indication

For the treatment of symptoms associated with Vertigo/Meniere's disease, nausea and vomiting, motion sickness and insect bite.

pharmacology

Diphenhydramine is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, diphenhydramine competes with free histamine for binding at HA-receptor sites. Diphenhydramine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of diphenhydramine. This anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.

mechanism of action

Diphenhydramine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.

toxicity

LD₅₀=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

biotransformation

Hepatic and renal

absorption

Quickly absorbed with maximum activity occurring in approximately one hour.

half life

1-4 hours

route of elimination

Little, if any, is excreted unchanged in the urine; most appears as the degradation products of metabolic transformation in the liver, which are almost completely excreted within 24 hours.

drug interactions

Atomoxetine: Diphenhydramine, a moderate CYP2D6 inhibitor, may increase the therapeutic and adverse effects of atomoxetine by decreasing its metabolism.

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Rivastigmine: Possible antagonism of action

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Diphenhydramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Tamoxifen: Diphenhydramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Diphenhydramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Diphenhydramine is initiated, discontinued, or dose changed.

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Tramadol: Diphenhydramine may decrease the effect of Tramadol by decreasing active metabolite production.

Trimethobenzamide: Trimethobenzamide and Diphenhydramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Diphenhydramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Diphenhydramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.