So when
Mr. Sneeze, with the help of Little Miss Sunshine, discovered that he had
allergies, it appeared that educating children about hay fever was the primary
goal of this 2003 children’s book. But it didn’t stop there. British pharmaceutical
company GlaxoSmithKline, who commissioned the book, took it one step too far
and slipped in a couple pages promoting their allergy medications, Piriton and
Piriteze.
In the story told by GSK, Mr. Sneeze may be better known as Mr. Sneak. |
The BMJ
article commented that adding to the controversy, the drugs GSK promoted were
no longer the first choice of pediatric antihistamines. As if the real travesty
was marketing an outdated product to
unsuspecting children and their parents. Nevertheless, the comment highlights a
key point: allergy medications have
improved drastically over the years, primarily increasing in safety, efficacy,
and ease of use.
The active
ingredient in GSK’s Piriton is chlorphenamine, a first generation antihistamine
(also found in Advil Allergy and Congestion, for example). Another
first-generation antihistamine is the ever-popular diphenhydramine, known by
most as Benadryl. These antihistamines are inverse agonists, meaning they work
by keeping the H1 receptor in its inactivated form, precluding the binding
of histamine. Although highly effective, first generation antihistamines are
plagued with strong sedative effects. This happens because they cross the blood
brain barrier (BBB), where they bind 50-90% of H1 receptors in the
central nervous system (CNS) and cause drowsiness. Diphenydramine is such a
strong sedative that it is FDA-approved for over-the-counter treatment of
insomnia.
The other drug advertised by Mr. Sneeze was Piriteze, which contains cetirizine, a less-drowsy second-generation antihistamine. Second-generation antihistamines, including cetirizine (Zyrtec), fexofenadine (Allegra), and loratidine (Claritin) penetrate the CNS poorly because they are pumped out by P glycoproteins, gatekeepers of the BBB. This greatly reduces the number of CNS H1 receptors that are occupied, with fexofenadine and loratidine binding negligibly and cetirizine binding up to 30% of the receptors. So, cetirizine may still cause drowsiness at recommended doses, whereas fexofenadine and loratidine should not. Second-generation antihistamines are generally preferred over first-generation for their enhanced safety profile.
P-glycoprotein’s command only works on better-behaved second generation antihistamines; the gatekeeper blind to first-generation antihistamines, which pass through the blood brain barrier. |
Yet
another treatment, allergen immunotherapy (allergy shots), may be appropriate
for allergy patients who have detectable specific IgE antibodies to relevant
trigger allergens. Specific immunotherapy (SIT) involves exposure to increasing
doses of specific allergen(s). The dose-increase phase usually lasts 14-28
weeks during which desensitization occurs, meaning cells become less reactive
or non-reactive to IgE-mediated immune responses. As
discussed previously, Type I hypersensitivity reactions are mediated by
T-helper 2 cells and allergy-prone infants have diminished
T-helper 1 reactions. Perhaps not surprisingly, successful immunotherapy is
associated with a shift towards a Th1-type reaction.
So, whereas
antihistamines and glucocorticoids treat allergy symptoms, SIT can actually
modify the disease and provide lasting protection against allergies.
Furthermore, it has been shown to prevent subsequent sensitization to new
allergens. In one study, 3 years of immunotherapy provided protection in some
patients for up to 12 years and reduced the occurrence of additional allergies
in almost half the patients.
Traditionally,
SIT is administered subcutaneously (under the skin) by injection. However, last
year three sublingual (under the tongue) allergen immunotherapy drugs were approved
by the FDA in rapid succession. Oralair, which contains 5 grass pollen extracts
(timothy, Kentucky blue, perennial rye, orchard and sweet vernal), became the
first FDA-approved
sublingual allergen extract. Eight days later, the FDA
announced approval of Grastek, which contains only timothy grass extracts.
Another 6 days later, Ragwitek
was approved for the treatment of short ragweed pollen allergies. Whereas
Oralair and Grastek are approved for pediatric use (10+ and 5+ years,
respectively), Ragwitek is for adults (18+) only. All drugs showed moderate
efficacy in clinical trials, with approximately 20-25% reduction in symptoms
and need for symptom-management medication during one allergy season, compared
to patients in the placebo group.
If needles aren’t your cup of tea, sublingual immunotherapy may provide a more palatable option. |
Some
people want a spoonful of sugar to help the medicine go down…or perhaps a
spoonful of honey in place of medication entirely. Anecdotal evidence suggests
that eating local, unfiltered raw honey can have similar effects to SIT by
desensitizing the immune system. The idea is logical: bees incorporate pollen into honey;
therefore, eating local, unprocessed honey will expose you to the pollen
prevalent in your area. Only a few
studies have addressed the efficacy of honey for allergy treatments; one
lasted only 10 days (no reduction in allergies observed) or used birch
pollen-spiked honey for 5 months (effective at reducing allergies). Unfortunately,
neither of these studies properly evaluated honey as an allergy treatment. The
first had the right idea, but desensitization requires months (not days) to be
effective, and while the second study demonstrates the feasibility of the idea,
artificially-spiked honey does not address the real question.
Despite
the shortcomings of these studies, the
reason honey will never be recommended for allergy treatment is also logical: the types of pollen bees primarily use are
from fragrant flowers, not the wind-carried pollen from grasses like timothy
and ragweed or trees like birch, which are responsible for the majority
of allergies. Furthermore, the dose of any allergenic pollen in honey is
very low and not controlled, making it virtually impossible to achieve
desensitization analogous to that observed with SIT.
Searching for an allergy cure in a “hunny” jar will only get you sticky…you’d be better off sticking your head in it to reduce your exposure to wind-carried pollen. |
Contributed
by: Julia van Rensburg, PhD
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Nasser S, Vestenbaek U, Beriot-Mathiot A, & Poulsen PB (2008). Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma. Allergy, 63 (12), 1624-9 PMID: 19032235
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