A brief look at the application, history, and mechanism of four over-the-counter drugs.

Aches, pains, fevers, coughs, and congestion are just a pill away from remedied. You don’t even need a doctor’s prescription. During the twentieth century modern chemistry allowed over-the-counter drugs to progress from snake oil to FDA certified, scientifically proven medicine. With low prices and availability in any ubiquitous pharmacy, non-prescribed drugs have become a staple of modern living.

I think it’s a good thing. These medications help combat the symptoms of chronic diseases and make life livable for millions of people. If it weren’t for antihistamine drugs, I wouldn’t be able to go outside from May to July because my seasonal allergies get so bad. But it’s very easy to take these medications for granted. We know them by their brand or generic name, we know their doses and applications, but for many of us the active ingredient may as well be a magic potion.

I’m going to list four common over-the-counter drugs, their application, history, and how they work.  This article by no means constitutes medical advice. Consult a physician before starting any medication. Always follow your physician’s orders or the instructions on the medication. Many of these drugs have uses as prescribed drugs, I generally won’t be covering those facets. They should only be used as directed for the specific symptoms. These drugs, though very helpful, can have deleterious side effects if improperly administered.

Acetaminophen:

Acetaminophen is the most commonly used antipyretic (antifever) and analgesic (pain reliever) in both the United States and Europe. Its typical dosage is 500-1000mg, taken orally, every 8 hours as needed. It is known by a number of names, most commonly Paracetamol, Tylenol, and Panadol, but there are dozens of brands.

The medications use as an antipyretic was discovered in 1866, but this version of the drug, Acetanilide, was toxic in low doses. It was used clinically in 1899 as a new derivative: phenacetin. In 1947 David Lester and Leon Greenberg discovered paracetamol, a metabolite of acetanilide and phenacetin. That means it is the end or an intermediate product of the metabolism of acetanilide and phenacetin. Paracetamol does not have the harmful side effects as its precursors, making it a safe and effective drug. Introduced to the American market in 1950 as Acetaminophen and British market in 1956, paracetamol has become an essential drug to modern medicine.

The mechanisms of paracetamol’s antipyretic properties are not completely understood. Fevers start when immune cells called phagocytic leukocytes release molecules called endogenous pyrogens. These endogenous pyrogens travel to the brain and tell the hypothalamus to start heating the body up. Acetaminophen crosses the Blood Brain Barrier (BBB) and interrupts this process by keeping the hypothalamus from releasing fever activating hormones.

Acetylsalicylic Acid:

Acetylsalicylic Acid, or Aspirin as it is commonly known, is one of the oldest actually useful medications. Hippocrates, of Hippocratic Oath fame, is recorded having used salicylic acid in the form of willow bark tea as a pain reliever for pregnant women. It is a non-steroidal analgesic and anti-inflammatory drug; typical dosage is 300-600mg every 6 hours. Aspirin is also commonly prescribed as a blood thinner by doctors for patients at risk of heart disease.

The uses of salicylic acid is first described in ancient texts dating back to ancient Egypt. The modern version of the drug, acetylsalicylic acid was synthesized in 1853 by chemist Charles Fredric Gerhardt. In its time it was considered a wonder drug and paved the way for other modern medications. The medication got its name when the company Bayer started producing it in 1899 as Aspirin. They lost the rights to the name in 1921 and now it has become the common name of acetylsalicylic acid. Since 1853 Aspirin has become one of the most widely used drugs in human history.

Acetylsalicylic acid has two main methods of action. First it inhibits enzymes called cyclooxygenase, which in turn blocks inflammation. It also interrupts local pain enzymes from communicating with the brain, this is the same pathway that acetaminophen interrupts. Another interesting side effect of continued acetylsalicylic acid use is the inhibition of thromboxanes, which causes inhibition of platelet formation. This is why in low doses Aspirin is commonly used as a blood thinner to prevent risks from blood clotting.

Ibuprofen:

Ibuprofen is another analgesic and antipyretic that is safe in proper dosage and used ubiquitously. Also known as Brofen, and subsequently Advil and Motrin, it is used for many diseases with chronic pain and inflammation. Ibuprofen is also very helpful in lessening the discomfort of menstrual cramps. The typical dosage is 400-800mg taken 4 times a day or as needed.

Ibuprofen was first discovered by Stewart Adams in 1961. The Boots Company was first to bring the drug to the market as competition for Aspirin. Since its discovery ibuprofen has become an essential medication according to the WHO and is a staple of modern medicine.

Much like Aspirin, Ibuprofen works to inhibit cyclooxygenases.  The interruption of the cyclooxygenase chain disrupts pain sensation as well as fever and inflammation. Making ibuprofen a commonly used drug for inflammatory diseases like arthritis.

Diphenhydramine:

Diphenhydramine is a personal favorite of mine; it is an antihistamine used widely to combat allergic reactions. It is taken to help with itchiness, sneezing, flushing, and swelling. Side effects include drowsiness and dizziness. I don’t drive if I’ve taken a dose, especially if I’ve had any alcoholic beverages. Typical dosage is around 25-50 mg every 6 hours, or as needed. Its is commonly sold under the brand name Benadryl, owned by Johnson and Johnson.

Diphenhydramine was discovered in 1943 by George Rieveschi and was the first antihistamine drug. Since then it has become one of the most common antihistamine and anti-allergy drugs.

Diphenhydramine works by inhibiting Histamine1(H1) receptors. H1 is a receptor on our cells that is activated by histamine. Histamines are compounds released by the body in response to injury or an immune attack. H1 receptors can be found all over the body in smooth muscle, veins, arteries, the intestines, and many other locations. Once activated they cause the response of flushing, itchiness, swelling, and other symptoms associated with allergies. The overreaction of histamine response seen with allergic reaction can be mediated with antihistamine drugs.

It is important to understand how the technology we use works, even at an elementary level. We have reached advances in medical technology more akin to miracles and alchemy than the palliative care of previous centuries. I hope I’ve helped make the process of these medications a little more digestible. Feel free to comment if you have questions or comments. I’d like to do more of these short blurbs describing other drugs.

References:

Karch, A.M. (2017). Focus on Nursing Pharmacology. Philadelphia: Wolters Kluwer.

Bushra, R., Aslam, N. (2010). An Overview of Clinical Pharmacology of Ibuprofen. Oman Medical Journal.

Sicari, V., Zabbo, C.P. (2019). Diphenhydramine. Florida: National Center For Biotechnology Information.

Meredith, T.J., Goulding, R. (1980). Paracetamol. London: Post-Graduate Medical Journal.

Various Ancient Authors (1st century CE) De Materia Medica, Rome.

Kwok C.S., Loke, Y.K. (2010) Critical Overview on the Benefits and Harms of Aspirin, Pharmaceuticals-Open Access Journal.