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April 9, 2013 at 8:00 AMComments: 1 Faves: 0

For That Pain in Your Neck

By Lydia from SLN More Blogs by This AuthorFrom the Science Bits in a World of Bytes Blog Series

It seems that no commercial break is complete without drug ads. Everything from migraines to gouty toes has some sort of solution in a pill or bottle. I count myself blessed not to need most of the products advertised. There comes a time, however, when I could use basic pain relief. All the pain relievers do battle, claiming they are the best at helping you. I am curious about the claims and want to see if there’s any truth to them.

Aspirin, sold under the brand names Anacin, Bayer, Bufferin, and Ecotrin, has the active ingredient acetylsalicylic acid. Its half-life in blood is 13 to 19 minutes, while the half life for a prinicipal derivative, salicylate, is 3.5 to 4.5 hours. In ancient Greece, powder from willow trees and spirea was used to treat headaches. The use of such plants continued throughout the Middle Ages until the 1800s, when organic chemistry started to take off, and people became interested in isolating willow bark’s active compound. By 1838, the potent component of willow bark, salicylic acid, had been isolated. The use grew but was limited by the irritation of the digestive tract the acid caused. In the mid- to late-1800s, an acetyl group was attached to the acid, rendering it safer.


John Vane is credited with explaining the mechanism of aspirin activity. It works by inhibiting enzymes called cyclooxygenases (COX). In one variety, COX-2, aspirin acetylates (adds an acetyl group) to part of the enzyme. This keeps the enzyme from producing prostaglandins, which promote inflammation, and thromboxanes, which promote clotting. Instead, the modified COX produces lipoxins, which are anti-inflammatory. Aspirin reduces inflammation also by producing NO radicals. Because it inhibits clotting, take care when taking aspirin so that excessive bleeding does not occur.

Acetaminophen, sold under brand names Excedrin and Tylenol, is another popular pain reliever. Its active ingredient is paracetamol, which has a half life of 1 to 3 hours. Paracetamol resulted from the biological conversion of another molecule to a form better used by the body with fewer adverse side effects. It was first marketed in 1953 with some features touted as making it better than aspirin. Paracetamol did not irritate the stomach, so it was safe for people with ulcers.


Paracetamol works by inhibition of the COX complexes and is selective especially for COX-2, so paracetamol does not affect clotting. Paracetamol is metabolized to a molecule called AM404 , which nearly the same except for a long carbon chain. AM404 inhibits the reuptake of anandamide (do you see the similarities in structure?), a molecule which desensitizes TRPV1, the main pain receptor of the body. Paracetamol has limited peripheral anti-inflammatory properties, so it is not considered an NSAID (non-steroidal anti-inflammatory drug).

The primary metabolism of paracetamol occurs in the liver. There are three main pathways. In the first pathway, a glucuronic acid molecule is attached to the molecule. In the second one, a group containing a sulfur atom is attached. In the third one, the nitrogen atom loses its hydrogen, and the molecule is rearranged to one called “NAPQI,” which undergoes further reaction. The first two pathways account for 60 to 80 of the metabolism of paracetamol, while the third accounts for less than 15 percent. The pathways produce harmless byproducts. However, the NAPQI produced by the third pathway, especially in large amounts, taxes the liver, making it more suspect to oxidative damage; alcohol increases susceptibility of NAPQI poisoning. If there is any question about the current health of the liver, take paracetamol with caution if at all.

My favorite OTC pain reliever is ibuprofen, sold under the names Advil, Nuprin, or Motrin. The name comes from the molecule’s name, iso-butyl-propanoic-phenolic acid. It is classified as an NSAID.  The serum half-life of ibuprofen is 1.8 to 2.0 hours, and by 24 hours, it is basically gone from the body. The molecule was derived from propionic acid by the Boots group and patented in 1961. It was first available by prescription only, but good results on post-approval studies resulted in over-the-counter availability.


Like other pain relievers, ibuprofen works by inhibiting the COX. Like aspirin, it is non-selective, inhibiting both COX-1 and COX-2. The inhibition of COX-1 is responsible for the havoc ibuprofen can wreak on the digestive system.  Other negative effects, especially with chronic usage, include an increased risk of kidney cancer, increase in blood pressure, miscarriage, and photosensitivity. The molecule has been found to be useful in treatment of Alzheimer disease and low blood pressure. In addition, there are tentative findings that low doses of ibuprofen can protect against Parkinson’s. It is stable in solution and has been used as adult acne medication in Japan.


Naproxen is sold under the name Aleve. It has a half-life of 12 to 17 hours. It is a relatively new pain reliever; it was first marketed under prescription in 1976. It is available by prescription only in most of the world. Like other NSAIDS, it is used to reduce pain, inflammation, and fever. It works, again, by inhibition of the COX enzymes. Of all the NSAIDS, it is the one that has the lowest risk of cardiovascular events. It can irritate the digestive tract, causing ulcers and bleeding.

Pain is useful; it indicates that something is wrong. However, it can make us unhappy or, in the case of chronic pain, miserable and unwilling to do anything. Pain relievers help us get going when we need to keep a schedule no matter what. They work in a similar way, although the COX inhibition from aspirin, unlike that of the others, is irreversible. There are risks with large doses, but don’t be afraid to take a pill or two should the occasion call for it.


Aubuchon, Vaughn. "Pain Killers Comparison Chart." Vaughn's Summaries. N.p., 04 Mar 2013. Web. 14 Mar 2013.

"Ibuprofen Tablets USP, 600 mg." Perrigo, n.d. Web. 14 Mar 2013.

"Naproxen Official FDA Information." Drug Information Online., 14 Mar 2013. Web. 14 Mar 2013.

"Pharmaceutical Information-Aspirin." RxMed. N.p., 19 Oct 2002. Web. 14 Mar 2013.

"Paracetamol Pharmokinetics." University of Lausanne, 14 Mar 2013. Web. 14 Mar 2013.

Vane, J.R., and R.M. Botting. "The Mechanism of Action of Aspirin." Thrombosis Research. 110. (2003): 255-258. Web. 14 Mar. 2013.

Wikipedia and PubChem Sketcher 2.4

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Next:The ABCs of Chemistry: Part 3Previously:The ABCs of Chemistry: Part 1

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1 Comment

  • Aleve works best, but Ibuprofen is second when Aleve does not work on my worst pain.

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