Histamine and Antihistamines
Almost everyone has taken an antihistamine to treat hay fever, itching, to
relieve nausea and vomiting, in tablets and syrups used to treat cough and cold
symptoms, or as an aid to sleep. The popularity of antihistamines is a mute
testimony to the diverse negative effects of histamine. To get a good idea of
what histamine can do, let us imagine the effects of an injection of a small
amount of histamine:
Histamine symptoms might include:
Headache is felt as a pulsating, whole-head pain, often with a sense of
Fast heart, blood pressure falls, irregular beats with alarming palpitations.
Skin sensations local itching or burning sensation, flushing and a
Stomach pain acid secretion increases; small intestine contracts with
Respiratory - nose swelling, congestion, sneezing and wheezing.
Anxiety and agitation with diffuse, deep, odd body sensations:"...my bones are
on fire", "I feel weird all over", "...a deep pricking, crawling sensation...".
Histamine carries its message to a large number of cells by attaching to a
special receptor on the cells' surfaces. There are two kinds of histamine
receptors, H1 and H2. These receptors both receive histamine as a messenger, but
the meaning conveyed is different.
H1 receptors tend to produce the symptoms already listed and activate
H2 receptors tend to act as negative feedback receptors and turn the
allergic reaction off. They also activate the acid-producing, parietal cells of
the stomach lining.
Histamine dilates blood vessels and acts with prostaglandins, PGE2 and PGI2,
to produce the early swelling, redness and heat of an inflammatory response. The
same mediators may sensitize nerve endings to other pain-producing mediators
such as bradykinin. An initial burst of mediator activity will often set a
series of cell responses in motion which will amplify and prolong disturbances.
Once inflammation is established in tissues by immune cell invasion and mediator
release, recovery may take several days to weeks.
Antihistamines are drugs which block the receptors so that the
histamine messages are not received. We have drugs that selectively block both
kinds of histamine receptors. The common antihistamines (Benadryl,
Chlortripalon, Atarax, Claritin, Seldane, and Hismanal) are H1 blockers. The H1
block is useful to treat allergic reactions. The older sedating antihistamines
have been used for years and are cheap and effective.
The sedating group act on brain H1 receptors where they cause sedative
effects, a dangerous effect if you are driving, operating machinery, or
otherwise need to be alert and vigilant. Antihistamine sedative effects are
increased by concurrent alcoholic beverage ingestion and by a long list of
psychotropic drugs. The sedative effects of some foods such as milk and wheat in
susceptible people is not blocked, but enhanced by antihistamines.
The classic antihistamines are represented by chlorpheniramine (
Chlor-Tripalon), brompheniramine (Dimetane), diphenhydramine ( Benadryl) and
dimenhydrinate (Gravol). All have been in common use for 40 years. These antihistamines have been marketed as allergy
preparations for the relief of hay fever and hives and other itchy skin
conditions. Antihistamines are included in over-the counter cold and cough
preparations even though there is little evidence of benefit and unwanted side
effects such as sedation can be risky.
Gravol is marketed as an anti-nausea drug although it is a typical
antihistamine. Benadryl has been used as a sedative infants and children,
although the occasional child will become restless or hyperactive after taking
it. A single bedtime dose of 8.0 mg of chlopheniramine will block allergy
symptoms for 24 hours and is often adequate for hay fever relief or relief from
The sedating antihistamines are derived from different chemical groups. Here
are some examples:
Dimenhydrinate (Gravol) 50-100 mg qid
Diphenhydramine (Benadryl) 25-50 mg qid
Chlorpheniramine (chlortipalon) 4 mg tid
Dexchlorpheniramine 2-4 mg tid
Promethazine (Phenergan) 10-25 mg bid
Hydroxyzine (Atarax) 10-25 mg tid
Cyproheptadine (Periactin) 4 mg tid
Azatadine (Zadine) 1-2 mg tid
Unwanted effects are common with these antihistamines, the commonest being
sedation, dizziness fatigue, insomnia and dry mouth. Paradoxical hyperactivity
occurs in some children. Alcohol increases the sedative effects of these
drugs and users are advised to abstain from drinking while on antihistamine
therapy. The ability to drive and operate machinery is impaired and should
be avoided. Anticholinergic action may cause urinary retention, precipitate
glaucoma, and aggravate dementia.
Seldane, Claritin and Hismanal were less likely to cause drowsiness
than the older H1 blockers. However, Seldane and Hismanal ran into big problems
with adverse effects.
The following drugs are shown with generic name, trade name, common dose,
onset and duration of action.
Terfenadine (Seldane)* 60 mg bd 1-2
hours >12 hours
Astemazole (Hismanal) * 10 mg daily 1-2 hours
Over the Counter, generally recognized as safe.
Loratadine (Claritin) 10 mg daily 1-2 hours
Cetirizine (Reactine) 10 mg daily
1-2 hours 24 hours
Fexofenadine ( Allergra)
* Seldane and Hismanal have been withdrawn from the US market and placed on
prescription drug status in Canada because of rare fatal ventricular arrythmias
reported with larger than normal doses, in patients with liver disease and when
the drugs were administered along with erythromycin, ketoconazole and other
drugs. Seldane has been replaced by Fexofenadine ( Allergra), a metabolite of
terfenadine with no know cardiac effects. It is non-sedating. Claritin
remains a top selling drug.
Other antihistamines and related drugs :
Ketotifen Adult dosage : 1-2 mg bd.
Tricyclic antidepressants - most of the first and second generation
antidepressants have antihistaminic activity. Doxepin is a tricyclic
antidepressant with marked antihistamine activity. Suitable for administration
at night. There is drug interaction with MAOIs, and can cause cardiac
arrhythmia. Dosage : 10 mg
The H2 receptor blocker, cimetidine, first marketed as "Tagamet", joins
Valium as one of the best-selling drugs of all time. The H2 block reduces
stomach acid secretion. This acid reduction helps to prevent and to heal peptic
ulcers. Cimetadine may be thought of as an allergy reaction modifier and antacid
Cimetidine - 400 mg bd
Ranitidine - 150 mg bd