Aspirin: how to be a molecular superhero

I saw an article in the Telegraph last week about the recommendations of some experts that everybody over the age of 45 takes aspirin regularly, as the benefits now apparently outweigh the side effects. This made me think that perhaps it is time I had a look at the namesake of this blog, and truly one of the most interesting drugs I’ve ever come across, aspirin.
Aspirin has long been known as 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 before long-haul flights can reduce the risk of deep vein thrombosis. It has been shown to reduce fever. And now, on top of this, trials suggest that it can 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 the superhero it is. But honestly, how can one drug do all this? I’m tired just thinking about trying to do that much in one day.
First let’s take a look at the most well-established use, killing pain. Aspirin is actually an NSAID, which we know from my previous post means that it works by blocking the action of a COX enzyme. However, it is slightly different from ibuprofen and friends, because it is what is known as an irreversible inhibitor, it attaches a chemical group (COCH3, if you’re into that sort of thing) to the enzyme, which means that even once the aspirin has gone, having been broken down and excreted (or because it’s rushed off to save a child from a burning building in true superhero fashion), the enzyme still doesn’t work.
This is in comparison with something like ibuprofen or naproxen, which blocks the action of COX whilst it is bound to it, but will let COX work again once it’s gone. Of course this doesn’t have the effect of blocking pain forever and ever, because the body can make new COX enzymes, but it does make aspirin quite an effective painkiller.
The fact that aspirin is an irreversible inhibitor of COX is also the reason that it can be helpful in preventing heart attacks, particularly if someone is already suffering from coronary heart disease. In the previous post on NSAIDs I explained that what COX enzymes do is act as the catalyst for the production of prostaglandins. We saw how this blocking this production of prostaglandins could limit pain, and also how it could cause some negative side effects. What I didn’t mention though, was that in the case of aspirin there are some positive side effects as well.
One positive side effect is the decrease in production of a prostaglandin known to the masses as thromboxane A2, which plays an important role in the aggregation of platelets in the blood. Sometimes, this is a really handy thing, if your platelets didn’t occasionally aggregate together then you’d pretty much 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. Therefore, in this case, taking aspirin can help to prevent the formation of these blockages. Pretty amazing, really!
It’s worth mentioning at this point that although the Telegraph article reports that scientists are recommending that everyone over-45 takes aspirin daily, it hasn’t actually yet been proven whether aspirin helps to prevent heart attacks and strokes in people who do not already have coronary heart disease, so the recommendation might be a bit pre-emptive, particularly bearing in mind the side effects that NSAIDs can have, most particularly on the stomach lining.
So finally, what of the most recent claims that aspirin can help to prevent bowel cancer in high-risk patients? How does it do THAT? Freeze ray? Well actually, it’s the whole COX-2 thing again. COX-2 is basically the evil nemesis of Super Aspirin. And COX-2 is reported to be over-produced in adenomas, which are usually the starting point for the development of tumours in bowel cancer. Unfortunately for this post, 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. The idea behind aspirin then is that it will block the action of COX-2, and thus prevent the growth of adenomas.
Now I’m aware that this has become a monster long post, probably because aspirin is just too much of a multi-tasker to really be tackled in one go. What I shall do is come back to it another day, it is the blog’s namesake after all and deserves more than one post. Hopefully some of the above made some sense. The key thing to remember from the pile of information above is that whilst aspirin is a super-duper drug, it does also have side effects so it’s advisable not to start popping tablets like Smarties until you’ve check with your Doctor whether that’s a good plan.
I hope you enjoyed aspirin, as with all my posts, please please let me know if anything is unclear to you or appears inaccurate, confusing or downright wrong. I’m extremely receptive to feedback, and I’d love to hear your thoughts or know whether this post has left you with further questions. I’d also love to know if there are any particular drugs you’d be interested in understanding, or indeed anything else you’d like to see me blogging about. I’m always up for a bit of research.

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One thought on “Aspirin: how to be a molecular superhero

  1. I'm int my 2nd year MSc Medicinal Chemistry with OU and S807 is all about pain and inflammation so Aspirin is key. In my blog http://crabsalloverhealth.blogspot.com/2011/10/first-randomised-trial-specifically-for.html John Burns suggests aspirin inhibits cancer by driving programmed cell death (apoptosis) 'making faulty cells fall on their sword'. http://youtu.be/cIJpphg0BR0 – watch from 8mins 20s. Unlike stone-age man, modern man lacks salicylates, which used to be eaten by hunter gatherers from plants growing in the wild.

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