First-Generation Antihistamines

First-generation antihistamines are H1 receptor antagonists that cross the blood-brain barrier and produce central sedation.

See histamine physiology:

• Histamine Physiology
• Type I Hypersensitivity

Second-generation agents:

• Second-Generation Antihistamines

• Competitive antagonists at H1 receptors
• Block histamine-mediated:
  1. Vasodilation
  2. Increased vascular permeability
  3. Pruritus
  4. Bronchoconstriction

Additional properties:

• Cross blood-brain barrier
• Anticholinergic (muscarinic blockade)
• Anti-alpha adrenergic effects (some agents)
• Sodium channel blockade (some agents)

• Lipophilic
• Sedating
• Shorter half-life
• Multiple receptor activity (non-selective)

• Diphenhydramine
• Chlorpheniramine
• Brompheniramine
• Clemastine
• Hydroxyzine
• Promethazine
• Doxylamine
• Meclizine
• Dimenhydrinate
• Cyproheptadine

• Acute allergic reactions
• Urticaria
• Motion sickness
• Insomnia (sedative effect)
• Nausea and vomiting
• Anxiety (hydroxyzine)
• Anaphylaxis adjunct therapy

Primary disease links:

• Allergic Rhinitis
• Anaphylaxis

Sedation:

• Drowsiness
• Impaired cognition
• Delirium (elderly risk)

Anticholinergic:

• Dry mouth
• Urinary retention
• Constipation
• Blurred vision
• Acute angle-closure glaucoma risk

Other:

• QT prolongation (some agents)
• Paradoxical excitation in children

• Elderly (Beers Criteria)
• BPH
• Narrow-angle glaucoma
• Concurrent CNS depressants

First-Generation:

• Sedating
• Anticholinergic
• CNS penetration
• Shorter acting

Second-Generation:

• Minimal sedation
• More selective
• Longer acting
• Fewer anticholinergic effects