The NSAID side effects: tummy aches, kidneys and cake

I promised I’d come back to the non-steroidal anti-inflammatory drugs (NSAIDs, oh how glad I am I only need to type that for you once each post!) and deal with some extra niggly little issues… like side effects. Before I get to that, however, it was brought to my attention that I misrepresented a few points in the original post in my attempts to simplify the science (thanks to biochembelle for picking me up on this), so I have slightly amended that post to be hopefully more accurate! Don’t panic, however, the essentials are correct, I just failed to proofread carefully enough (big shame on me as an ex-scientific publisher!), which lead to a couple of oversimplifications.
So, back to the scary side effects. Side effects are an unfortunate problem with almost every drug available. Probably you’ve gathered this from the lovely pages of warnings nestled into each packet that you buy. The problem with drugs is that the body is rarely straightforward (you might already have picked up on that one!) so whilst you might be able to inhibit an enzyme and stop something bad happening, there’s always a risk that you might stop something good happening too. In the case of the NSAIDs, I’m going to use the example of ibuprofen; partly because it is currently working its lovely painkilling power on my uber headache, and partly because it’s a well-known and handy example.  I discussed before how ibuprofen, as an NSAID, stops pain by inhibiting the COX-2 enzyme, however if you remember, I did rather skim over the other COX enzyme, COX-1.  Now is the time to correct that.
Further to my earlier explanation then, ibuprofen is what is known as a ‘traditional NSAID’ and this means that it does inhibit both COX-1 and COX-2, even though it’s the inhibition of COX-2 that is useful in terms of stopping inflammatory pain. There are actually some newer NSAIDs that have been developed to specifically inhibit COX-1 and thus limit some of the side effects (a couple of examples of these are celecoxib and rofecoxib), but most over-the-counter NSAIDs do inhibit both.
The most common side effect of traditional NSAIDs like ibuprofen is gastrointestinal disturbance, and this is largely caused by inhibition of COX-1. Hopefully you remember (if not, you’re almost certainly not the only one, to be honest) that COX enzymes catalyse the production of prostaglandins.  Prostaglandins in the stomach have an important role in slowing down the secretion of stomach acid and increasing the production of protective mucus. So, inhibiting COX-1 in the cells lining the stomach leads to fewer prostaglandins, which in turn means that less mucus is produced to line the stomach and more acid is secreted. And, as anyone who has ever squirted lemon juice in their eye will know, acid is usually a rather painful thing to have hanging around. Of course, your stomach is supposed to be acidic, but the amount of acid is usually extremely carefully regulated, specifically to stop any damage being done to the lining of the stomach.  Inhibiting COX-1 upsets this balance and, in extreme cases, can lead to damage and bleeding. In most cases it would just lead to a tummy ache, not hugely serious but still not what you’re after, really, particularly if you just went to the trouble of taking a painkiller. This is the reason that you’re told to try and eat before you take an ibuprofen tablet, because your stomach is meant to be more acidic when there’s cake in there (or any other type of food actually, it’s just usually cake in my case) and so there’s less risk of any damage to the lining of your stomach.
I don’t want everyone to reads this post and start panicking that ibuprofen will give you gastrointestinal bleeds, unless you already have something dodgy going on in there, it won’t. If it was that dangerous they wouldn’t sell it to you over the counter. Equally, I am in no way suggesting that you should always eat cake with your painkillers (although, now I mention it, it’s not the worst idea ever, Dragon’s Den here I come… cakeprofen!). I merely share this knowledge because I genuinely believe that it’s best to understand both the good and bad things that drugs do in your body, because if you understand them you can work with them. Plus, and more importantly to a certain extent, I think it’s really flipping interesting. That could just be me though, as I’ve said before, massive geek over here.  
So with the most common side effect covered, I can just briefly explain another interesting, but much less common, side effect. Kidney problems can be caused by blocking the production of prostaglandins. In this case the prostaglandins increase blood flow through the kidney and help with the excretion of sodium into urine, both of which are rather crucial. Very prolonged long-term consumption of NSAIDs can lead to serious kidney damage due to the prolonged inhibition of these processes.  Again, this isn’t at all likely to happen to any of you, it’s just fun to know this stuff. And if they ever start introducing biochemistry or pharmacology rounds into pub quizzes you’ll be triumphant. Actually if this ever does happen to anyone, please call me, I’ve always wanted to be good at even one pub quiz round! :-p
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 you thoughts. 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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