Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Antihistamines

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 * Endogenous compound * Found in specialized cells (mast cells) * Important role in: Allergic reaction (H 1 ) Regulation of gastric acid secretion (H 2 )

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Distribution Present in practically all tissues Especially high - skin, lungs, and GI tract Low content in plasma

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 Synthesis/storage Mast cells (skin & other soft tissues) Basophils (blood) In CNS, histamine is produced by neurons Release Allergic Nonallergic Stored in secretory granules

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.5 Release of histamine by allergen-antibody interaction

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.6  H 1 receptor Vasodilation Increased capillary permeability Bronchoconstriction CNS effects Other

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.7  Vasodilation Skin of the face and upper body Extensive – can cause hypotension  Increased capillary permeability Edema  Bronchoconstriction Not the cause of asthma attack  CNS effects Role in cognition, memory, and sleep/waking cycles  Other Itching, pain, secretion of mucus

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.8  Secretion of gastric acid  Act directly on parietal cells to promote acid release  Dominant role in acid release

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.9  Act primarily on H 1 and H 2 receptors  Used primarily for two pathologic states Allergic disorders Peptic ulcer disease

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.10  Mediated by histamine & other compounds Prostaglandins Leukotrienes Tryptase

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.11  Caused largely by histamine acting at H 1 receptors  Rhinitis, itching, localized edema  Hay fever, mild transfusion reactions, acute urticaria  Usually responsive to antihistamine therapy

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.12  Anaphylaxis Anaphylactic shock  Bronchoconstriction, hypotension, edema of the glottis  Histamine plays a minor role  Leukotrienes are the principal mediators  Antihistamines are of little use in treatment  Epinephrine is the drug of choice for treatment (see Chapter 17)

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.13  Antihistamines, histamine antagonists, and histamine blockers are used interchangeably.  H 1 antagonists have similar antihistamine actions but differ significantly in side effects.  No individual prototype selected.  H 1 antagonists are divided into two major groups: First-generation H 1 antagonists (highly sedating) Second-generation H 1 antagonists

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.14  Mechanism of action Block the actions of histamine at H 1 receptors Do not block H 2 receptors Some bind to muscarinic receptors

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.15  Pharmacologic effects Peripheral effects  Reduce localized flushing  Reduce itching and pain Effects on the CNS  Therapeutic dose – CNS depression  Second-generation negligible CNS depression  Overdose  CNS stimulation  Convulsions  Very young children especially sensitive

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.16

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.17  Therapeutic uses Mild allergy Motion sickness  Promethazine, dimenhydrinate Insomnia Common cold  Anticholinergic properties, not H 1 blockade

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.18  Adverse effects Sedation Nonsedative CNS effects  Dizziness, fatigue, coordination problems Gastrointestinal effects  Can cause nausea, vomiting, loss of appetite, constipation Anticholinergic effects  Weak atropine-like effects Cardiac dysrhythmias  Rare

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.19  Drug interactions CNS depressants  Acute toxicity Large margin of safety Widespread availability of drugs CNS and anticholinergic reactions

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.20  First generation (sedating) Diphenhydramine (Benadryl) * Hydroxyzine (Atarax) Promethazine (Phenergan)*

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.21  Second generation (nonsedating) Fexofenadine (Allegra) Cetirizine (Zyrtec) Loratadine (Claritin)

Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.22  Antihistamines contraindicated During third trimester of pregnancy Nursing mothers Newborn infants  Use antihistamines with caution in: Young children The elderly Patients whose conditions may be aggravated by muscarinic blockade

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