questions about drug tolerance

[gib65]

Hello,

I understand that scienceforums.net is not about giving medical advice, but I have some questions about how drug tolerance works and I'm wondering if anyone knows about a good source that will answer my questions.

Here's some example questions:

1) Can I expect that the time it takes to get over tolerance is relatively equal to the time it takes to become tolerant? So let's say it takes 4 days to become tolerant to a drug at a specific dose. Would it then take 4 days to undo the tolerance if I abstain from the drug for those 4 days?

2) Would tolerance buildup occur at the same rate if I consumed a certain dosage of a drug once per day vs. consuming half that dose twice a day. For example, suppose I consistently had 2 cups of coffee every morning, one immediately after the other. Compare that to having 1 cup every morning and another cup in  the afternoon. Would I become tolerant to caffeine at the same rate in both cases? Or would it happen quicker in one case or the other?

3) Can I avoid tolerance buildup by taking a drug at a low enough dose each day?

4) Does tolerance buildup begin to occur after just one consumption, or do I have to consume a drug several times in a row before tolerance begins to occur? If so, how many times in a row?

If anyone can answer these questions, great! But if it is inappropriate to answer them hear, I would appreciate being directed to another place where I can get my questions answered. Thank you.

[guidoLamoto]

We have to determine what you mean by "tolerance." For instance, many drugs are metabolized by certain enzyme systems, often determined by single genes, that controls how quickly a drug builds up in the body to achieve its therapeutic level (or toxic level) and how quickly it's removed from  the body. There are also genes controlling how well a specific drug will work or if it will work at all. ..Then there's the phenomenon of tachyphylaxis-- some drugs require periodically increasing doses to achieve the same effect as the previous, lower dose. Many of those drugs also show the phenomenon of a withdrawal syndrome when suddenly discontinued.

In general, the time required to achieve a given drug level is also the time required to remove the drug from the system upon discontinuation. Return to the baseline level of "tolerance" may take longer, given that the enzyme & receptor systems involved often show "recruitment" and need time to return to baseline levels.