Download Antihistamines

Antihistamines
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
*
Endogenous compound
Found in specialized cells (mast cells)
*
Important role in:
*
• Allergic reaction (H1)
• Regulation of gastric acid secretion (H2)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
2
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.
3
Synthesis/storage
• Mast cells (skin & other soft tissues)
• Basophils (blood)
Stored in
secretory
granules
• In CNS, histamine is produced by neurons
Release
• Allergic
• Nonallergic
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
4
Release of histamine by
allergen-antibody interaction
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
5
 H1 receptor
• Vasodilation
• Increased capillary permeability
• Bronchoconstriction
• CNS effects
• Other
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
6
 Vasodilation
• Skin of the face and upper body
• Extensive – can cause hypotension
 Increased
• Edema
capillary permeability
 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.
7
 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.
8


Act primarily on H1 and H2 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.
9
 Mediated
by histamine & other
compounds
• Prostaglandins
• Leukotrienes
• Tryptase
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
10




Caused largely by histamine acting at H1
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.
11
 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.
12
 Antihistamines, histamine
antagonists, and
histamine blockers are used interchangeably.
 H1 antagonists have similar antihistamine
actions but differ significantly in side effects.
 No individual prototype selected.
 H1 antagonists are divided into two major
groups:
• First-generation H1 antagonists (highly
sedating)
• Second-generation H1 antagonists
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
13
 Mechanism of action
• Block the actions of histamine at H1 receptors
• Do not block H2 receptors
• Some bind to muscarinic receptors
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
14
 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.
15
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
16
 Therapeutic uses
• Mild allergy
• Motion sickness
 Promethazine, dimenhydrinate
• Insomnia
• Common cold
 Anticholinergic properties, not H1 blockade
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
17
 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.
18
 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.
19
 First generation (sedating)
• Diphenhydramine (Benadryl) *
• Hydroxyzine (Atarax)
• Promethazine (Phenergan)*
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
20
 Second generation (nonsedating)
• Fexofenadine (Allegra)
• Cetirizine (Zyrtec)
• Loratadine (Claritin)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
21
 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
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
22
W2
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
23