1. Chapter 70
Antihistamines 1

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

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

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

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

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

7. 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

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

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

16. 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

17. 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

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

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