Immunity to Drugs: Is Complete Resistance Possible?

[easyrider]

Hi yall, just had a question that got me thinking. Say you do a drug that builds tolerance, eg alcohol or opiates. If you took an extreme amount chronically is there any way to become completely immune to it to the point no amount of the drug will affect you at all?

 

[mgb_phys]

It depends on the mechanism of the drugs activity.
Tolerance can occur by either building up a stock of whatever breaks down the drug - so you become more able to deal with it. Or it can mean you gradually destroy the sites the drug acts on so that you need more to dose to have an effect.

Either way there is going to be a level of aything that can kill you.

 

[jim mcnamara]

It does change the dose-repsonse curve - as mqb indicates. But there is no way to know ahead of time what the ultimate result would be. Generally, really high doses of things like ethanol can have very deleterious (sometimes fatal) side effects. For example high doses of ethanol are fatal because it can interfere with the autonomic nervous system - heart rate, breathing, etc. leading to respiratory failure - ie., death

There is a concept in toxicology: LD50 It measures the dose of a drug (or whatever) that will kill 50% of the oragnisms like rats, mice, or humans, that are exposed to that level. This is the MSDS sheet for absolute ethyl alcohol (ethanol):
https://fscimage.fishersci.com/msds/89308.htm Read the section about "Potential Health Effects"

Ethanol is drinking alcohol.

 

[Astronuc]

Hi yall, just had a question that got me thinking. Say you do a drug that builds tolerance, eg alcohol or opiates. If you took an extreme amount chronically is there any way to become completely immune to it to the point no amount of the drug will affect you at all?

I've never known anyone to be immune from drug effect. Chronically using (abusing) alcohol or opiates will result in a deterioration of the body and mind. The body adapts to a point, but organ damage and mental deterioration will occur.

Alcoholic liver disease. To many people, cirrhosis of the liver is synonymous with chronic alcoholism, but in fact, alcoholism is only one of the causes. Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person. In women, as few as two to three drinks per day have been linked with cirrhosis and in men, as few as three to four drinks per day. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.

http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis/

 

[easyrider]

So its in no way possible to become immune to alcohol? Because I saw in a series on tv where an alcoholic woman was drinking very heavily everyday and one day she couldn't get drunk anymore, I was wondering the validity of it.

 

[jim mcnamara]

easyrider - No. Like I said it can change the dose/response curve.
Alcoholics over time respond less to alcohol because they have in part damaged alcohol receptor sites. But she would still be very much impaired. And if she were that bad off, she would have shown lots of other really awful symptoms, something like maybe Korsakoff's Syndrome - a kind of babbling psychosis caused by vitamin deficiency (thiamine) usually associated with alcoholism. It would not be something TV-wachers would like to see.

The consequences of alcholism far outweigh "becoming partially immune", if that is even possible. There are alcohol realted dementias, central nervous system disorders, immune system problems, pancreatic damage leading to diabetes... you are looking at systemic damage. The whole body is hosed.

After smoking, alcohol abuse is the number two cause of excess mortality in populations under 50. For example, in New Mexico, 75% of all traffic accidents involving fatality have
at least one legally drunk driver involved in the crash.

I once did some human survivorship curve studies with McKinley County, NM data. There are so many alcohol-related fatalities (hypothermia, accidents of all kinds) in people 18-24 that the curve is unlike any human survivorship curve anywhere else. This was for the period 1970-1980.

 

[Spirochete]

The short answer to your question is no, read the following paragraphs for some clarification.

I don't have any studies at the moment to back this up, but I can tell you a little bit about opiate addiction. Unlike alcohol, it's not intrinsically harmful to any organ in the body. It does cause chronic constipation which can be harmful if not treated with stool softeners etc.

So in theory you can progressively increase your dose as tolerance develops and never experience any physically harmful effects. People with chronic pain and those on methadone maintenance for addiction are sometimes maintained like this. In addition there seems to be a maximum dose that people will plateau at if given an unlimited supply. Of course at this point most people aren't really getting any euphoria from it, they just need the stuff to feel normal and prevent going into horrible withdrawls. And who knows what level of psychological blunting they may experience.

Maintaining this level of addiction with an illicit, artificially overpriced supply of drug is virtually impossible, thus many addicts end up stealing or dealing to support the habit, still never reaching the plateau I described above with methadone. The end point is death or prison.

Benzodiazepines are similar to opiates in the ways I just described, except they don't cause constipation. Also withdrawl from benzos can cause seizures and death, whereas opiate withdrawl is just excruciating.

Some synthetic opiates have extra toxicity which prevents high dosing, they include propoxyphene (darvocet) and meperidine (demerol)

 

[Spirochete]

So its in no way possible to become immune to alcohol? Because I saw in a series on tv where an alcoholic woman was drinking very heavily everyday and one day she couldn't get drunk anymore, I was wondering the validity of it.

The woman may feel no subjective positive effects from drinking anymore, but she is continuing to do irreversable damage to various organs in her body, as another poster described. And by that time she's likely accumulated brain damage leading to diminished mental functioning. So by the time she stops getting drunk per se, she's being affected by alcohol 24/7.

 

[easyrider]

Spiro, what do you mean by the plateau on methadone? You mean they get to a dose where their tolerance stops increasing?

 

[denverdoc]

If I may butt in: generally methadone doses range from 50 to 150 mg/day. To put that in perspective, its somewhat more potent that the percocet you might have been prsecribed for pain. Doses can get much higher, say three times that, but there is no reason to increase them at the clinics. This is a maintenance dose with no high intended. Now left to their own devices, opiate users can often push doses far further. A good example is with Fentanyl, or even Oxycontin--similar to percoset--where I have seen self precribed doses reach beyond 500mg.

 

[Moonbear]

Just to help summarize the points made above for the sake of clarity, when someone refers to "tolerance" to a drug, they are usually describing the neural effects...what the drug is doing to the brain or other parts of the nervous system...though it can be related to specific effects of the drug on other organs too. SPECIFIC effects is the key point, meaning the function of the drug on the receptors in cells that the drug targets. The availability of those receptors can change, which reduces the effects of the drug on those receptors and in turn, reduces the specific effects that drug usually elicits.

However, this does not alter the NON-specific effects of a drug, i.e., its toxicity on non-target organs. As was given in an example above, one can stop feeling the euphoria induced by a substance (alcohol or other drug), can stop feeling other effects of the drug (i.e., speeding up or slowing down of heart rate), but the liver is still trying to clear away the drug from the system and being damaged, the stomach is still being damaged and ulcerated, etc. So even if someone can "build up" to a dose that would lead to cessation of breathing or heart beating in a person who has never taken the drug before without those effects, they will still be slowly dying from the non-specific organ damage caused by toxicity of the substance at high doses.

Also, because the receptors that drugs are targetting in the brain are there because they have functions in normal physiology, the disruption of those systems by chronic drug use can also impair normal function. You may have noticed the chronic alcohol abusers who have a permanent tremor or spasticity of their movements, even when they are not "drunk."

 

[jim mcnamara]

..all this discussion based on a bad plot premise from a TV show, probably written by people with Fine Arts degrees.

This should be an indicator for all of the bogus content on TV that TV watchers take as real.