Diphenhydramine - perhaps known most commonly as its brand name formulation Benadryl - is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes [
Diphenhydramine - perhaps known most commonly as its brand name formulation Benadryl - is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes [9, 10, 11, 15]. However, it also has antiemetic, antitussive, hypnotic, and antiparkinson properties [11, 14]. As histamine receptors exist both peripherally and in the central nervous system, diphenhydramine has been shown to cause sedation due to its competitive antagonism of histamine H1 receptors within the central nervous system [9, 10, 11, 15, 5]. While its use in allergy therapy can sometimes fall out of favor due to its sedative effect, diphenhydramine has been repurposed for use within many non-prescription over-the-counter sleep aids and cough-and-cold medications that have been marketed for "night time" use [9, 12, 13].
Diphenhydramine is also used in combination with [DB14132] as the anti-nausea drug [DB00985] where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system .
Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid . As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.
Diphenhydramine is a first-generation histamine H1 receptor antagonist (H1 antihistamine) that is wi...
Diphenhydramine is a first-generation histamine H1 receptor antagonist (H1 antihistamine) that is widely available as a non-prescription, over-the-counter (OTC) medication. As an OTC medication, diphenhydramine is typically formulated as tablets and creams indicated for use in treating sneezing, runny nose, itchy/watery eyes, itching of nose or throat, insomnia, pruritis, urticaria, insect bites/stings, allergic rashes, and nausea [9, 10, 11, 15, 5].
Additionally, when the use of oral diphenhydramine is impractical, there are also prescription-only formulations such as diphenhydramine injection products that are effective in adults and pediatric patients (other than premature infants and neonates) for:
i) the amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after acute allergic reaction symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated ;
ii) the active treatment of motion sickness ; and
iii) use in parkinsonism when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild cases of parkinsonism in other age groups, and in other cases of parkinsonism in combination with centrally acting anticholinergic agents . Read more
Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnot... Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties . The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone . Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere . Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone . Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain . Read more
Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors [
Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors [9, 10, 11, 15, 5]. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons [9, 10, 11, 15, 5]. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response [9, 10, 11, 15, 5].
Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms [9, 10, 11, 15, 5]. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center [9, 10, 11, 15, 5].
Furthermore, H1 receptors are similar to muscarinic receptors [9, 10, 11, 15, 5]. Consequently, diphenhydramine also acts as an antimuscarinic [9, 10, 11, 15, 5]. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication [9, 10, 11, 15, 5].
Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties . Read more
Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in app... Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour [6, 13]. The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration [6, 13]. Read more
Some prescribing information records the protein binding of diphenhydramine as approximately 78% [ Some prescribing information records the protein binding of diphenhydramine as approximately 78%  while others have suggested the medication is about 80 to 85%  bound to plasma proteins. Read more
Diphenhydramine is widely distributed throughout the body, including the CNS [ Diphenhydramine is widely distributed throughout the body, including the CNS . Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg . Read more
Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in... Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min . Read more
The elimination half-life ranges from 2.4-9.3 hours in healthy adults [ The elimination half-life ranges from 2.4-9.3 hours in healthy adults [16, 13]. The terminal elimination half-life is prolonged in liver cirrhosis . Read more
The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine [... The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine [12, 13]. Only about 1% of a single dose is excreted unchanged in urine [12, 13]. The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites [12, 13]. Read more
Overdose is expected to result in effects similar to the adverse effects that are ordinarily associa...
Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others [10, 11, 12, 13, 16]. Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes . Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse . Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow .
Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk . This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant .
Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults . Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects . Avoid use in elderly patients with confusion .
The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) .
After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease . However, the mean plasma clearance and apparent volume of distribution were not significantly affected .
LD50=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death. Read more
|Effect||Regions||Age Groups||Incidences||Evidence Type|
|Tightness of throat||US||
|Tightness of chest||US||
|Thickening of bronchial secretions||US||
|Dryness of nose dryness of throat||US||
- Avoid alcohol.
- Take with food.
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- 8 . Rodrigues WC, Castro C, Catbagan P, Moore C, Wang G: Immunoassay screening of diphenhydramine (Benadryl(R)) in urine and blood using a newly developed assay. J Anal Toxicol. 2012 Mar;36(2):123-9. doi: 10.1093/jat/bkr015. [PubMed: 22337782]
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- 10 . Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Tablets Patient Information [Link]
- 11 . Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Cream Monograph [Link]
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