This question came about as my wife has just started a course of steroids to treat her Crohn’s Disease. They work amazingly well, amazingly quickly… But they are only a temporary solution as they have a range of significant side effects such as thinning of the bones, insomnia, etc…
Steroids are “old” in medical terms – why haven’t we managed to remove the side effects yet?
In: Chemistry
It’s a good question. Ultimately many medications we use have many different mechanisms in our body and it’s very hard to solely isolate one use case from all the rest. For example baby aspirin is used to help heart disease because it is a platelet inhibitor, but as an NSAID it can also be anti inflammatory for fevers, and analgesic for pain. But take too much of it and it can cause stomach ulcers because it thins the mucus lining of your gut. Also lots of meds are discovered by accident frankly. Warfarin was a rat poison before it was used for blood thinning in afib and heart valve replacements. Nowadays things are getting more narrowed down- chemotherapy in its early form was basically straight up poison for the body whereas now we have things like immunotherapy that specifically target various immune cells in the body.
Edit: it’s the same thing with Crohn’s disease which you mentioned in your post. Steroids work amazingly well and in flares they are still the first line of defense we have. There are immunotherapies and immune modulators that are used in IBD now too. But even that is not a perfect science since they are essentially immune suppressants. Hopefully in the future things continue to advance even more!
Because:
1. Biochemistry is *enormously* complex. Literally *millions* of compounds factor into some of the most basic things living cells do. We literally *don’t know* most of the biochemical reactions inside our bodies. We *barely* know the superficial surface of the really common reactions.
2. Drugs are not LEGOs that you can rebuild whenever and however you like. They have rules for their structures, rules we can’t just willy-nilly ignore. To get a different medicinal effect, you would have to *heavily* change the molecule–which may create all sorts of *new* side effects.
3. The receptor sites that respond to drugs are not like wall sockets or battery ports. Instead, receptor sites are like a dress code. There *are* rules for what is and isn’t allowed in, but the rules allow many variations. Sometimes you can even bend the rules by adding other things.
If drug companies *could* produce a drug with few to no side effects, they would. Because they’d be able to patent it and make a crapton of money, *especially* for something like steroids, where as you say the drugs are old, so a major innovation would be a very big deal.
Dermatologist here, but we use steroids a lot in our practice of medicine. Not ELI5, but for your particular example, we often repurpose already existing compounds or chemicals. And thus though we may use them to obtain a particular effect, it’s inevitable that they will also do other things. Our bodies are complex contraptions that we don’t fully understand and are learning bits about how they work all the time.
For example, the “steroids” your wife got for her Crohn’s are in a group of steroids we call glucocorticoids. These are synthetic steroid hormones that we have created to mimic the body’s naturally produced glucocorticoids. We use them because normally glucocorticoids are used in the normal feedback of the immune system to essentially turn down inflammation, though they also are used in tons of other bodily processes, including bone metabolism (hence osteoporosis), metabolism (they play an integral role in moving sugars, fats, and proteins into different compartments of the body), and the brain (they act in multiple ways as part of the stress response “flight or flight” signalers, to help enhance memory formation, etc.) In order to shut down your wife’s abnormal inflammatory response in her colon, we flood her system with glucocorticoids in hopes to prevent her Crohn’s from destroying her GI tract.
It’s kind of like commandeering the water pipes in a grocery store. They help supply the water that mists vegetables in the produce department, make the ice to keep the fish cold, supply water fountains for drinking, etc. They’re a natural part of the building and have an important role to play, but when there’s a fire, we open up all the taps and let the building flood to prevent the building from burning down. Yes, the floor will be ruined, and the vegetables probably spoiled, but it’s better than a 100% loss.
There are more and more targeted therapies coming out that have less side effects, like in dermatology we have biologics like IL-17, IL-22, IL-23, IL-4 inhibitors, to help treat other autoimmune diseases like eczema and psoriasis. These act further downstream in the immune pathways to hopefully cause more targeted immunosuppression. This would be like only opening up the pipes that supply the sprinklers to only the part of the building that is on fire, instead of all the sprinklers in the entire building. For Crohn’s, gastroenterologists use many of the same medications.
Biology is absurdly, mind-bogglingly complex. It almost has to be, given that every biological system that exists today cobbled itself together out of previous pieces, so to speak. Almost every system in your body is controlled by several different signalling pathways, and almost every signalling pathway in your body helps control several different systems. If you make a minor change to one particular pathway with a drug/peptide/biologic/etc, it’s almost certainly going to have effects on other systems. At its heart, biology is based on chemical reactions, and sometimes we can’t make those reactions happen the way we need them to.
The body sometimes cannot deal with an issue due to some irregularity. If you take a medicine to compensate, your body now has to deal with this new substance. It needs to clean it out of your stomach and digestive track, it needs to clean it out of your blood, and it needs to ensure that it hasn’t stuck around in any of your muscles, bones, skin, or fat.
The body going through this process is what leads to a lot of negative side effects. The reason for thinning bones is often because calcium is needed to properly neutralize and remove the drugs from the patients system, and the largest stores.of calcium are in the bones. So the body starts stripping calcium from your bones, combining it chemically with the drug chemicals, and then pees it out.
There are also side effects thst are caused by the drug interacting with more than just the parts you want it to. Take antibiotics for example. Antibiotics kill almost all microscopic organisms good or bad for us. Taking oral antibiotics can often have a positive effect on an infection, as the body will take these antibiotics to the site of infection and use them to heal. However the body will not be able to do with with 100% of the antibiotics in the pill you consume, so some of it will make its way into your digestion and start killing everything in your gut. As a result, most people who take antibiotics orally suffer from the side effect of diarrhea as the microscopic organisms that help them digest food are damaged, dead, or trying to recover from the antibiotics.
At best you can mitigate side effects, but if something will interact with one thing, it’ll interact with something else and humans are at *least* three or more things put together. So like you need oxygen to survive, but then oxygen is also theoretically the cause of aging (free radicals, etc).
The trick with medication and really anything else is moderation. Find the amount that does what you want it to do with minimal side effects.
The human body is an incredibly complex machinery of chemical reactions. Medicines act by changing or affecting that machinery slightly to get the desired effect.
But the machinery is so complex that it is impossible to make a change that has only a single effect. There will always be other effects.
When those other effects are undesired, noticeable, problematic or risky, we call them side effects or adverse reactions.
The biochemistry of the human body is beyond enormously complex. Worse yet, different people may have slightly different biochemical pathways for a given reaction. A friend doesn’t respond at all to opiates, another is hypersensitive to them. Ditto for lots of other reactions.
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