Diphenhydramine
Diphenhydramine is a **first-generation ethanolamine-derivative antihistamine** widely used in veterinary medicine. * **Primary Indications**: Management of allergic reactions (urticaria, angioedema, atopy), pruritus, and anaphylaxis. * **Secondary Indications**: Prevention of motion sickness, mild sedation, and as an antiemetic. **Clinical Pearls**: * Because it readily crosses the blood-brain barrier, it causes more pronounced CNS depression (sedation) compared to second-generation antihistamines (e.g., cetirizine, loratadine). * In cats, histamine is not considered a primary mediator of emesis. Therefore, NK-1 antagonists (like maropitant) or M1-cholinergic antagonists are generally preferred over diphenhydramine for treating feline motion sickness or vomiting. * It is sometimes used as an adjunctive treatment for aseptic laminitis in cattle and feline pancreatitis.
Mechanism: Diphenhydramine exerts its effects through multiple pathways: * **H1-Receptor Antagonism**: Competitively binds to and blocks **H1 receptors** on effector cells โ prevents histamine-mediated capillary permeability, vasodilation, and smooth muscle spasms (bronchoconstriction). * **Central Effects**: Readily crosses the blood-brain barrier โ blocks central **H1 receptors** โ produces sedation and antiemetic effects. * **Anticholinergic Activity**: Non-selectively binds to **muscarinic receptors** โ decreases exocrine secretions (drying effect) and can cause urinary retention or tachycardia. * **Additional Effects**: Possesses mild antitussive properties.
Dosing by species
- As an antihistamine ยท 0.5 mg/kg ยท PO ยท q12h ยท Liquid formulation is distasteful
- As an antihistamine ยท 2-4 mg (total dose) ยท PO ยท q12-24h
- As an antihistamine ยท 2-4 mg/kg ยท PO ยท q8h
- For severe urticaria and angioedema ยท 2 mg/kg ยท IM ยท twice daily as needed ยท Used with steroids (prednisone 2 mg/kg IM twice daily) and epinephrine 1:10,000 (0.5-2 mL SC)
- For adjunctive treatment of pancreatitis ยท 2-4 mg/kg ยท PO ยท q8h
- Prevaccination ยท 2 mg/kg ยท PO, IM or IV ยท 10 minutes prior to vaccination
- Pretreatment before doxorubicin ยท 5 mg (total dose) ยท IM ยท Single dose
- For adjunctive therapy of anaphylaxis ยท 0.5-1 mg/kg ยท IM or IV ยท Single dose ยท Used with epinephrine and steroids
- For adjunctive therapy of aseptic laminitis ยท 55-110 mg/100 kg body weight (0.55-1.1 mg/kg) ยท IV or IM ยท Single dose ยท During the acute phase ยท Used with corticosteroids
Routes of administration
Contraindications
- Hypersensitivity to diphenhydramine or other antihistamines in its class
- Angle closure glaucoma
- Prostatic hypertrophy
- Pyloroduodenal or bladder neck obstruction
- COPD (if mucosal secretions are a problem)
- Hyperthyroidism (use with caution)
- Cardiovascular disease or hypertension (use with caution)
- Seizure disorders (use with caution)
- Known hypersensitivity to diphenhydramine
- Glaucoma (due to anticholinergic effects)
- Prostatic hypertrophy or urinary retention
- Gastrointestinal obstruction
- Use with caution in working dogs due to sedation
Adverse effects
- CNS depression (lethargy, somnolence)
- Anticholinergic effects (dry mouth, urinary retention)
- GI effects (diarrhea, vomiting, anorexia)
- Paradoxical excitement (especially in cats)
- Sedation/lethargy
- Dry mouth (xerostomia)
- Urinary retention
- Tachycardia
- Gastrointestinal disturbances (diarrhea, vomiting, anorexia)
Drug interactions
- Anticholinergic drugs (including tricyclic antidepressants) ยท May potentiate anticholinergic effects
- CNS depressant drugs ยท Increased sedation can occur
- CNS Depressants (e.g., opioids, benzodiazepines, barbiturates) ยท Additive sedation and central nervous system depression ยท moderate
- Anticholinergic drugs ยท Additive anticholinergic effects (dry mouth, tachycardia, urinary retention) ยท moderate
- Monoamine Oxidase Inhibitors (MAOIs) ยท May prolong and intensify the anticholinergic effects of antihistamines ยท major
- CNS Depressants (e.g., Diazepam, Phenobarbital, Gabapentin) ยท Additive CNS depression and sedation ยท moderate
- Anticholinergic drugs (e.g., Atropine, Glycopyrrolate) ยท Additive anticholinergic effects (tachycardia, dry mouth, ileus) ยท moderate
- Tricyclic Antidepressants (e.g., Amitriptyline) ยท Increased risk of anticholinergic toxicity and sedation ยท moderate
Monitoring
- Clinical efficacy (reduction in pruritus, allergic signs, or vomiting)
- Adverse effects (excessive sedation, anticholinergic signs)
- Resolution of allergic signs or pruritus
- Degree of sedation
- Heart rate (monitor for tachycardia)
- Urination frequency (monitor for retention)
Overdose
Overdosage can cause **CNS stimulation** (ranging from excitement to seizures) or **CNS depression** (lethargy to coma), severe anticholinergic effects, respiratory depression, and death. **Treatment**: * Empty the gut after oral ingestion using standard protocols. * Induce emesis if the patient is alert and CNS status is stable. * Administer a saline cathartic and/or activated charcoal after emesis or gastric lavage. * Provide symptomatic and supportive therapies. * **Seizure management**: Phenytoin (IV) is recommended in humans for seizures caused by antihistamine overdose; **barbiturates and diazepam should be avoided**.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.