The P-I-E-N-O Parkinsn's List Drug Database
diphenhydramine/ BenadrylTM , DiphedrylTM
ANTIHISTAMINE/anticholinergic
Description: Diphenhydramine is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In general, gastrointestinal side effects are minimal. Diphenhydramine is a popular antihistamine due to its relative safety after parenteral administration. In addition to the usual allergic symptoms, the drug also treats irritant cough, although the drying effect may be counterproductive. Diphenhydramine is effective in the relief of 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. Diphenhydramine was originally approved by the FDA in 1946 as a prescription-only drug but was later changed to OTC status. Due to its ability to induce drowsiness, it is also promoted as an OTC hypnotic.
Mechanism of Action: 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.
Antihistamines also possess anticholinergic properties in varying degrees; 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. Diphenhydramine has a direct suppressive action on the cough center and causes sedation via CNS depression. Topical diphenhydramine provides local relief from insect bites, minor burns, sunburn, or minor abrasions, possibly due to an anesthetic effect resulting from decreased permeability of nerve cell membranes to sodium ions (preventing the transmission of nerve impulses). Following prolonged administration of diphenhydramine, tolerance can occur, but this may be beneficial because of reduced sedative effects.
Pharmacokinetics: In general, antihistamines are well absorbed from the GI tract, but different antihistamines vary in solubility, which affects the onset of action. Less soluble antihistamines have a slower onset of action and are less likely to cause toxicity. Onset of action of diphenhydramine occurs in about 15-30 minutes, with peak concentration occurring in about 2-4 hours. The duration of action ranges from 4-6 hours. Diphenhydramine is highly protein-bound. It is widely distributed in body tissues and fluids, and it crosses the placenta and is excreted into breast milk.
Metabolism occurs in the liver to produce diphenylmethoxyacetic acid, which may be conjugated; other metabolites are also formed. Plasma half-life is between 2-8 hours. Excretion, consisting of unchanged drug and metabolites, is primarily renal and occurs within 24-48 hours of dosage.
CONTRAINDICATIONS/PRECAUTIONS: Diphenhydramine is relatively contraindicated in patients with asthma and COPD, especially during acute attacks, because anticholinergic actions may thicken secretions and reduce expectoration.
Diphenhydramine is classified as pregnancy category C. Antihistamines generally are not recommended for use in pregnancy, especially during the third trimester, because there is a risk of seizures in the fetus. Risks-benefits should be considered during pregnancy and in women expecting to become pregnant. Antihistamines are contraindicated for use in women who are breast-feeding because they can induce hyperexcitability in the infant, seizures in premature infants, and inhibited lactation. Alternative methods of feeding are recommended if diphenhydramine therapy is deemed necessary.
Diphenhydramine should be used with extreme caution in children. Children can experience paradoxical CNS stimulation and should be supervised in their activities to ensure safety. Some children have experienced respiratory depression and sleep apnea while taking antihistamines; SIDS has occurred. The drug should be used with extreme caution in children with a family history of SIDS or sleep apnea. Antihistamines are contraindicated in neonates because they may experience paradoxical CNS stimulation and there is an increased risk of seizures.
Diphenhydramine should be used with extreme caution in patients predisposed to or with closed-angle glaucoma. Due to its anticholinergic actions, it can increase intraocular pressure, precipitating an acute attack of glaucoma. Diphenhydramine must also be used cautiously in patients with open-angle glaucoma; glaucoma therapy may need to be adjusted.
Diphenhydramine should be used cautiously in patients with hepatic disease. Diphenhydramine is extensively metabolized in the liver, hepatic impairment may lead to a decrease in metabolism, a subsequent increase in drug levels, and an added risk of toxicity.
Because of anticholinergic effects, diphenhydramine should be used with extreme caution in patients with bladder obstruction, GI obstruction, prostatic hypertrophy, or urinary retention. Antihistamines have a quinidine-like action as well as anticholinergic action, and should be used with caution in patients with cardiac disease because they can cause tachycardia, palpitations, and/or arrhythmias.
Diphenhydramine should be used with caution in patients with hyperthyroidism or hypertension since it can exacerbate these conditions.
Antihistamines should be used with caution in patients undertaking tasks requiring mental alertness. Drowsiness can be severe in some patients. Adverse effects are more likely to occur in geriatric patients. Patients should exercise extreme caution until the effects are known. Alcohol can add to sedation caused by diphenhydramine.
In addition, antihistamines can mask signs of allergic reactions, thus delaying the diagnosis of a hypersensitivity reaction.
DRUG INTERACTIONS: If diphenhydramine is used concomitantly with other CNS depressants, additive CNS effects, such as drowsiness and sedation, can occur. Patients taking diphenhydramine should be warned not to self-medicate with with ethanol; barbiturates; anxiolytics, sedatives, and hypnotics; or other HA-blockers.
MAOIs can increase and prolong anticholinergic and CNS depressant effects of diphenhydramine. Their concurrent use is not recommended.
Other drugs that have anticholinergic activity can add to the anticholinergic side effects of diphenhydramine. These drugs include tricyclic antidepressants, direct anticholinergics, and phenothiazines. Diphenhydramine often is used to treat extrapyramidal symptoms associated with phenothiazine or butyrophenone therapy.
Diphenhydramine administered with thyrotropin-releasing hormone, TRH can increase serum amylase and prolactin concentrations.
ADVERSE REACTIONS: CNS depression, manifested as drowsiness, sedation, and/or dizziness, can occur during therapy with diphenhydramine. There is considerable individual patient response to sedative effects, so patients should be warned of the possible impairment of mental acuity. These side effects may disappear after a few days of medication. Geriatric patients may be more disposed to adverse CNS depressant effects, and alcohol intake will increase sedation. If symptoms persist or are severe, a dose reduction or switch to another antihistamine may be advisable. Other possible CNS effects include headache and hallucinations.
Antihistamines sometimes can cause CNS stimulation. This effect is more likely to occur in children with overdoses, and symptoms may include restlessness or akathisia, insomnia, palpitations, and seizures.
Diphenhydramine possesses a moderate degree of anticholinergic actions. Anticholinergic effects that can occur during therapy include thickening of bronchial secretions, xerostomia, urinary retention, insomnia, nervousness, dysuria, and/or blurred vision. Geriatric patients are more likely to experience such adverse reactions.
Antihistamines may cause adverse GI effects including nausea/vomiting, diarrhea, constipation, abdominal pain, and/or anorexia. Some of these adverse reactions may be relieved by taking the drug with meals or milk.
Adverse cardiovascular responses are likely to be associated with the anticholinergic properties or the quinidine-like anesthetic effects of antihistamines. These responses can include sinus tachycardia, extrasystoles, palpitations, and/or cardiac arrhythmias. Alpha-adrenergic blockade can lead to symptoms of hypotension. Hypertension can also occur.
Topically application of diphenhydramine can result in a hypersensitivity reaction. Allergic contact dermatitis has been reported and is manifested by inflammation, pruritus, and eczema.
PATIENT INFORMATION:
What do diphenhydramine tablets or capsules do?
Diphenhydramine (BenadrylTM ) is an antihistamine that has many uses. It relieves irritant cough, symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions, motion sickness and vertigo (dizziness and loss of balance), and Parkinson's disease. Generic diphenhydramine tablets or capsules are available, with or without a prescription.
What should my doctor, dentist or pharmacist know before I take diphenhydramine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take diphenhydramine tablets or capsules by mouth. Follow the directions on the prescription label. Take diphenhydramine with food or milk if it upsets your stomach. Take your doses at regular intervals. Do not take your medicine more often than directed.
If you are taking diphenhydramine to stop you getting car (or travel) sick, take the first dose 30 to 60 minutes before you leave.
Special precautions for use in children:
Diphenhydramine is not for children under 6 years old, unless prescribed by the doctor.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double doses.
What other medicines can interact with diphenhydramine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking diphenhydramine?
Serious side effects with diphenhydramine include:
Call your doctor as soon as you can if you get any of these.
Minor side effects with diphenhydramine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take diphenhydramine?
Tell your doctor if your symptoms do not improve in 1 or 2 days.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how diphenhydramine affects you. To reduce the risk of dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.
Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature, between 15 and 30C (59 and 86F). Protect from moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.
Parkinsn's Archive Treasures Page
John Cottingham is the webmaster of this site.
