====== First-Generation Antihistamines ======

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

See histamine physiology:
  * [[allergy:immunology:histamine_physiology|Histamine Physiology]]
  * [[allergy:immunology:type_i_hypersensitivity|Type I Hypersensitivity]]

Second-generation agents:
  * [[allergy:drug_classes:second_generation_h1|Second-Generation Antihistamines]]

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===== Mechanism of Action =====

  * Competitive antagonists at H1 receptors
  * Block histamine-mediated:
      - Vasodilation
      - Increased vascular permeability
      - Pruritus
      - Bronchoconstriction

Additional properties:

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

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===== Pharmacologic Characteristics =====

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

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===== Drugs =====

  * [[allergy:drugs:diphenhydramine|Diphenhydramine]]
  * [[allergy:drugs:chlorpheniramine|Chlorpheniramine]]
  * [[allergy:drugs:brompheniramine|Brompheniramine]]
  * [[allergy:drugs:clemastine|Clemastine]]
  * [[allergy:drugs:hydroxyzine|Hydroxyzine]]
  * [[allergy:drugs:promethazine|Promethazine]]
  * [[allergy:drugs:doxylamine|Doxylamine]]
  * [[allergy:drugs:meclizine|Meclizine]]
  * [[allergy:drugs:dimenhydrinate|Dimenhydrinate]]
  * [[allergy:drugs:cyproheptadine|Cyproheptadine]]

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===== Clinical Uses =====

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

Primary disease links:

  * [[allergy:clinical:allergic_rhinitis|Allergic Rhinitis]]
  * [[allergy:clinical:anaphylaxis|Anaphylaxis]]

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===== Adverse Effects =====

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

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===== Contraindications & Caution =====

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

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===== High-Yield Comparison =====

First-Generation:
  * Sedating
  * Anticholinergic
  * CNS penetration
  * Shorter acting

Second-Generation:
  * Minimal sedation
  * More selective
  * Longer acting
  * Fewer anticholinergic effects