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H1-receptor antagonists: safety issues.

F Estelle1, R Simons

  • 1Department of Pediatrics and Child Health, University of Manitoba, Canada.

Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology
|December 3, 1999
PubMed
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First-generation H1-antagonists cause central nervous system (CNS) effects, while newer options offer improved safety. However, no H1-antagonist is completely free from potential adverse effects.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Medicinal Chemistry

Background:

  • Histamine acts as a crucial neurotransmitter in the central nervous system (CNS).
  • First-generation H1-receptor antagonists (e.g., chlorpheniramine) readily cross the blood-brain barrier, leading to CNS adverse effects like somnolence.
  • Second-generation H1-antagonists demonstrate improved safety profiles due to reduced CNS penetration.

Purpose of the Study:

  • To compare the central nervous system (CNS) penetration and adverse effect profiles of first-generation versus second-generation H1-receptor antagonists.
  • To review the safety concerns associated with specific H1-antagonists, including cardiac effects.

Main Methods:

  • Review of existing pharmacological data and clinical studies on H1-receptor antagonists.

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  • Comparative analysis of CNS penetration, somnolence, and other CNS-related adverse effects.
  • Examination of specific drug safety data, including QTc interval prolongation and cardiac dysrhythmias.

    • Main Results:

    • First-generation H1-antagonists cause significant CNS adverse effects, including somnolence.
    • Second-generation H1-antagonists (e.g., cetirizine, fexofenadine, loratadine) exhibit minimal CNS penetration and fewer adverse effects at recommended doses.
    • Astemizole and terfenadine were associated with QTc prolongation and cardiac risks, leading to their withdrawal from the market.

    Conclusions:

    • Second-generation H1-antagonists represent a significant therapeutic advancement over older agents due to their improved CNS safety.
    • Despite advancements, a completely safe H1-antagonist without any potential adverse effects under all circumstances is not yet available.
    • Careful consideration of drug safety profiles, including potential cardiac risks, remains essential when selecting H1-antagonists.