Chapter 56: Antihisamines Flashcards
Histamine
Endogenous, locally acting compound
Found in specialized cells
Important role in:
Allergic reaction
Regulation of gastric acid secretion
Histamine use limited to diagnostic procedures
Histamine distribution
Present in practically all tissues
Especially high in skin, lungs, and gastrointestinal (GI) tract
Low content in plasma
Histamine synthesis/storage
Mast cells and basophils
Produced by neurons in posterior hypothalamus with atonal projections to the frontal and temporal cortices and other areas of the brain
Histamine release
Allergic: Allergic release of histamine requires prior exposure to the allergen; an allergic reaction cannot occur during initial allergen exposure.
Nonallergic: Several agents (certain drugs, radiocontrast media, plasma expanders) can act directly on mast cells to trigger histamine release. With these agents, no prior sensitization is needed. Cell injury can also cause direct release.
H1 Receptors activation
Vasodilation
Skin of the face and upper body
Extensive vasodilation 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
H2 Receptors activation
Secretion of gastric acid
Act directly on parietal cells to promote acid release
Dominant role in acid release
Role of Histamine in Allergic Response: mild allergy
Rhinitis, itching, localized edema are caused largely by histamine, acting at H1 receptors
Role of Histamine in Allergic Response: severe anaphylactic reaction
Anaphylactic shock: Bronchoconstriction, hypotension, and edema of the glottis
Histamine plays a minor role
Leukotrienes: Principal mediators
Antihistamines are little help as treatment
Epinephrine is the drug of choice
Two Types of Antihistamines: H1 Antagonists and H2 Antagonists
The principal use of H1 blockers is the treatment of mild allergic disorders
Produce selective blockade of H1 receptors
Used for treatment of mild allergic disorders
The principal use of H2 blockers is the treatment of gastric and duodenal ulcers
Produce selective blockade of H2 receptors
Used for treatment of gastric and duodenal ulcers
Not used for treatment of allergies
H1 Antagonists: 2 groups
First-generation H1 antagonists (highly sedating)
Second-generation H1 antagonists
H1 antagonists MOA
Block the actions of histamine at H1 receptors
Do not block H2 receptors
Some bind to muscarinic receptors
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
Overdose
CNS stimulation
Convulsions
Very young children especially sensitive to CNS stimulation
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
H1 antagonists ADR
Sedation
Less with second and third generation
Nonsedative CNS effects
Dizziness, fatigue, coordination problems, confusion
GI effects
Can cause nausea, vomiting, loss of appetite, constipation (give with food)
Anticholinergic effects
Weak atropine-like effects
Severe respiratory depression
Severe local tissue injury
1st generation H1 antagonist
OTC
Benadryl, Chlor-trimeton, phenergan, vistaril
H1 antagonists: second generations
OTC
Cetirizine -Zyrtec, Xyzal, Fexofenadine -Allegra, Loratadine -Claritin, Clarinex
H1 antagonists drug interactions
CNS depressants
H1 antagonists use during pregnancy and lactation
Unknown with pregnancy –only use when benefit outweigh risks, avoid late in 3rd trimester
Can be excreted in milk, present a risk to the infant
Acute toxicity of H1 antagonists
Large margin of safety
Widespread availability of drugs
CNS and anticholinergic reactions: Dilated pupils, flushed face, hyperpyrexia, tachycardia, dry mouth, urinary retention
Children: CNS excitation
Extreme cases: Coma, cardiovascular collapse, death
H1 antagonist acute toxicity tx
No specific antidote to antihistamine poisoning
Treatment directed at drug removal and managing symptoms
Activated charcoal
Cathartic
Convulsions: IV benzodiazepines (lorazepam, midazolam)
Hyperthermia: Ice packs or sponge baths
H1 antagonists contraindications
Third trimester of pregnancy
Nursing mothers
Newborn infants
H1 antagonists caution
Young children
Older adults
Patients whose conditions may be aggravated by muscarinic blockade
H1 antagonists 2nd gen
Produce much less sedation than first-generation agents
Cross the blood-brain barrier poorly
Have a low affinity for H1 receptors of the CNS
Largely devoid of anticholinergic actions
Fexofenadine [Allegra, Allegra Allergy, Allegra ODT]
Uses: Oral therapy of seasonal allergic rhinitis and for chronic idiopathic urticaria
Of second-generation antihistamines, offers best combination of efficacy and safety
Use with caution in patients with renal impairment
Do not take with citrus fruit juice
Decreases absorption of medication
Cetirizine [Zyrtec]
Uses: Allergic rhinitis and chronic idiopathic urticaria
Food delays absorption
More sedating than other second-generation antihistamines but less sedating than first-generation drugs
Levocetirizine [Xyzal]
Uses: Allergic rhinitis and chronic idiopathic urticaria
More sedating than other second-generation antihistamines but less sedating than first-generation agents
Most common side effects: Drowsiness, fatigue, muscle weakness, dry mouth
Avoid alcohol and other CNS depressants
Loratadine [Claritin]
Use: Seasonal allergic rhinitis
Generally well tolerated
Food delays absorption
Use with caution in patients with significant hepatic and renal impairment
Desloratadine [Clarinex]
Uses: Seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria
