Why do some cold/flu meds make us drowsy (sleepy)?

When I was little, my mom would tell me that doctors put "sleepy stuff" inside our flu and cold therapy because we needed rest. That made a lot of sense, until I started to need to actually function even when I was sick. Then, I thought why didn't they just leave the sleepy stuff out for those who needed to function?

It turns out that things didn't work that way. Doctors didn't add anything to flu/cold remedies, and instead, these drowsy properties were innate to the chemical compound itself. Sounds a bit complicated? Let's see if we can simplify things.

Firstly, let me introduce you to our "Blood Brain Barrier", or BBB. Our BBB acts like a force field around our brain. It protects our brain from most harmful agents in our plasma, and also from drastic changes in plasma compositions. Plasma is the liquid part of blood that carries hormones, sugar, cholesterol, electrolytes etc etc. That way, a lot of medicine cannot cross this barrier, protecting our brain from its effects.

There are exceptions though. Our super force field isn't really impenetrable. 1st generation antihistamines like Chlorpheniramine (Piriton) and Diphenhydramine (Benadryl) are what we call lipophilic compounds. (Lipophilic means that they can dissolve in oil better than in water). Lipophilic compounds can cross the BBB much better than their ionic counterparts. Therefore, 1st gen antihistamines can cross the BBB rather freely.

So the molecules of 1st gen antihistamines are free to bind to histamine receptors in our brain, which makes us lethargic and sleepy, or drowsy.

This is why the pharmacist will always tell you not to operate heavy machinery after taking these type of medicine.

But nowadays, scientists have come up with 2nd and 3rd generation antihistamines. Examples of the newer antihistamines are like cetirizin (Zyrtec), Loratadine (Clarityne), Levocetirizin (Xyzal) and Fexofenadine (Telfast). They made the medicine Ionic instead of liphophilic. Because these molecules are ionic, they cannot penetrate the BBB very well. As a result, only about 7-12% of the molecules manage to penetrate the BBB. They still work perfectly on the rest of our body (nose, skin etc), but doesn't affect our brain like the 1st generation counterparts do.

So, to put it simply, some meds put you to sleep because they cross the BBB. Those that act only on the body don't make us drowsy.

Oh, and before we end, we need to put to rest the age old myth that "Drowsy medicine is better for you, and makes you heal faster". There is simply no truth in that, and most evidence support the longer lasting effects of the newer generation, and fewer side effects. Therefore I would prefer a newer non-drowsy cough/cold medicine most of the time.