Usage
Diphenhydramine, an antihistamine with anticholinergic and sedative properties, is prescribed for the symptomatic relief of allergic reactions (rhinitis, conjunctivitis, urticaria, angioedema), motion sickness, insomnia, and mild Parkinsonian symptoms. Citric acid is included in some formulations as a buffering agent. Diphenhydramine is categorized as an H1-receptor antagonist, an antihistamine.
Diphenhydramine competes with histamine for H1-receptor sites on effector cells, thus reducing the effects of histamine. It also possesses anticholinergic properties, leading to drying effects. Its sedative properties are attributed to its effect on the central nervous system.
Alternate Names
Diphenhydramine Hydrochloride.
Brand Names: Benadryl, Sominex, Unisom SleepGels (and many others).
How It Works
Pharmacodynamics: Diphenhydramine acts as an inverse agonist at the H1 histamine receptor, blocking the actions of histamine. Its anticholinergic effects result from competitive antagonism at muscarinic receptors. The sedative effects are likely due to its antagonism of histamine H1 receptors in the brain and its anticholinergic properties.
Pharmacokinetics: Diphenhydramine is rapidly absorbed after oral administration, reaching peak plasma concentrations in 1-4 hours. It is extensively metabolized in the liver, primarily by CYP2D6, to inactive metabolites. Elimination occurs primarily via renal excretion.
Mode of Action: At the cellular level, diphenhydramine competes with histamine for binding at H1 receptors. This prevents histamine from binding and initiating its effects, such as vasodilation, increased capillary permeability, and smooth muscle contraction. Its anticholinergic effects arise from blocking acetylcholine at muscarinic receptors, leading to reduced glandular secretions and smooth muscle relaxation.
Receptor Binding/Enzyme Inhibition: H1 receptor inverse agonist, Muscarinic receptor antagonist. May inhibit CYP2D6.
Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
Oral: 25-50 mg every 4-6 hours as needed. Maximum daily dose: 300 mg.
IM/IV: 10-50 mg (up to 100 mg if necessary), not to exceed 25 mg/minute. Maximum daily dose: 400 mg.
Children:
Oral (over 20 lbs / 9 kg): 12.5-25 mg every 4-6 hours. Maximum daily dose: 300 mg or 5mg/kg/24 hours.
Alternative weight-based dosing: 5 mg/kg/24 hours, divided into 4 doses. Do not exceed 300 mg/day.
Children 2-6 years: 6.25 mg every 4-6 hours as needed, maximum 37.5 mg/day.
Children 6-12 years: 12.5-25 mg every 4-6 hours as needed, maximum 150 mg/day.
Special Cases:
- Elderly Patients: Start with lower doses due to increased sensitivity to side effects (drowsiness, dizziness, confusion).
- Patients with Renal Impairment: Dose adjustment may be necessary depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Use with caution as diphenhydramine is metabolized in the liver. Dose adjustment may be necessary.
- Patients with Comorbid Conditions: Caution in patients with glaucoma, prostatic hypertrophy, bladder neck obstruction, peptic ulcer disease.
Clinical Use Cases
Diphenhydramine is not typically used in the clinical settings mentioned (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations). Other medications are generally preferred in these scenarios.
Dosage Adjustments
Dose modifications are based on renal/hepatic function, age, and concomitant medications.
Side Effects
Common Side Effects
Drowsiness, dizziness, dry mouth, blurred vision, constipation, urinary retention, nausea, and headache.
Rare but Serious Side Effects
Allergic reactions (anaphylaxis, angioedema), confusion, hallucinations, seizures, palpitations, tachycardia, hypotension, QT prolongation.
Long-Term Effects
Chronic use can lead to tolerance and dependence.
Adverse Drug Reactions (ADR)
Severe allergic reactions, cardiac arrhythmias, and seizures.
Contraindications
Hypersensitivity to diphenhydramine, neonates and premature infants, breastfeeding mothers, narrow-angle glaucoma, urinary retention, severe liver disease.
Drug Interactions
Alcohol, CNS depressants (e.g., benzodiazepines, opioids), MAOIs, anticholinergics (e.g., atropine).
Pregnancy and Breastfeeding
Pregnancy Category B. Use with caution during pregnancy only if clearly needed. Contraindicated in breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: H1 receptor inverse agonist, anticholinergic, sedative.
- Side Effects: Drowsiness, dry mouth, blurred vision, constipation, dizziness. Serious: allergic reactions, seizures, cardiac arrhythmias.
- Contraindications: Hypersensitivity, neonates/premature infants, breastfeeding, narrow-angle glaucoma, urinary retention.
- Drug Interactions: Alcohol, CNS depressants, MAOIs, anticholinergics.
- Pregnancy & Breastfeeding: Category B; contraindicated in breastfeeding.
- Dosage: Adults: 25-50 mg every 4-6 hours; Children: 12.5-25 mg every 4-6 hours (over 20 lbs).
- Monitoring Parameters: Heart rate, blood pressure, respiratory rate, mental status.
Popular Combinations
Diphenhydramine is often combined with other medications in over-the-counter products for cold and allergy symptoms (e.g., with analgesics like acetaminophen or ibuprofen, or decongestants like pseudoephedrine).
Precautions
Avoid alcohol and other CNS depressants. Use caution in patients with cardiovascular disease, asthma, COPD, and glaucoma. Caution in elderly patients due to increased sensitivity. Avoid driving or operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for diphenhydramine?
A: Adults: 25-50 mg orally every 4-6 hours, max 300 mg/day. Children (over 20 lbs): 12.5-25 mg orally every 4-6 hours, max 300 mg/day.
Q2: What are the common side effects of diphenhydramine?
A: Drowsiness, dry mouth, blurred vision, constipation, dizziness.
Q3: Can I take diphenhydramine if I am pregnant or breastfeeding?
A: Use with caution during pregnancy only if clearly needed. Contraindicated in breastfeeding mothers.
Q4: What are the serious side effects of diphenhydramine?
A: Allergic reactions, seizures, cardiac arrhythmias, confusion, hallucinations.
Q5: What medications should be avoided while taking diphenhydramine?
A: Alcohol, CNS depressants (benzodiazepines, opioids), MAOIs, anticholinergics.
Q6: Can diphenhydramine be used for motion sickness?
A: Yes, 25-50 mg orally 30 minutes before travel, then every 4-6 hours as needed.
Q7: What is the mechanism of action of diphenhydramine?
A: It is an H1 receptor inverse agonist, blocking the action of histamine. It also has anticholinergic and sedative effects.
Q8: Can diphenhydramine be used long-term for insomnia?
A: Long-term use is not recommended due to the development of tolerance and potential for dependence. Consult a physician for chronic insomnia.
A: Metabolized in the liver primarily by CYP2D6, eliminated by renal excretion.
Q10: What should I do if I experience an allergic reaction to diphenhydramine?
A: Seek immediate medical attention.
