Diphenhydramine

Drug name : Diphenhydramine

Trade name : Benadryl, Ikadryl, Diphenhydramine HCl (gen)

Classification :
Histamine H1 Antagonist

Dosage Form :

Use : Diphenhydramine
Diphenhydramine is an antihistamine used to relieve symptoms of allergy, hay fever, and
the common

cold.

These

symptoms

include rash, itching,

watery eyes,

itchyeyes/nose/throat, cough, runny nose, and sneezing. It is also used to prevent and
treat nausea, vomiting and dizziness caused by motion sickness. Diphenhydramine can also be
used to help you relax and fall asleep.

Mechanism of action : Diphenhydramine

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.
Drug characteristic : Diphenhydramine
Competes with histamine for H1-receptor sites on effector cells in the
Pharmacology

gastrointestinal tract, blood vessels, and respiratory tract; anticholinergic and

sedative effects are also seen
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

Pharmacodynamic
s

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 HAreceptors 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,

Distribution

although the exact mechanism is unknown.

Vd: Children: 22 L/kg (range: 15 to 28 L/kg); Adults: 17 L/kg (range: 13 to 20
L/kg); Elderly: 14 L/kg (range: 7 to 20 L/kg)
Extensively hepatic n-demethylation via CYP2D6; minor demethylation via

Metabolism

CYP1A2, 2C9 and 2C19; smaller degrees in pulmonary and renal systems;

Excretion
Duration of Action
Half-Life

significant first-pass effect

Urine (as metabolites and unchanged drug)
Histamine-induced flare suppression: 12 hours
Children: 5 hours (range: 4 to 7 hours); Adults: 9 hours (range: 7 to 12 hours);

Elimination
Protein Binding
Contraindications

Elderly: 13.5 hours (range: 9 to 18 hours)

98.5%
Hypersensitivity to diphenhydramine, other structurally related antihistamines, or
any component of the formulation; neonates or premature infants; breast-feeding
dverse events have not been observed in animal reproduction studies.
Diphenhydramine crosses the placenta. Maternal diphenhydramine use has

Pregnancy

generally not resulted in an increased risk of birth defects; however, adverse

events (withdrawal symptoms, respiratory depression) have been reported in
newborns exposed to diphenhydramine in utero

Safety factor for treatment: Diphenhydramine

Suf xes

R/ only

High alert

LASA
Ikaphen

Ikadryl injection Yes

No

injection,
Inovad injection

Storage
Store

at

room

temperature

away

from

moisture

and

light

Drug interaction: Diphenhydramine

Drug
Acetylcholinesterase
Inhibitors

Alcohol (Ethyl)

Reaction

Management

May diminish the therapeutic effect of Anticholinergic

Agents. Anticholinergic Agents may diminish the

Monitor therapy

therapeutic effect of Acetylcholinesterase Inhibitors.

CNS Depressants may enhance the CNS depressant effect

of Alcohol (Ethyl).

Monitor therapy

Amphetamines

May diminish the sedative effect of Antihistamines.

Monitor therapy

Anticholinergic Agents may enhance the adverse/toxic

Analgesics

effect of Analgesics (Opioid). Specifically, the risk for

(Opioid)combination.

constipation and urinary retention may be increased with

Monitor therapy

this
Anticholinergic
Agents

Betahistine

May enhance the adverse/toxic effect of other

Anticholinergic Agents.

Antihistamines may diminish the therapeutic effect of

Betahistine.

Monitor therapy

Monitor therapy

CYP2D6 Inhibitors (Moderate) may diminish the

Codeine

therapeutic effect of Codeine. These CYP2D6 inhibitors

may prevent the metabolic conversion of codeine to its

Monitor therapy

active metabolite morphine.

CYP2D6 Inhibitors (Moderate) may increase the serum
concentration of DOXOrubicin (Conventional).
DOXOrubicin

Management Seek alternatives to moderate CYP2D6

Consider therapy

(Conventional)

inhibitors in patients treated with doxorubicin whenever

modification

possible. One U.S. manufacturer (Pfizer Inc.) recommends

that these combinations be avoided.
Ipratropium (Oral
Inhalation)

May enhance the anticholinergic effect of Anticholinergic

Agents.

Avoid combination

Magnesium Sulfate

May enhance the CNS depressant effect of CNS

Depressants.

Monitor therapy

CYP2D6 Inhibitors may increase the serum concentration

of Metoprolol. Management Consider an alternative for
Metoprolol

one of the interacting drugs in order to avoid metoprolol

Consider therapy

toxicity. If the combination must be used, monitor response

modification

to metoprolol closely. Metoprolol dose reductions may be

necessary.
Anticholinergic Agents may enhance the ulcerogenic
Potassium Chloride

effect of Potassium Chloride. Management Patients on

drugs with substantial anticholinergic effects should avoid

Avoid combination

using any solid oral dosage form of potassium chloride.

RimabotulinumtoxinB

Anticholinergic Agents may enhance the anticholinergic

effect of RimabotulinumtoxinB.

Monitor therapy

may decrease serum concentrations of the active

metabolite(s) of Tamoxifen. Specifically, CYP2D6
Tamoxifen CYP2D6

inhibitors may decrease the metabolic formation of highly

Consider therapy

Inhibitors (Moderate)

potent active metabolites. Management Consider

modification

alternatives with less of an inhibitory effect on CYP2D6

activity when possible.
Thiazide and
Thiazide-Like
Diuretics

Tiotropium

Anticholinergic Agents may increase the serum

concentration of Thiazide and Thiazide-Like Diuretics.

Anticholinergic Agents may enhance the anticholinergic

effect of Tiotropium.

Monitor therapy

Avoid combination

CYP2D6 Inhibitors (Moderate) may diminish the

therapeutic effect of TraMADol. These CYP2D6 inhibitors
TraMADol

may prevent the metabolic conversion of tramadol to its

Monitor therapy

active metabolite that accounts for much of its opioid-like

effects.

Trimeprazine

May enhance the CNS depressant effect of CNS

Depressants.

Monitor therapy

Avoid use with

CNS Depressants may enhance the CNS depressant effect
of Zolpidem. Management Reduce the Intermezzo brand
Zolpidem

sublingual zolpidem adult dose to 1.75 mg for men who are

also receiving other CNS depressants. No such dose change
is recommended for women.

other CNS
depressants at
bedtime; avoid use
with
alcohol. Consider
therapy
modification

Rections should be monitoring: Diphenhydramine

Applies to diphenhydramine: compounding powder, injectable solution, oral capsule, oral
disintegrating strip, oral liquid, oral tablet, oral tablet chewable, oral tablet disintegrating

Nervous system
Nervous system side effects have been reported frequently. These have included
depression with drowsiness and sedation in nearly all patients treated. Motor skills may
be impaired. Dystonic reactions have been reported after single doses of
diphenhydramine

Hypersensitivity
Hypersensitivity side effects have included rash, pruritus and eczema. Photosensitivity
reactions have also been reported.
Gastrointestinal
Gastrointestinal side effects have been usually mild and included nausea and dry mouth.
Cardiovascular
Cardiovascular side effects have included hypotension, tachycardia, and palpitations.
Ocular
Ocular side effects have included blurred vision, diplopia, and dry eyes due to
anticholinergic effects.
Genitourinary
Genitourinary side effects have included urinary retention and dysuria as a result of the
anticholinergic effects of diphenhydramine.
Hematologic
Hematologic side effects such as hemolytic anemia, thrombocytopenia, and
agranulocytosis have been rarely caused by antihistamines

Parameter patients health : Diphenhydramine

Prevent the symptoms include rash, itching, watery eyes, itchyeyes/nose/throat, cough, runny
nose, and sneezing. The patient not nausea, vomiting and dizziness caused by motion sickness
and help patient relax and fall asleep.

Toxicity :
Concerns related to adverse effects:
CNS depression: May cause CNS depression, which may impair physical or mental abilities;
patients must be cautioned about performing tasks which require mental alertness (eg, operating
machinery or driving).
Disease-related concerns:
Asthma: Use with caution in patients with a history of asthma.

 Cardiovascular disease: Use with caution in patients with cardiovascular disease (including
hypertension and ischemic heart disease).
Increased intraocular pressure/glaucoma: Use with caution in patients with increased
intraocular pressure or angle-closure glaucoma.

Pharmaceutical Care :

When taking diphenhydramine, use caution driving, operating machinery, or performing

other hazardous activities. Diphenhydramine may cause dizziness or drowsiness. If you
experience dizziness or drowsiness, avoid these activities.

Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking
diphenhydramine.

Do not give this medication to a child younger than 2 years old.

For motion sickness, take diphenhydramine 30 minutes before you will be in a situation
that causes you motion sickness (such as a long car ride, airplane or boat travel,
amusement park rides, etc). Continue taking diphenhydramine with meals and at bedtime
for the rest of the time you will be in a motion-sickness situation.

As a sleep aid, take diphenhydramine within 30 minutes before bedtime.

Call your doctor if your symptoms do not improve after 7 days of treatment, or if you
have a fever with a headache, cough, or skin rash.

This medication can affect the results of allergy skin tests. Tell any doctor who treats you
that you are using diphenhydramine.

Reference :

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(1978)
4.

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13. Simons FER, Fraser TG, Reggin JD, Simons KJ "Comparison of the central nervous system
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