ANTI-INFLAMMATORY,
ANTIALLERGIC DRUGS
ANTIHISTAMINES
Histamine
◦
Distribution
◦
Present in practically all tissues
◦
Especially high in skin, lungs, and GI tract
◦
Low content in plasma
Histamine Receptors
◦
H
1
receptor
◦
Vasodilation
◦
Increased capillary permeability
◦
Bronchoconstriction
◦
CNS effects
◦
Other
H
1
Receptors
◦
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
H
2
Receptors
◦
Secretion of gastric acid
◦
Act directly on parietal cells to promote acid release
◦
Dominant role in acid release
Histamine
Antagonists/Antihistamines
◦
Act primarily on H
1
and H
2
receptors
◦
Used primarily for two pathologic states
1.
Allergic disorders
2.
Peptic ulcer disease
Allergic Responses
◦
Mediated by histamine and other compounds
◦
Prostaglandins
◦
Leukotrienes
◦
Tryptase
Mild Allergic Responses
◦
Caused largely by histamine acting at H
1
receptors
◦
Rhinitis, itching, localized edema
◦
Hay fever, mild transfusion reaction, acute urticaria
◦
Usually responsive to antihistamine therapy
Two Types of Antihistamines
◦
H
1
antagonists
◦
Produce selective blockade of H
1
receptors
◦
Used for treatment of mild allergic disorders
◦
H
2
antagonists
◦
Produce selective blockade of H
2
receptors
◦
Used for treatment of gastric and duodenal ulcers
◦
Not used for treatment of allergies
H
1
Antagonists
◦
H
1
antagonists are divided into two major groups:
◦
First-generation H
1
antagonists (highly sedating)
◦
Second-generation H
1
antagonists
◦
Mechanism of action
◦
Block the actions of histamine at H
1
receptors
◦
Do not block H
2
receptors
◦
Some bind to muscarinic receptors
H
1
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
◦
Overdose
◦
CNS stimulation
◦
Convulsions
◦
Very young children especially sensitive to CNS stimulation
H
1
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 H
1
blockade
H
1
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
H
1
Antagonists
◦
Adverse effects
◦
Severe respiratory depression
◦
Severe local tissue injury
◦
Cardiac dysrhythmias
◦
Rare
