Transcript Chapter 16 Cholinesterase Inhibitors

Chapter 70
Antihistamines
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Histamine



Endogenous compound
Found in specialized cells
Important role in:



Allergic reaction
Regulation of gastric acid secretion
Histamine use limited to diagnostic
procedures
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
2
Histamine

Distribution



Present in practically all tissues
Especially high in skin, lungs, and GI tract
Low content in plasma
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
3
Histamine

Synthesis/storage



Mast cells and basophils
Produced by neurons
Release


Allergic
Nonallergic
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
4
Fig. 70–1. Release of histamine by allergen-antibody interaction.
(IgE = immunoglobulin E.)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
5
Histamine Receptors

H1 receptor





Vasodilation
Increased capillary permeability
Bronchoconstriction
CNS effects
Other
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
6
H1 Receptors

Vasodilation



Increased capillary permeability


Not the cause of asthma attack
CNS effects


Edema
Bronchoconstriction


Skin of the face and upper body
Extensive: can cause hypotension
Role in cognition, memory, and sleep-waking
cycles
Other

Itching, pain, secretion of mucus
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
7
H2 Receptors



Secretion of gastric acid
Act directly on parietal cells to promote acid
release
Dominant role in acid release
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
8
Histamine
Antagonists/Antihistamines


Act primarily on H1 and H2 receptors
Used primarily for two pathologic states
1. Allergic disorders
2. Peptic ulcer disease
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
9
Allergic Responses

Mediated by histamine and other compounds



Prostaglandins
Leukotrienes
Tryptase
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
10
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
11
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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
12
Two Types of Antihistamines

H1 antagonists



Produce selective blockade of H1 receptors
Used for treatment of mild allergic disorders
H2 antagonists



Produce selective blockade of H2 receptors
Used for treatment of gastric and duodenal ulcers
Not used for treatment of allergies
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
13
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 bind to muscarinic receptors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
14
H1 Antagonists

Pharmacologic effects


Peripheral effects
• Reduce localized flushing
• Reduce itching and pain
Effects on the CNS
• Therapeutic dose: CNS depression

Second-generation negligible CNS depression

CNS stimulation
Convulsions
Very young children especially sensitive to CNS stimulation
• Overdose


Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
15
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
16
H1 Antagonists

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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
17
H1 Antagonists

Adverse effects



Severe respiratory depression
Severe local tissue injury
Cardiac dysrhythmias
• Rare
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
18
H1 Antagonists

Drug interactions



CNS depressants
Use of pregnancy and lactation
Acute toxicity



Large margin of safety
Widespread availability of drugs
CNS and anticholinergic reactions
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
19
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
20
H1 Antagonists: First Generation
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
21
H1 Antagonists: Second Generation

Second generation (nonsedating)





Fexofenadine (Allegra)
Cetirizine (Zyrtec)
Levocetirizine (Xyza)
Loratadine (Claritin, Tavist ND, Alavert)
Desloratadine (Clarinex)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
22