Edit: Thank you very much for the gold! I hope the comments made to this post were as helpful to others as they were to me.
In: Biology
Vast topic- here is a quick attempt-
1- receptors get used to drug. Take some pain medicine- body makes more receptors for that medicine- now you need more pain medicine to fill up those receptors. Feed your puppy- he grows bigger- now you need to feed it more
2- liver- some medication rev up /down the system. Produce or reduce the amount of enzyme. Alcohol is good examples… 1 beer after a long time is a good buzz.. drink it everyday- you don’t event feel it.
Another good example is the overexpression and/or increased activity of drug efflux transporters. These transporters are present on the cell membrane and can export drugs out of the cell, thereby reducing the overall intracellular concentration and reducing the efficacy of the drug.
Alternatively, there may also be increased expression/activity of enzymes such as the CYP450 family which metabolise drugs into a non-active form (if the drug isn’t a pro-drug), similarly reducing the concentration of active drug in the system. The activity and expression of these enzymes can be pre-determined by our very own genetic make-up but also modulated from the things we consume (food, drink, other medication), things we are exposed to (chemicals in cigarette smoke) and even our current state (age, pregnancy).
As for the specificity of drugs which a tolerance is built up towards. These drug efflux transporters and enzymes typically interact with a subset of drugs and it is these drugs which become less effective over time.
I think it just depends on if the cell has a counteracting/balancing mechanism or not.
Generally, signaling molecules like hormones or neurotransmitters have what’s called a negative feedback loop. If the amount is too high, certain mechanisms work on reducing it and vise versa.
So external influencers might force the cell to change some of its structure (e.g reducing the amount of receptors), to accommodate the new change.
Of course the change might be on certain levels that don’t change the outcome, for example anabolic steroids are taken to increase testosterone to levels higher than 10 folds and yet, muscles still respond to that change with no counteraction, while the testes would shrink in an attempt to reduce the high level of testosterone.
Medications can work in a lot of different ways. One type that is prone to building tolerance are drugs that work in the brain by changing the strength of different chemicals. If a drug increases the effect of one chemical, then it works well at first, but the brain often adjusts one area to compensate for another. The brain might get rid of some of the receptors that are used by that chemical if it decides there is too much of it, making the drug less effective. Sometimes that just means the person needs a dose increase, because usually this balances out and you can still end up with more of that brain chemical than you had before, even after the brain tries to compensate for it.
This is also how drug addiction and withdrawal can work. If a drug causes your brain to reduce activity in an important area, then stopping the drug can leave not enough of it. This is really bad if that chemical helped your brain slow down when it needs to, and that’s how withdrawal seizures can sometimes happen.
Other medications work in different ways that don’t cause your body to compensate for them and are less likely to lead to tolerance.
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