How Drugs Work: Aspirin

Aspirin has a reputation as something of a wonder drug. It was originally developed as a painkiller, but in the past decade it emerged that it can help to prevent heart attacks and strokes in patients diagnosed with coronary heart disease. It has been suggested that taking it can reduce the recurrence of deep vein thrombosis. It has been shown to reduce fever. And, on top of this, trials suggest that it might help to prevent colorectal cancer. Yep, that’s right, if aspirin wore pants, it truly would wear them over the top of its leggings, like an all-singing, all-dancing molecular superhero. But honestly, how can one drug do all this? How does it do any of it? I’m tired just thinking about trying to do that much in one day, as I sit here typing in my pyjamas. Aspirin is capable of so much, because it has a truly amazing nemesis…

Aspirin: here to save the day!

Aspirin: here to save the day!
Image credit.

Aspirin as a painkiller

Aspirin is classed as a non-steroidal anti-inflammatory drug (NSAID), it reduces pain by reducing inflammation. Inflammation is a process your body uses to heal wounds, patch up problems, repair damage and fight infection. Amongst other things, inflammation causes pain. This seems a bit counter-productive, why should it hurt to heal yourself? The pain is there to make sure that you’re aware that something is wrong; it’s an alarm system, a siren flashing CODE RED to your brain to make sure you’re aware of the damage, and the need to protect the painful area while it heals. Basically the pain is there to make sure you don’t ram your injured body part into a wall, or anything daft like that.

In order to react to damage, your cells have an inflammatory response team, who come complete with excellent theme music, like the A team. This inflammatory team includes an enzyme called cyclo-oxygenase-2 (COX-2). COX-2 has a job; its job is to convert arachidonic acid into prostaglandin H2. This may not sound like a dream job to you, but it’s an important role, and COX-2 sees it as something of a calling. Once COX-2 has converted arachidonic acid into prostaglandin H2, the prostaglandin then goes on to be changed into prostanoids, which are key players in mediating the inflammatory response: once the prostanoids are on the job, inflammation is happening.

Unless, that is, aspirin is hanging around. Aspirin targets the COX-2 enzyme, and whenever it finds COX-2 it attaches a chemical COCH3 group to it. With the chemical group blocking it, COX-2 is unable to fulfil its calling, and arachidonic acid remains unchanged, reducing the number of prostanoids and thus reducing the inflammatory response. Aspirin is such a bad-ass NSAID that even once it has left the area, presumably to save a child from a burning building or something equally molecular superhero-like, the COX-2 enzyme that has been blocked cannot function. Your body is required to make new COX-2 enzymes from scratch before it can start producing prostanoids to get on with the inflaming again. While the majority of COX-2 enzymes in the area are blocked, therefore, the inflammation and pain in the area is decreased.

Aspirin in coronary heart disease

Prostaglandins are not involved in inflammation alone. One particular prostaglandin, thromboxane A2, plays an important role in the aggregation of platelets in the blood. Sometimes, this is a really handy thing, if your platelets didn’t aggregate in certain circumstances then you’d never stop bleeding once you cut yourself, and it’s pretty evident that that would suck. However, if you suffer from coronary heart disease, then platelet aggregation can lead to blockages in your arteries, and these blockages can lead to heart attacks or strokes. If aspirin blocks COX-2 in this situation, less thromboxane A2 is produced, and the blockages may be reduced.

Aspirin in bowel cancer

So what of the claims that aspirin can help to prevent bowel cancer in high-risk patients? How does it do THAT? Freeze ray? Sadly not, cool as that would be. There are several theories on this, but one of them suggests that it all comes down to COX-2 again. COX-2 is suggested to be over-produced in adenomas, which are usually the starting point for the development of tumours in bowel cancer. Unfortunately, the role of COX-2 in adenomas hasn’t been fully established but it does seem that it has a role in increasing their growth, which is one of the key things that you want adenomas NOT to do, really, because that’s when they start to turn cancerous. In this situation, aspirin once again blocks the action of COX-2, and in theory prevents the growth of adenomas.

So that’s it; the basics of how aspirin became a molecular superhero. Most theories suggest it relies on the brilliance of COX-2 (although this post is by no means exhaustive, and there are other theories, there are pages and pages and pages of studies on aspirin out there, some of which have been linked to in the comments below). COX-2 is the true star of the show, it has such a wide range of roles within the body, and these varying roles allow aspirin to work in a range of different ways. Aspirin is so impressive because it targets such an impressive enzyme. If COX-2 is the evil nemesis to aspirin’s superhero, then like so many evil villains, it is actually a misunderstood hero.

*Please note, guys, I am not a doctor, I’m just a really nerdy pharmacology enthusiast who likes to know how things work, please don’t start taking aspirin like superhero smarties unless you’ve spoken to your actual doctor. Do feel free to eat actual smarties though.*

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5 thoughts on “How Drugs Work: Aspirin

  1. Aspirin is not just for people with a high risk of bowel cancer. Peter Rothwell from Oxford Uni has shown that daily 72mg Aspirin may help to reduce the risks of getting any cancer, for people over 50.

    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60209-8/abstract

    Cancer Research UK comment on the Rothwell study: http://scienceblog.cancerresearchuk.org/2012/03/21/aspirin-and-cancer-the-picture-becomes-clearer/

    More on Peter Rothwell work on aspirin and cancer on my blog: http://crabsalloverhealth.blogspot.co.uk/search/label/Peter%20Rothwell

    But before anyone takes Aspirin daily, discuss the risks and benefits with your doctor!

  2. Thanks for the links! I’ve updated the post to clarify that some of these above are only theories. and to draw attention to your links.

    Also added my standard I’m not a Dr disclaimer, which I apparently forgot last night!!

    K x

  3. Pingback: How Drugs Work: Aspirin | Science Communication Blog Network

  4. Pingback: The Week in Science (March 25 – 31) | Science Communication Blog Network

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