Chapter 70 Antihistamines 1

Histamine Endogenous compound Found in specialized cells Important role in: Allergic reaction Regulation of gastric acid secretion Histamine use limited to diagnostic procedures 2

Histamine Distribution Present in practically all tissues Especially high in skin, lungs, and GI tract Low content in plasma 3

Histamine Synthesis/storage Release Mast cells and basophils Produced by neurons Release Allergic Nonallergic 4

Fig. 70–1. Release of histamine by allergen-antibody interaction. (IgE = immunoglobulin E.) 5

Histamine Receptors H1 receptor stimulated: Vasodilation Increased capillary permeability Bronchoconstriction CNS effects Other 6

H1 Receptors Vasodilation Increased capillary permeability 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 7

Allergic Responses Mediated by histamine and other compounds (which are more important in anaphylaxis and in pathophysiology of asthma) Prostaglandins Leukotrienes Tryptase 8

Mild Allergic Responses Caused largely by histamine acting at H1 receptors Rhinitis, itching, localized edema Hay fever, mild transfusion reaction, acute urticaria Usually responsive to antihistamine therapy 9

Severe Allergic Responses 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) 10

H1 Antagonists H1 antagonists are divided into two major groups: First-generation H1 antagonists (highly sedating) Second-generation H1 antagonists Mechanism of action Block the actions of histamine at H1 receptors Do not block H2 receptors Some block to muscarinic receptors 11

H1 Antagonists (first generation- which cross blood-brain barrier) 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 to CNS stimulation 12

H1 Antagonists Therapeutic uses Mild allergy Severe allergy Adjunct only, benefits may be limited Motion sickness Promethazine, dimenhydrinate Insomnia Common cold May decrease rhinorrhea through anticholinergic properties, not H1 blockade 13

H1 Antagonists (first-generation) Adverse effects Sedation Less with second and third generation Nonsedative CNS effects Dizziness, fatigue, coordination problems, confusion Gastrointestinal effects Can cause nausea, vomiting, loss of appetite, constipation (give with food) Anticholinergic effects Weak atropine-like effects 14

H1 Antagonists Adverse effects Severe respiratory depression Severe local tissue injury Cardiac dysrhythmias Rare 15

H1 Antagonists (first-generation) Drug interactions CNS depressants Use of pregnancy and lactation Acute toxicity Large margin of safety Widespread availability of drugs CNS and anticholinergic reactions Hot, dry, red skin and delirium 16

High-Risk Patients Antihistamines contraindicated During third trimester of pregnancy Nursing mothers Newborn infants Use antihistamines with caution in: Young children Older adults Patients whose conditions may be aggravated by muscarinic blockade 17

H1 antagonists (first generation)- names Diphenhydramine (Benadryl) Hydroxyzine (Vistaril) Promethazine (Phenergen) Chlorphiramine Clemastine (Tavist Allergy)

H1 Antagonists: Second Generation Second generation (nonsedating) Fexofenadine (Allegra) Cetirizine (Zyrtec) Levocetirizine (Xyza) Loratadine (Claritin, Tavist ND, Alavert) Desloratadine (Clarinex) 19