Trevor's Best Friend

(This blog post is dedicated to Trevor, Daphne, and anyone else that is suffering from allergies while on this trip. But especially Trevor.)

           

            It kind of took me a while to figure out what I think I want to do with my life. For a lot of my younger years, I thought that I’d want to own a restaurant like my dad. Fortunately, during my early high school years, after seeing how stressed my dad always is thanks to his job, I came to my senses and decided to try to find a career path that would let me do things I enjoyed and really wanted to do. I knew that I’d liked science forever, ever since I was a little kid that played with science-in-a-box kits when I was bored, and, in high school, I discovered that I really liked chemistry and biology. I also knew that I really enjoyed helping people when they had problems. It took me until junior year, however, before I figured out the best way to combine these two desires.  Perhaps (and by “perhaps,” I mean “almost definitely, because of them asking for what I wanted to do later in life”) it was because of college apps looming over my head, or maybe it was because I’ve been taking asthma and allergy medications all my life, but I decided that I wanted to enter the pharmaceutical research field, focusing on cancer treatments, as the diseases is very prevalent in my family.  

            Needless to say, I’m really excited for Dr. Blakey’s pharmaceutical chemistry unit in our Chem 468 class. We’ve been talking about the drug discovery pathway recently, but all this talk of medicines made me want to learn about how some of the medications I use actually work, so I looked up the mechanism for one of my favorite drugs: diphenhydramine HCL, more commonly known as Benadryl, a drug I’ve taken more times than I can remember to treat my allergies.

To understand diphenhydramine, we first must understand what allergies are. That stuffy nose or closing windpipe is a result of our immune system overacting to a protein associated with a substance that is actually harmless, such as dust mites or mold. The immune system is composed of all kinds of cells that have the goal of keeping us safe from invaders, but, to understand allergies, we need only to learn about B-lymphocytes (B-Cells) and IgE antibodies. B-cells are like the body’s policemen. They patrol around our blood stream looking for foreigners, and they check them out to make sure they are all good (Okay, maybe that’s only the police in Arizona, but you get the idea). Most things get checked out and are free to go with no problem. Intruders, however, cause B-cells to set off the alarm and produce antibodies, Y-shaped carbohydrates that can stick to particles or micro-organisms (the antigen) to act as markers, or, if a lot of them stick to the antigen, totally neutralize its functionalities. There are five types of antibodies, also known as immunoglobulins (Igs), but we just have to focus on IgE to understand allergies.

 

An Antibody

            When the B-cells of a person with allergies encounter an antigen that triggers an allergic response, lots of IgE is produced, and they bind to mast cells and basophils – two cells that contain a compound called histamine - in various locations throughout the body during what is called the “sensitizing exposure.” After about ten days’ worth of sensitizing exposure, mast cells and basophils will be primed with enough histidine to trigger its immediate release the next time the antigen is encountered, triggering an allergic cascade.  

            First in an allergic cascade, the IgE antibodies bound to the basophils and mast cells recognize the proteins on the surface of the antigen (the allergen) and bind to them while remaining attached to the mast cells / basophils. This causes a family of about 20 proteins called the complement complex to activate. The first complement protein will attach itself to a site on the antibody-bound antigen, then the second complement protein will attach itself to the first, so on and so forth. When all the proteins are attached to each other, the mast cell / basophil is destroyed, releasing the histamine contained within it into the blood and surrounding tissues.

            Once released, there are four receptors on cells that histamine can bind to: H1, H2, H3, and H4. H1 is the receptor we are concerned with; when Histamine binds to H1, inflammation associated with allergy attacks occurs. In other words, Histamine binding to H1 triggers runny noses, watery eyes, and itchy skin, amongst other symptoms.

            The way Benadryl and other antihistamines work is rather simple: they competitively inhibit Histamine at the H1 receptor. In other words, diphenhydramine binds to H1 receptors before Histamine can. Since Histamine cannot bind to the H1 receptor anymore, it cannot trigger an allergic response. This makes sense, since both molecules contain nitrogen and sites for Hydrogen boding to occur (see below).

           

Diphyhdramine

Histamine

            In short, Benadryl really is what its slogan says it s: “The Histamine Blocker.” (Unless you’re Trevor. Then, not even the Histamine blocker seems to work for you…)

Works Referenced:

http://science.howstuffworks.com/environmental/life/human-biology/allergy.htm

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/histamine.html

http://www.ehow.com/how-does_5173286_histamine-work_.html

http://www.webmd.com/allergies/guide/antihistamines-for-allergies