why you DON'T develop resistance to some medications?

Submitted by sadra-the-legend t3_10te3a8 in askscience

I know people who take drugs for HTN for years or Anti-depressants and etc.

so why don't you develop resistance to them? or why do some side effects go away but the main effect of the drugs persists without increasing the dose?

(i think side effects are because of the same receptors but in a different part of the body. (also I know all the drugs don't work by blocking a receptor))

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Bad_DNA t1_j774otc wrote

Often, the meds are either interacting directly with the body systems as a substitute for missing/tiny titers of the natural active component, or act as an antagonist for the same, so metering/shutting down the target system. This isn't quite the same as other systems that can develop tolerances (thereby requiring higher doses for the same perceived effect). Honestly, we'd have to take this on a case-by-case basis as no blanket statement is correct. Nor does this function in a natural selection format like antibiotics with bacteria that either evolve of die, where plasmids xfered via sex confer resistance for survivors.

There are plenty of other metabolic considerations. Some drugs are useless in their taken form, and only modifications/metabolism in the gut biome or liver or elsewhere generate the active physiological daughter products.

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Lingering_Louse t1_j79r2b6 wrote

I’m a doctor. Medications act on enzymes or receptors. These medications can activate receptors, de-activate them or turn on/off chemical pathways.

The question becomes which pathways, when activated/inactivated cause I disruption of homeostasis (the bodies ability to regulate itself). If a drug turns on/off a receptor and the body senses that as a disruption of homeostasis, then the cell will make more receptors so there is more activation or stop production of those receptors. These are the medications that cause tolerance.

Some medications don’t affect a pathway where upregulation or down regulation by receptor expression is possible, these are the drugs that do not cause tolerance.

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tyler1128 t1_j795cvh wrote

We do know that SSRIs cause a withdrawal of sorts if stopped abruptly, this implies some sort of adaptation in the brain's serotonin system, or some other downstream effect. To really answer why you don't generally grow resistant to SSRIs would require to understand exactly why SSRIs work for depression, and we don't yet. One hypothesis is not that the additional serotonin is the direct way they work, but that the presence of more serotonin downregulates certain serotonin receptors and that downregulation is ultimately what gives it therapeutic benefit.

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