Paracetamol, in particular, is a slightly tricky NSAID, it’s actually not particularly good at stopping inflammation (so in one sense it’s a fairly rubbish NSAID) but it does have other effects, including lowering body temperature, which is why it is so often taken when you have a fever. There is still some debate in the scientific community about exacty how paracetamol acts to lower fever and kill pain, seeing as it doesn’t appear to inhibit COX as well as the other NSAIDs like ibuprofen. It is known that in the hypothalamus (the part of your brain that contains your internal thermostat), prostaglandins are involved in elevating temperature due to inflammation, usually caused by viral or bacterial infection (you’ll have noticed this if you’ve ever had flu or any flu-like virus), however this sadly doesn’t necessarily mean that paracetamol blocks COX to lower temperature. For such a common drug, paracetamol is suprisingly elusive in terms of understanding how it works! For most of the other well-known NSAIDs, particularly ibuprofen, the above does apply. They do prevent inflammation by blocking COX. So, there you have it. A simple explanation of how NSAIDs can block pain, reduce inflammation and lower body temperature. And a good reason why they are so welcome at many a family gathering. Next time we’ll have a look at what side effects NSAIDs can cause and why this happens.
Ibuprofen must be one of the most commonly taken drugs in the country, and yet most people who take it have no idea how they are working in their bodies to take the pain away. So, I’m going to answer that much-asked question… how does a painkiller kill pain? Well actually the first answer to that is, it depends on which painkillers you take. And because the complete answer is so long, I’m going to attack the question in several blog posts, starting with the basics about paracetamol and its nearest and dearest relations. Ibuprofen is a member of a group of drugs called the non-steroidal anti-inflammatory drugs (it’s a good long name so I’m going to refer to these from now on as the NSAIDs) and these drugs are basically exactly what they say they are, they are drugs that reduce inflammation but they are not steroid-based. As well as reducing inflammation, they also reduce certain types of pain and they can lower body temperature. Other well-known over-the-counter attendees at the NSAID family Christmas include aspirin and naproxen.
If you remember the basic principles of drug action, you’ll remember that drugs act by binding to things. In this case, the NSAIDs act by binding to a protein, specifically an enzyme called cyclo-oxygenase or COX. There are three types of this COX enzyme and they are brilliantly named COX-1, COX-2 and COX-3. For the majority of this post, however, we’re going to pretty much ignore COX-1 and COX-3 (COX-3 is actually a completely useless enzyme in humans) and focus on COX-2. COX-2 is an enzyme (remember that an enzyme is a biological catalyst, it whips around helping to speed up biological reactions) however it isn’t always present in all of your cells. Rather, it is present in some cells of your body constantly (constitutively expressed) and in others it only pops up when your body is experiencing what is known as an inflammatory response. Inflammation is the way in which your body responds to certain harmful stimuli, it involves certain cells releasing chemicals and molecules that cause several things to happen, including swelling, redness, an increase in temperature and pain. If you’ve ever had an insect bite, a nettle sting or an infected cut, you’ll know the signs. We won’t concern ourselves just now with how inflammation causes pain, although that might be the topic of a later blog post, we’ll just accept that COX-2 is produced when this inflammatory response is going on and we’ll take a look at what COX-2 does when it arrives.
So, COX-2, being an enzyme, needs a reaction to speed up, and the biological reaction that COX-2 is involved in is the conversion of chemical called arachidonic acid into something called prostaglandinH2. Prostaglandin H2 is then converted into a number of chemicals known as prostanoids, and prostanoids are amongst the chemicals that are released in the inflammatory response that we just described. Hopefully, then, you can see that if we stopped COX-2 from producing lots of prostaglandin H2, we would stop the production of prostanoids and, therefore, inhibit some of the inflammatory response. This is, in essence, exactly what NSAIDs like ibuprofen do. Of course, it’s not quite as simple as all that (nothing ever is)… not all NSAIDs have exactly the same effects (because they don’t all work in exactly the same way) and some NSAIDs also have some pretty nasty side effects. I’m going to save the side effects for another post but let’s have a brief look at what else NSAIDs can do.