctivitis Angioedema First Generation Second Generation Third Generation Diphenhydramine Loratidine Desloratidine Dimenhydrinate Cetrizine Levocitrizine Meclizine Fexofenadine Doxylamine Pheniramine Chlorpheniramine Mepyramine Cyproheptadine Promethazine ➢ Allergic conditions (disease-induced “e.g., urticaria, rhinitis, conjunctivitis”, drug-induced, food allergy, insect stings, …etc). ➢ Anaphylaxis (??) Indic. ➢ Motion sickness / nausea of pregnancy (esp., diphenhydramine, dimenhydrinate, meclizine, doxylamine) ➢ Sedation (esp., diphenhydramine, doxylamine) Side Effects First Generation Second Generation Third Generation Diphenhydramine Loratidine Desloratidine Dimenhydrinate Cetrizine Levocitrizine Meclizine Fexofenadine Doxylamine Pheniramine Chlorpheniramine Mepyramine Cyproheptadine Promethazine ➢ Competitive antagonists at H1 receptors. M.O.A ➢ Variable binding to other receptors (cholinergic, adrenergic, or serotonin) SE First Generation Second Generation Third Generation Diphenhydramine Loratidine Desloratidine Dimenhydrinate Cetrizine Levocitrizine Meclizine Fexofenadine Doxylamine Pheniramine Chlorpheniramine Mepyramine Cyproheptadine Promethazine ➢ Antihistaminic: drowsiness, ↓ psychomotor activity (esp. 1st gen.) ➢ Anticholinergic: dry mouth, urine retention, constipation, blurred vision, SE tachycardia (esp. 1st gen.) ➢ Antiadrenergic: hypotension, reflex tachycardia (esp. promethazine) ➢ Antiserotonergic: ↑ appetite (esp. Cyproheptadine) First Generation Second Generation Third Generation Diphenhydramine Loratidine Desloratidine Dimenhydrinate Cetrizine Levocitrizine Meclizine Fexofenadine Doxylamine Pheniramine Chlorpheniramine Mepyramine Cyproheptadine Promethazine A Almost complete st D widely distributed (1 gen. cross BBB, t1/2:4-6 hrs) PK other generations longer t1/2 (loratadine: 24hrs, desloratidine: 27 hrs) M Hepatic (except fexofenadine: largely unchanged) E Renal (except fexofenadine: fecal) First Generation Second Generation Third Generation Diphenhydramine Loratidine Desloratidine Dimenhydrinate Cetrizine Levocitrizine Meclizine Fexofenadine Doxylamine Pheniramine Chlorpheniramine Mepyramine Cyproheptadine Promethazine CNS depressants potentiation of CNS depression DI MAOI potentiation of anticholinergic activity.