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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
pressure.
Fast heart, blood pressure falls, irregular beats with alarming
palpitations.
Skin sensations local itching or burning sensation,
flushing and a disagreeable heat.
Stomach pain acid secretion increases; small intestine contracts with
crampy pain
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 allergic reactions.
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 also act on brain H1 receptors where they cause the sedative effect, 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. The powerful 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 with an
enviable safety record. These antihistamines have been marketed as allergy preparations
for the relief of hay fever and 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 effect such as sedation may be undesirable or 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 skin
itching. The sedating antihistamines are grouped into groups according to their chemical
structure. Here are some examples:
Class Generic (Proprietary)
with
Usual Adult Dose
Ethanolamines
Dimenhydrinate (Gravol) 50-100 mg qid
Diphenhydramine (Benadryl)
25-50 mg
qid
Alkylamines
Chlorpheniramine
(chlortipalon) 4 mg tid
Dexchlorpheniramine
2-4
mg tid
Phenothiazines
Promethazine
(Phenergan)
10-25 mg bid
Piperazines
Hydroxyzine (Atarax)
10-25 mg tid
Piperidines
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. An anticholinergic action may cause urinary retention and can
precipitate glaucoma.
Non- Sedating Antihistamines
Seldane, Claritin and Hismanal
*
were likely
to cause drowsiness than the older H1 blockers. Seldane and Hismanal have run 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
4 weeks
Loratadine (Claritin)
10 mg daily 1-2 hours
24 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 - a tricyclic antidepressant with marked antihistamine activity. Suitable for
administration at night. There is drug interaction with MAOIs, and can cause cardiac
arrthythmia. Dosage : 10 mg
H2-Receptor Blockers
The H2 receptor blocker, cimetadine, 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 combined.
Cimetidine - 400 mg bd
Ranitidine - 150 mg bd
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