Complete question: How do painkillers such as Advil and Tylenol work? Do they neutralize specific neurons under specific conditions? And why do they also reduce fever? And another question: I noticed on a box of Advil (but may have misinterpreted) that it says that taking this drug should be accompanied by three glasses of an alcoholic beverage. Why is that?
As always with such questions, I will begin with a disclosure: the writers on "Ask our Experts" are not medical doctors, and for this reason all answers relate only to the scientific aspects of the question (in this case the mechanism of action of painkillers). For this reason, one should not seek in this website any medical advice regarding the use of one drug over another or regarding any potential side effect. Such questions should be referred to your general practitioner or to the many medical forums available on the web.
Advil and Tylenol are brand names for the generic drugs ibuprofen and acetaminophen (also known as paracetamol), respectively. Both are painkillers (analgesics) that belong to the class of drugs known as NSAIDs – non-steroidal anti-inflammatory drugs
Left: chemical formula for ibuprofen (Advil); Right: chemical formula for acetaminophen (Tylenol). Adopted from Wikipedia.
These drugs act by inhibiting the production of prostaglandins in our body. The following flowchart depicts the biochemical pathway in which prostaglandins are synthesized in our body, and the site of inhibitory action of Advil and Tylenol.
Phospholipids are a main constituent of most biological membranes and are an important component of the cell wall. One of the biochemical breakdown products of phospholipids is arachidonic acid, which participates in intracellular signaling (acts as a secondary messenger in different signaling pathways). On a side note I will mention that steroids interfere with this process by inhibiting the enzyme that is responsible for the breakdown of phospholipids.
Arachidonic acid can be further broken down by additional enzymes, including cyclooxygenase 1 and cyclooxygenase 2 (COX1 and COX2). The products of the COX enzymes are prostaglandins, a family of lipids that play a key role in many processes in our body. The number of processes in which prostaglandins participate is far beyond the scope of my answer, so I will only mention that they take part in inflammation, pain sensation and the rise in fever associated with the inflammatory response. Therefore, inhibition of prostaglandin production can reduce pain and fever.
As mentioned, two enzymes are responsible for prostaglandin production: COX1 and COX2. The former is active most of the time, while the latter is active mostly during inflammation. Most NSAIDS, among them Advil and Tylenol, are non-selective and suppress the action of both cyclooxygenases. In recent years several drugs have been introduced that specifically inhibit COX2. One of the major advantages of these more specific drugs is reduced risk for stomach ulceration, a possible side effect in prolonged use of NSAIDs. Nevertheless, some of the new drugs have been associated with cardiovascular risks, to the extent that they have been removed from the market.
Regarding the second part of your question – had this been true the sales of Advil would have greatly increased, especially on weekends… Long lines would be observed outside your local pharmacy with people on a mission to purchase some Advil as a pretext for alcohol consumption. The truth is in fact the exact opposite: when taking medicine in general, and particularly drugs that undergo metabolism in the liver (as in the case of NSAIDs), it is highly recommended to refrain from drinking alcohol, due to possible complications. Additionally, assuming that the person taking Advil is already sick with fever and inflammation, drinking alcoholic beverages can further hamper his judgment and demeanor, certainly an undesirable effect.