Diphenhydramine
Diphenhydramine
Generic Name
Diphenhydramine
Brand Names
Benadryl) is a first‑generation, non‑selective antihistamine that also exhibits potent anticholinergic activity. It remains one of the most widely used over‑the‑counter agents for allergic symptoms and short‑term insomnia.
Mechanism
- H1 receptor antagonism: Reverses the effects of histamine by competitively inhibiting peripheral and central histamine H1 receptors.
- Anticholinergic blockade: Blocks muscarinic acetylcholine receptors (M1–M5), leading to drowsiness, dry mouth, urinary retention, and decreased GI motility.
- Blood–brain barrier penetration: High lipophilicity allows central nervous system access, producing pronounced sedation and, at higher doses, antimuscarinic delirium.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Rapid oral uptake; peak plasma levels in 30–90 min. |
| Bioavailability | ~30–50 % (first‑pass hepatic metabolism). |
| Distribution | Volume of distribution ≈ 5 L/kg; ~85 % protein binding. |
| Metabolism | Hepatic N‑dealkylation → 2‑dimethylamino‑phenyl‑ethanol; conjugated via glucuronidation. |
| Elimination half‑life | 3–8 hrs (shorter in children, longer in elderly). |
| Excretion | Renal (≈25–35 % unchanged) and biliary. |
Note: Renal or hepatic insufficiency may prolong elimination; dosing adjustments are advised.
Indications
- Allergic rhinitis (nasal congestion, sneezing, itching).
- Urticaria & angioedema (non‑immediate, non‑anaphylactic).
- Skin pruritus (eczema, insect bites).
- Post‑operative nausea and vomiting prophylaxis (at low dose).
- Short‑term insomnia (dose ≤ 25 mg every 4–6 h).
Contraindications
- Absolute contraindications: Glaucoma, prostatic hypertrophy, acute urinary retention, severe hepatic or renal failure (dose‑adjusted).
- Warnings:
- *Anticholinergic toxicity*: high doses can cause delirium, visual hallucinations, confusion.
- *CNS depression*: should not be combined with alcohol, benzodiazepines, or opioids.
- *Pregnancy*: Category B; limited data—use only if benefits outweigh risks.
- *Lactation*: excreted in breast milk; advise caution.
Dosing
| Population | Adult | Pediatric (4 kg–12 yr) | <4 kg |
| Typical dose | 25 mg orally every 4–6 h (max 300 mg/24 h). | 0.5–1 mg/kg (max 25 mg) PO/SL or IM every 6 h. | 0.5 mg/kg PO/SL every 6 h (max 15 mg). |
| Route | Oral (tablet/chewable), intramuscular, rectal. | Oral or IM (if oral not tolerated). | Intramuscular or rectal if oral/IV not feasible. |
| Insomnia | 25 mg 30 min before bedtime; may increase to 50 mg if needed. | Avoid; use with caution. | Not recommended. |
Adverse Effects
Common (≥ 5 %)
• Drowsiness, dizziness
• Dry mouth, blurred vision
• Urinary retention, constipation
• Transient tachycardia
Serious (≤ 1 %)
• Severe anticholinergic syndrome (confusion, delirium, seizures)
• Hypotension, arrhythmias (rare)
• Pulmonary aspiration (with sleep‑inducing doses)
• Idiosyncratic hypersensitivity (rare)
Monitoring
- Vitals: BP, HR, RR, O₂ saturation, especially when initiating therapy.
- CNS: Assessment for sedation, confusion, or delirium.
- Renal & hepatic panels: In chronic or high‑dose use (> 50 mg QID).
- Pediatric: Monitor for ataxia, excessive salivation, and signs of overdose.
Clinical Pearls
- Sedation vs. Anxiolysis: Because of its high central penetration, diphenhydramine’s antihistaminic effect can be exploited for mild short‑term insomnia, but this is not its primary indication—avoid long‑term use.
- First‑line in acute urticaria: While newer H1 blockers are preferred for chronic urticaria, diphenhydramine remains the first choice for rapidly controlling acute, moderate‑to‑severe itching due to its quick onset and high potency.
- Avoid in children <4 yr: The risk of CNS depression outweighs benefits; prefer second‑generation antihistamines.
- Drug interactions: Additive CNS depression with alcohol, opioids, benzodiazepines, and CNS‑depressant antihistamines (e.g., doxylamine). Concomitant SSRIs may increase anticholinergic burden.
- Reversal in toxicity: Atropine 0.5 mg IV may reverse severe anticholinergic signs; physostigmine is contraindicated due to potential for arrhythmia.
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• Diphenhydramine remains a cornerstone therapy for allergic and itching conditions, but its anticholinergic profile necessitates mindful dosing, particularly in vulnerable populations. Use it judiciously, monitor for adverse effects, and educate patients about the potential for drowsiness and impaired psychomotor performance.