Antihistamines primarily act to block histamine effects that
oc-cur in an immediate (type I) hypersensitivity reaction, commonly called an allergic reaction. They’re available
alone or in combina-tion products by prescription or over-the-counter.
Histamine-1 receptor antagonists
The term antihistamine
refers to drugs that act as histamine-1 (H1) receptor antagonists; that is, they compete with histamine for binding
to H1-receptor sites throughout the body. However,
they don’t displace histamine already bound to the receptor.
Based on chemical structure, antihistamines are
categorized into five major classes:
§ Ethanolamines include clemastine fumarate,
dimenhydrinate, and diphenhydramine hydrochloride.
§ Alkylamines include brompheniramine maleate,
chlorphenir-amine maleate, and dexchlorpheniramine maleate.
§ Phenothiazines include promethazine
§ Piperidines include azatadine maleate,
cetirizine hydrochloride, cyproheptadine hydrochloride, desloratadine,
fexofenadine hy-drochloride, loratadine, and meclizine hydrochloride.
§ Miscellaneous drugs, such as hydroxyzine
hydrochloride and hydroxyzine pamoate, also act as antihistamines.
antagonists are well absorbed after oral or parenteral administration. Some can
also be given rectally.
With the exception of loratadine and desloratadine,
antihistamines are distributed widely throughout the body and central nervous
Fexofenadine, desloratadine, and loratadine, which
are nonsedat-ing antihistamines, minimally penetrate the blood-brain barrier so
that little of the drug is distributed in the CNS, producing fewer ef-fects
there than other antihistamines.
Antihistamines are metabolized by liver enzymes and
excreted in urine; small amounts appear in breast milk. Fexofenadine, mainly
excreted in stool, is an exception. Cetirizine undergoes limited he-patic
antagonists compete with histamine for H1 receptors on effector cells (the cells that cause allergic symptoms),
blocking histamine from producing its effects. (See How chlorpheniraminestops an allergic response)
antagonists produce their effects by:
§ blocking the action of histamine on the small
§ decreasing dilation of arterioles and
engorgement of tissues
§ reducing the leakage of plasma proteins and
fluids out of the capillaries (capillary permeability), thereby lessening edema
§ inhibiting most smooth-muscle responses to
histamine (in par-ticular, blocking the constriction of bronchial, GI, and
vascular smooth muscle)
§ relieving symptoms by acting on the terminal
nerve endings in the skin that flare and itch when stimulated by histamine
§ suppressing adrenal medulla stimulation,
autonomic ganglia stimulation, and exocrine gland secretion, such as lacrimal
and salivary secretion.
Several antihistamines have a high affinity for H1 receptors
in the brain and are used for their CNS effects. These drugs include
diphenhydramine, dimenhydrinate, promethazine, and various piperidine
don’t affect parietal cell secretion in the stomach because their receptors are
H2 receptors, not H1.
Antihistamines are used to treat the symptoms of
type I hypersen-sitivity reactions, such as:
§ allergic rhinitis (runny nose and itchy eyes
caused by a local sensitivity reaction)
§ vasomotor rhinitis (rhinitis not caused by
allergy or infection)
§ allergic conjunctivitis (inflammation of the
membranes of the eye)
§ urticaria (hives)
§ angioedema (submucosal
swelling in the hands, face, and feet).
Antihistamines can have other therapeutic uses:
• Many are used primarily as
antiemetics (to control nausea and vomiting).
• They can also be used as
adjunctive therapy to treat an anaphylactic reaction after the serious symptoms are controlled.
• Diphenhydramine can help treat
Parkinson’s disease and druginduced extrapyramidal reactions (abnormal
• Because of its antiserotonin
qualities, cyproheptadine may be used to treat Cushing’s disease, serotonin-associated diarrhea, vascular
cluster headaches, and anorexia nervosa.
Antihistamines may interact with
many drugs, sometimes with life-threatening consequences:
• They may block or reverse the
vasopressor effects of epinephrine, producing vasodilation, increased heart rate,
and very low blood pressure.
• They may mask the toxic signs
and symptoms of ototoxicity (adetrimental effect on hearing) associated with
aminoglycosides or large dosages of
• They may increase the sedative
and respiratory depressant effects of CNS depressants, such as tranquilizers or alcohol.
• Loratadine may cause serious
cardiac effects when taken with macrolide antibiotics (such as erythromycin),
fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ciprofloxacin, and clarithromycin. (See Adverse reactions to antihistamines.)