Pharmacology of Diphenhydramine

Diphenhydramine is a first-generation antihistamine widely used for its efficacy in treating various allergic reactions, insomnia, and motion sickness.

Mechanism of Action

Diphenhydramine primarily functions by antagonizing the H1 (histamine 1) receptor, though it exhibits other mechanisms of action as well. The H1 receptor is found in numerous body tissues, including respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract, cardiac tissue, immune cells, the uterus, and central nervous system (CNS) neurons. Activation of these receptors leads to various actions like increased vascular permeability, vasodilation, and promotion of the allergic immune response.

As an inverse agonist at the H1 receptor, diphenhydramine reverses histamine’s effects on capillaries, thereby reducing symptoms of allergic reactions. Its ability to cross the blood-brain barrier allows it to inversely agonize CNS H1 receptors, causing drowsiness and suppressing the cough center in the medulla.

Additionally, diphenhydramine acts as an antimuscarinic, antagonizing muscarinic acetylcholine receptors, which lends to its use in antiparkinson medication. It also possesses local anesthetic properties due to its action as an intracellular sodium channel blocker.

Pharmacokinetics

Diphenhydramine is metabolized in the liver via the CYP450 enzyme system and is excreted in urine, both unchanged and as metabolites. It has a half-life ranging from 3.4 to 9.2 hours, with its peak serum time being around 2 hours post-administration.

Administration and Dosage

Diphenhydramine can be administered orally (tablet, capsule, solution), intramuscularly (IM), intravenously (IV), or topically.

Therapeutic Uses

• Allergies: Relief from sneezing, itching, watery eyes, and runny nose.
• Sleep Aid: Used to treat short-term insomnia.
• Motion Sickness: Prevents and treats symptoms such as nausea and dizziness.
• Common Cold: Reduces symptoms like sneezing and nasal congestion.

Adverse Effects

Common adverse effects include sedation, dizziness, impaired coordination, headache, dry mucous membranes, constipation, urinary retention, and hypotension. Serious reactions can include anaphylaxis, QT prolongation, arrhythmias, seizures, and toxic psychosis.

Cautions and Contraindications

Diphenhydramine should be used cautiously in patients with asthma, hyperthyroidism, cardiovascular disease, hypertension, or increased ocular pressure. It is contraindicated in patients with hypersensitivity to diphenhydramine, premature infants, neonates, and breastfeeding mothers.

Overdose and Toxicity

Overdose of diphenhydramine can lead to significant toxicity, including agitation, cardiac arrhythmias, rhabdomyolysis, and anticholinergic toxidrome. Treatment involves activated charcoal, benzodiazepines for agitation and seizures, sodium bicarbonate for widened QRS, and magnesium sulfate for prolonged QT interval.

Conclusion

Diphenhydramine is a versatile medication with a wide range of uses. However, its potential for adverse effects and toxicity, especially in overdose scenarios, necessitates careful monitoring and judicious use. Healthcare professionals must educate patients on the safe use of this medication, particularly when self-medicating.

References

1. NCBI Bookshelf. Diphenhydramine. NCBI Bookshelf
2. DrugBank Online. Diphenhydramine: Uses, Interactions, Mechanism of Action. DrugBank Online