[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/) › Diphenhydramine

# Diphenhydramine

## H1 antihistamines?

H1 antihistamines

The classic sedating first-generation antihistamine: allergy, sleep, motion sickness and drug-induced dystonia, with strong anticholinergic effects.

Updated Nov 1, 2026

## Quick facts

**Group**
[H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/)

**Target**
Histamine H1 receptor

**Used for**
Allergy and cold symptoms · Anaphylaxis

**Key effects**
Drowsiness and slowed reactions · Dry mouth

**Monitor**
Level of sedation and breathing

**ATC**
R06AA02

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**Histamine H1 receptor**Diphenhydramine

ⓘ The figure shows doxepin, a tricyclic first-generation H1 blocker, in the human H1 receptor; diphenhydramine binds the same site.

**Target in 3D:** Histamine H1 receptor. PDB structure 3RZE (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3RZE) · Drag to rotate · pinch to zoom

Diphenhydramine is an ethanolamine H1 inverse agonist that crosses the blood–brain barrier easily. Blocking central H1 receptors causes sedation; blocking muscarinic receptors gives anticholinergic effects that are useful against motion sickness and drug-induced parkinsonism or dystonia, but cause dry mouth, urinary retention and confusion. It also blocks sodium channels, which gives local anaesthetic action and explains the wide-QRS arrhythmias of overdose.

- Diphenhydramine enters the brain easily
- It blocks central and peripheral H1 receptors: sedation, less allergy
- It also blocks muscarinic receptors: dry mouth, less nausea
- In overdose, sodium-channel block widens the QRS

## Indications

- Allergy and cold symptoms: sneezing, runny nose, itchy eyes [Allergic rhinitis →](https://durgical.com/en/conditions/allergic-rhinitis/)
- Anaphylaxis, as an add-on to epinephrine once the acute symptoms are controlled [Anaphylaxis →](https://durgical.com/en/conditions/anaphylaxis/)
- Motion sickness
- Drug-induced parkinsonism and acute dystonia (injection)
- Short-term insomnia in adults (not to make children sleep) [Insomnia disorder →](https://durgical.com/en/conditions/insomnia-disorder/)

## Adverse effects

### Common

- Drowsiness and slowed reactions
- Dry mouth, blurred vision and constipation
- Urinary retention, especially with an enlarged prostate
- Dizziness and poor coordination

### Serious (rare, important)

- Confusion, delirium and falls in older adults
- Paradoxical excitation, hallucinations and seizures in children
- Overdose: anticholinergic syndrome, seizures, wide-QRS arrhythmias
- Tissue necrosis if the injection is used as a local anaesthetic

## Contraindications

- Newborns and premature infants
- Breastfeeding (injection label)
- Use as a local anaesthetic (risk of local necrosis)
- Caution in angle-closure glaucoma, prostate enlargement or bladder outlet obstruction
- Older adults: avoided where possible because of confusion, falls and urinary retention

## Key interactions

**Alcohol, benzodiazepines, opioids and other CNS depressants**
Additive sedation and slowed breathing

**Other anticholinergic drugs (tricyclic antidepressants, oxybutynin, antipsychotics)**
Additive dry mouth, urinary retention, constipation and confusion

**MAO inhibitors**
Prolong and intensify the anticholinergic effects

## What is monitored

- Level of sedation and breathing, especially with other depressants
- Urine output and bowel habit
- Confusion and fall risk in older adults

## Administration and safety

- Oral, intravenous (slowly) or deep intramuscular; never as a local anaesthetic injection
- It is in many night-time cold and sleep products: check labels to avoid double dosing
- Not used to make a child sleep

## Pregnancy and breastfeeding

Diphenhydramine has long pregnancy use; it is avoided near delivery and in breastfeeding because newborns are very sensitive to antihistamines.

## Nursing care

- Check breathing and sedation after injection; raise bed rails and assist walking
- Watch for urinary retention and constipation, especially in older men
- In anaphylaxis, make sure epinephrine has been given first
- Teach not to drive or operate machinery until the effect is known, and to avoid alcohol

## Pharmacokinetics

**Absorption**
Well absorbed by mouth; also given intravenously or intramuscularly

**Distribution**
Widely distributed, including the brain

**Metabolism**
Liver, with first-pass metabolism

**Elimination**
As metabolites in the urine

**Onset and duration**
Sedation and relief within an hour by mouth, faster by injection

## Memory aid

DIPHENhydramine = DIzzy, Dry, Drowsy: the three Ds of a first-generation antihistamine.

## Test yourself

Think of the answer, then tap the question to see it.

## Why is diphenhydramine on lists of drugs to avoid in older adults?

Its anticholinergic and sedative effects cause confusion, falls, constipation and urinary retention.

## Which property of diphenhydramine helps treat acute dystonia from antipsychotics?

Its central antimuscarinic (anticholinergic) action.

## What ECG change suggests a dangerous diphenhydramine overdose?

A widened QRS from sodium-channel blockade.

## What is the role of diphenhydramine in anaphylaxis?

Only an add-on for itching and hives after epinephrine.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/diphenhydramine/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 4

- [Promethazine](https://durgical.com/en/pharmacology/promethazine/)
- [Hydroxyzine](https://durgical.com/en/pharmacology/hydroxyzine/)
- [Chlorphenamine](https://durgical.com/en/pharmacology/chlorphenamine/)
- [Loratadine](https://durgical.com/en/pharmacology/loratadine/)

## Related conditions 3

- [Allergic rhinitis](https://durgical.com/en/conditions/allergic-rhinitis/)
- [Anaphylaxis](https://durgical.com/en/conditions/anaphylaxis/)
- [Insomnia disorder](https://durgical.com/en/conditions/insomnia-disorder/)

[← Back to the class: H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - DIPHENHYDRAMINE HYDROCHLORIDE injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=af972e71-62ab-40c6-925a-cbcb4d6720a4) (DailyMed (U.S. National Library of Medicine), 2026); [Diphenhydramine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682539.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=R06AA02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/diphenhydramine/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/diphenhydramine/