How do drug users gain tolerance for a drug?

In summary, the substance being abused (in this case, alcohol) causes the cells to become tolerant to its effects, meaning that the amount of effect that the drug has on a person is no longer constant. This can be problematic for people who are using drugs for long periods of time, as the higher doses needed to achieve the same effect can lead to increased levels of carcinogenic byproducts in the body.
  • #1
confusedbyphysics
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We're studying cell signaling and signal transduction in my biology class, and we discussed this briefly in class but I don't really understand it.
Why does the affect of a drug decrease the more a person uses it?
I don't understand. If someone takes a drug more, wouldn't there be more of the drug in the cells, thus increasing the effects of the drug?
Sorry if this is a stupid question, but thanks for anyone that can help me understand.
 
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  • #2
I don't know the exact mechanism down to the molecular level, but essentially sometimes the receptors on the nerve membranes that bind the active compounds released by the drug are down regulated. One way of doing this is via endocytosis, which means that a piece of the membrane with the receptors, which usually are transmembrane proteins, is pinched off and taken into the cell. Then you get less receptors on the membrane and thus less sensitivity to the active compounds of the drugs. I didn't include any specific names of any proteins or a specific example. But if someone else knows a specific example I would like to read about it as well.
 
  • #3
One specific example is in the addiction to opiates. In the locus ceruleus, it appears that the opiate receptors do get down-regulated. This process is called desensitization, meaning that the neurons are now less sensitive to the same amount of drug. However, it appears more complicated than simple down-regulation of opiate receptors. The high levels of drug lead to a lot of stimulation of the cells which in turn actually physically changes the neurons. As far as I know, this is still a well studied problem.
 
  • #4
So something inside the cell is happening as well? Maybe in the signal transduction pathway, something is getting expressed less/more or something new is getting expressed. I'm just speculating.
 
  • #5
this is kind of ironic... i read this question last night and then my prof talked about this in class today

Drug tolerance has to do with the smooth endoplasmic reticulum in cells. The smooth E.R. takes insoluble substances and through hydroxylation reactions (changing molecular oxygen to generate hydroxy groups) they turn insoluble substances into soluble substances.

The smooth E.R. rapidly proliferates to get rid of the toxic substance and so the next time the drug is given, there is more smooth E.R. so it can get rid of the substance more quickly thus more is needed to create the same effect.

The main concern with this and long term drug use is that via the hydroxylation reactions, carcinogenic (cancer causing) byproducts can be formed...
 
  • #6
chantella28 said:
this is kind of ironic... i read this question last night and then my prof talked about this in class today
Drug tolerance has to do with the smooth endoplasmic reticulum in cells. The smooth E.R. takes insoluble substances and through hydroxylation reactions (changing molecular oxygen to generate hydroxy groups) they turn insoluble substances into soluble substances.
The smooth E.R. rapidly proliferates to get rid of the toxic substance and so the next time the drug is given, there is more smooth E.R. so it can get rid of the substance more quickly thus more is needed to create the same effect.
The main concern with this and long term drug use is that via the hydroxylation reactions, carcinogenic (cancer causing) byproducts can be formed...

That's something from very old literature, and, as far as I know, only applies to alcohol effects on liver cells. The liver increases production of alcohol dehydrogenase (a mechanism involving the smooth ER), which helps to metabolize the alcohol faster. But that's not truly tolerance as much as more rapid clearance to keep blood concentrations of ethanol lower.

Drug tolerance, where higher doses reaching cells have less effect on the cells, as occurs in the process of addiction, is related to the availability of the receptors for that drug. As has been described above by others, part of the mechanism for tolerance is at the level of receptor availability, such as via a change in the rate of receptor internalization, recycling, or de novo synthesis. There may also be a change in how the signal transduction pathways respond following receptor binding. So, it's certainly not a simple process. Understanding this is not only important for treatment of addiction, but also for preventing tolerance/addiction in patients being treated with drugs for reasons such as pain management.
 

1. How does tolerance to a drug develop?

Tolerance to a drug develops when the body becomes less responsive to the effects of the drug over time. This means that a higher dose of the drug is needed to produce the same effects as before. This happens because the body adjusts to the presence of the drug and becomes less sensitive to it.

2. What causes an individual to develop tolerance to a drug?

Tolerance to a drug can develop due to a variety of factors, including genetics, frequency and amount of drug use, and environmental influences. Certain drugs may also cause physical changes in the body that contribute to the development of tolerance.

3. How long does it take to develop tolerance to a drug?

The amount of time it takes to develop tolerance to a drug varies depending on the individual, the drug, and the frequency and amount of use. Some people may develop tolerance quickly, while others may take longer. In general, the longer and more frequently a drug is used, the faster tolerance will develop.

4. Can tolerance to a drug be reversed?

Yes, tolerance to a drug can be reversed by taking a break from using the drug. This allows the body to reset and become more sensitive to the drug again. However, if drug use continues, tolerance will likely develop again.

5. Are there any ways to prevent or delay the development of tolerance to a drug?

There is some evidence that alternating between different drugs or using drugs in smaller doses can delay the development of tolerance. However, the best way to prevent tolerance is to avoid using drugs altogether.

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