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First-Generation Antihistamine

Diphenhydramine | Benadryl

Clinical Overview

Diphenhydramine is a first-generation antihistamine with anticholinergic and sedative properties indicated for allergic reactions, motion sickness, insomnia, and various other conditions. It is one of the most widely used over-the-counter medications but requires careful consideration due to its significant anticholinergic effects, particularly in elderly patients.

Primary Clinical Applications

Diphenhydramine is indicated for allergic reactions, seasonal allergies, motion sickness, insomnia, cough suppression, and as an adjunct in treating extrapyramidal symptoms. It is available in multiple formulations including oral, topical, and injectable forms for various clinical situations.

Mechanism and Clinical Benefits

Diphenhydramine blocks histamine H1 receptors and has significant anticholinergic activity. It provides antihistaminic, sedative, antiemetic, antitussive, and local anesthetic effects. The sedating properties make it useful for sleep disorders but also contribute to its side effect profile.

Safety Considerations

While generally safe when used appropriately, diphenhydramine can cause significant anticholinergic toxicity, especially in elderly patients or with overdose. It interacts with numerous medications and can impair cognitive function and increase fall risk in susceptible populations.

Prescribing Information

Dosing & Administration

Allergic Reactions – Adults:

  • Oral: 25-50 mg every 4-6 hours
  • Maximum: 300 mg daily
  • IV/IM: 10-50 mg, maximum 400 mg daily

Insomnia – Adults:

  • Oral: 25-50 mg at bedtime

Motion Sickness – Adults:

  • Oral: 25-50 mg every 4-6 hours
  • Prevention: 30 minutes before travel

Pediatric (≥2 years):

  • Oral: 1.25 mg/kg every 4-6 hours
  • Maximum: 37.5 mg every 4-6 hours

Elderly:

  • Use lower doses due to increased sensitivity
  • Avoid if possible due to anticholinergic effects

Indications

  • Allergic reactions and seasonal allergies
  • Motion sickness
  • Insomnia (short-term)
  • Cough suppression
  • Extrapyramidal symptoms (adjunct)

Contraindications

  • Hypersensitivity to diphenhydramine
  • Newborns and premature infants
  • Nursing mothers (if high doses used)
  • Acute asthma attack
  • Narrow-angle glaucoma
  • Bladder neck obstruction

Warnings & Precautions

  • Anticholinergic toxicity: Especially in elderly patients
  • CNS depression: Impaired alertness and coordination
  • Respiratory depression: Risk in compromised patients
  • Paradoxical excitation: Particularly in children
  • Falls risk: Due to sedation and orthostatic hypotension
  • Cognitive impairment: Memory and attention effects

Drug Interactions

  • CNS depressants: Enhanced sedation
  • Anticholinergic drugs: Additive anticholinergic effects
  • MAOIs: Prolonged anticholinergic effects
  • Alcohol: Increased CNS depression

Adverse Reactions

Common:

  • Drowsiness, dizziness, dry mouth, blurred vision, constipation

Anticholinergic Effects:

  • Urinary retention, confusion, memory impairment

Serious:

  • Anticholinergic toxicity, respiratory depression, seizures

Special Populations

  • Elderly: Avoid due to high anticholinergic burden (Beers Criteria)
  • Pregnancy: Category B – generally considered safe
  • Pediatric: Risk of paradoxical excitation
  • Hepatic impairment: Use with caution, consider dose reduction
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.