Is diphenhydramine (Benadryl) an anticholinergic medication?

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From the Guidelines

Diphenhydramine, also known as Benadryl, is indeed an anticholinergic medication with significant anticholinergic properties, which can lead to side effects such as dry mouth, blurred vision, urinary retention, and constipation, as seen in the study published in Gastroenterology in 2024 1. The anticholinergic effects of diphenhydramine occur because it blocks muscarinic acetylcholine receptors in the body, contributing to its sedating effects, making it commonly used for allergic reactions, as a sleep aid, and for motion sickness. Some key points to consider when using diphenhydramine include:

  • Typical doses of 25-50mg every 4-6 hours, not exceeding 300mg in 24 hours for adults
  • Anticholinergic properties can cause cognitive impairment, especially in older adults
  • Should be used with caution in the elderly, those with glaucoma, prostatic hypertrophy, or certain heart conditions, as noted in the study published in Mayo Clinic Proceedings in 2021 1
  • Alternative medications, such as nonsedating H1 antihistamines, may be preferred to minimize anticholinergic effects, as suggested in the study published in the Journal of Allergy and Clinical Immunology in 2019 1.

From the Research

Diphenhydramine and Benadryl

  • Diphenhydramine is commonly known by the brand name Benadryl, which is an antihistamine medication.
  • It is used to treat various conditions such as allergies, insomnia, and itching [ 2, 3 ].

Anticholinergic Effects

  • Diphenhydramine has anticholinergic properties, which can lead to side effects such as sedation, dry mouth, and urinary retention [ 4, 5 ].
  • The anticholinergic effects of diphenhydramine can be particularly problematic in certain populations, such as older adults and children with chronic illnesses [ 2, 4 ].

Comparison with Other Antihistamines

  • Diphenhydramine is a first-generation antihistamine, which can have more sedating effects compared to newer, second-generation antihistamines [ 3, 5 ].
  • Second-generation antihistamines, such as loratadine and fexofenadine, may be preferred over diphenhydramine due to their lower risk of sedation and anticholinergic side effects [ 3, 5 ].

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diphenhydramine: Time to Move on?

The journal of allergy and clinical immunology. In practice, 2022

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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