Now that we’ve gone over some basic information regarding the nomenclature of drugs,
their administration, as well as some of the ways they move through
and interact with the body, we are ready to dive into an extensive survey of drugs.
This is quite a daunting task, since there are hundreds of drugs that deserve to be covered.
There are also several ways this survey could be approached. As we know, drugs
can be categorized by molecular structure, but they can also be categorized in the context of
therapeutic classification, meaning what they treat, as well as pharmacological classification,
meaning how they work. In the interest of being thorough, we will touch on all of these methods
of categorization to some extent as we go. But to start out, let’s get our feet wet
with a class of drugs that almost everyone is familiar with in one form or another.
We’ve all experienced the aches and pains of inflammation, headache, and fever, as these are a
part of life. To relieve these symptoms, millions of us reach for common over-the-counter medicines
like aspirin, Advil, Motrin, and Aleve. But where did these drugs come from and how do they work?
This has actually been discussed at great length over in the History of Drugs series,
but to briefly paraphrase, Hippocrates was an ancient Greek physician, and he found that chewing
on willow tree bark was effective in reducing fever. It wasn’t until 1828 that a compound,
salicin, was isolated from those leaves by Johann Büchner, a professor at the University of Munich.
By 1829, French pharmacist Henri Leroux was using a purified form of salicin to treat arthritis,
but it wasn’t well tolerated by patients. Later that century, a fairly young company named Bayer
Pharmaceuticals modified the compound to produce acetylsalicylic acid. This is what we commonly
refer to as aspirin, which was first brought to market in 1899. Bayer was incredibly successful
with the product, and today the market for aspirin and similar drugs is worth roughly $15 billion in
sales, expected to grow to $24 billion by 2027. Aspirin, along with similar drugs such as Advil,
Motrin, and Aleve, all belong to a class of drugs called NSAIDs, which stands for nonsteroidal
anti-inflammatory drugs. They are widely used because of their three important properties.
They are antipyretic, meaning they reduce fever, analgesic, lowering the amount of pain we feel,
and anti-inflammatory, reducing inflammation, an important part of the immune response.
This makes these drugs popular options in the treatment of inflammatory diseases like arthritis
or tendonitis, and also to lower fever. In addition, at low doses, NSAIDs can prevent
clotting of the blood, making them important treatments for people with cardiac disease.
So how exactly do NSAIDs achieve these results? They work by inhibiting the function of two
enzymes: cyclooxygenase 1 and 2, or COX-1 and COX-2 for short. In the body, COX enzymes perform
the first two enzymatic reactions in a pathway converting arachidonic acid within the body into
a series of compounds called prostaglandins, which are involved in many of our bodily functions.
COX-1 is always working to make a group of prostaglandins which serve a host of
“housekeeping” functions such as regulating the mucous lining of our gut and the clotting activity
of our blood. COX-2, however, turns on and generates select prostaglandins in response to the
needs of our bodies. In response to inflammation, in particular, COX-2 generates prostaglandins that
intensify the symptoms of inflammation. We have all experienced the effects of
inflammation. After an injury or infection, the body must contain and repair the affected area.
Blood vessels in the area of injury become leaky, allowing immune cells traveling in
the blood to leave the vessels and enter the injured site to fend off any infectious agents.
This increase in blood flow and infiltrating immune cells causes the redness, warmth,
pain, and swelling we feel and see in an inflamed area. These immune cells can also release
additional molecules, which serve to recruit more immune cells, and also increase the sensitivity
of surrounding nerves, thereby intensifying the pain we feel when that area is touched.
This pain keeps us mindful of the affected area, leading us to protect it from further damage,
which is useful from an evolutionary perspective, but is nevertheless unpleasant to experience.
While inflammation is necessary to respond to normal injuries and infections,
its effects can often be excessive, causing additional damage to healthy tissue,
and substantial levels of pain. In addition, the prostaglandin PGE2 can increase our body
temperature, causing a fever. In order to limit harmful and painful levels of inflammation,
we can block, or inhibit COX enzymes with NSAIDs to stop the production of prostaglandins.
Though there are eight structural classes of NSAIDs in total, all of them function to reduce
fever, inflammation, and pain by binding the active site of cyclooxygenase enzymes
and blocking the conversion of arachidonic acid to inflammation-inducing prostaglandins.
Most NSAIDs are organic acids with good “drug properties”, so to speak. They are
readily absorbed in the stomach, distributed through the body, and removed in the urine.
Their chemical properties also lead them to accumulate at the site of inflammation where
the pH is lower, thus enhancing their efficacy. These drugs also share some common side effects.
Most commonly, prolonged NSAID use causes gastric bleeding and ulcers due to the persistent
inhibition of COX-1 and the subsequent disruption of the mucosal lining of the gut. In the United
States, this practice leads to an estimated 100,000 hospitalizations and somewhere between
3,000 and 16,000 deaths annually. NSAIDs can also reduce blood flow to the kidneys, resulting in
possible kidney failure after prolonged use, and they are associated with cardiac risks as well.
So with that, we’ve covered some basics regarding what NSAIDs are,
and how they work. These are characteristics that are shared by all eight structural types of
NSAIDs. Over the next few tutorials, we will discuss common examples from
some of these types so that we can understand what makes them unique,
and why we might select one in particular over the many other drugs to choose from.