What the hell?

July 11, 2008 10:31 PM

Why don't any drugs work for me?

I'm on like my 800th muscle relaxant/sleeping pill and they (all of the pills I've tried etc) still no no noticeable effect on me.

I even took 3 cyclobenzaprine 10 mg tablets or flexedril tablets. That's 3 times the recommended fucking dosage and I don't even feel sleepy. What the hell?

Seriously. It seems like this problem is related to every pill I take too (for anything), more than half of them just don't work at all. Is it possible to have a resistance to a ton of drugs? Is this some kind of medical condition? What is going on?!

posted by jumbotron08 to health & fitness (22 comments total)

I always find it annoying when ask.me insists everyone should go see a doctor, but I think this might be something that only your general practitioner (or even a specialist) could diagnose. If you prefer internet speculation, it might help if you could provide us more detail, such as:

-how old are you?
-any serious medical conditions?
-why are you taking muscle relaxant/sleeping pills?
-have you seen a doctor about this/these condition(s)?
-You say 'more than half of all pills you've ever taken don't work'. Can you tell us what you've taken and over what period of time (all your life? last ten years?)

We need more information.
posted by arnicae at 10:52 PM on July 11, 2008

Some people are more resistant to drugs than others (especially pain-killers), but you can see your doctor for specific concerns.
posted by amyms at 11:05 PM on July 11, 2008

I'm on like my 800th muscle relaxant/sleeping pill and they (all of the pills I've tried etc) still no no noticeable effect on me.

YMMV jumbotron08, but for me, I would take it as a sign I'd been taking too many.

Talk to your doctor about it.
posted by three blind mice at 11:07 PM on July 11, 2008

It's possible that you're overestimating the strength of the effects you're supposed to feel. It's also possible you're drugging yourself in other ways (think caffeine, in this particular case) that negate the power of the drug. It's also possible your pharmacist is slipping you placebos and ripping off the drug store they work for.

These are three no-need-to-see-a-doctor answers I can think of, off the top of my head. I will say that I have a bit of similar history with novocaine; specifically, when I go to the dentist I end up feeling the pain of the work, because no matter how much they inject me (and believe me, I've had one dentist walk in repeatedly every fifteen minutes, go punch-punch-punch-punch-punch in seemingly random places in my gums, then get frustrated as hell each time he came back and found I could still feel it) I never go numb in one half of my jaw.

So it's not impossible that these drugs don't effect you, but if the type and number of different drugs is as broad as you suggest, it seems awfully unlikely.
posted by davejay at 11:08 PM on July 11, 2008

IANAD but Cyclobenzaprine is not a sleeping pill - you'd have to take a significantly higher dose than 30mg to experience a sedative effect, probably more than 100mg. What are they prescribed for, because they pretty much won't aid sleep? Drug resistance is not uncommon and can be related to genetic factors, but it's unlikely to affect so many combinations.
posted by Blacksun at 11:09 PM on July 11, 2008

by "it seems awfully unlikely" I don't mean to imply you're lying, but that it's either a non-medical reason or something you really need to speak with a doctor about.
posted by davejay at 11:09 PM on July 11, 2008

I have had the same experience. Nothing works on me: sleeping pills, Vicodin, muscle relaxants, novacaine.
(IANAD) Usually being resistant or tolerant is an effect of abuse of painkillers, etc, but I had never taken any of them before, nor abused them. My doctor chalked it up to "just one of those things." So it may just be natural. Don't take more than the recommended dosage, even if it has little or no effect on you as it's not good for your body.
To help me sleep, I got a noise machine.
posted by wilde at 11:28 PM on July 11, 2008

Please don't take 100mg of Cyclobenzaprine. I don't know where Blacksun got that number but I'm not sure what would happen at that dosage. I doubt it would be pretty.
posted by Justinian at 11:41 PM on July 11, 2008

Have you ever tried or heard of Melatonin? It's all natural, and works for me within 5 minutes. It makes your body feel the way you feel when you first wake up and want to go back to sleep. It has no side effects, and doesn't make you drowsy. You can actually take it before a half hour nap and wake up feeling like you didn't take anything.

You can get it at Trader Joe's if there is one near you. They sell a bottle with 100 chewable peppermint tablets (even tastes good!) for $3.99. It's totally worth a try!
posted by Andrea2880 at 11:59 PM on July 11, 2008 [5 favorites has favorites]

It's not unheard of for someone to have a whacked-out drug metabolism that won't allow them to receive any benefit from certain medications. Unfortunately, you may be suffering from that, and I'm not aware of any way to "fix" it.

Also, I agree with Justinian about the 100mg of cyclobenzaprine thing. Taking that much would cause you some serious fuckin' problems, and the best thing you can do is take the prescribed dosage as to not cause serious side-effects. For what it's worth, though, I have seen cyclobenzaprine prescribed (off-label, obviously) as a sleep aid since it's dirt cheap.
posted by Wasabunchi at 12:08 AM on July 12, 2008

Dear God, Yes. DO NOT take 100mg! Should have made that abundantly clear.
posted by Blacksun at 2:10 AM on July 12, 2008

I don't know where Blacksun got that number

British National Formulary. Standard issue to UK medics and associated fields. Side effects in doses above 100mg include drowsiness. No recorded UK fatalities from OD in doses above 250mg, though you would feel like absolute crap, it is thankfully a relatively safe drug.
posted by Blacksun at 2:17 AM on July 12, 2008

Here's some info about genetic variations that affect people's reactions to drugs. Pretty much as soon as you take a drug, your liver starts clearing it out. It uses a handful of enzymes to do this (CYP3A4, CYP2D6, and a bunch of others).

If your body makes lots of a specific enzyme, a drug might go away very fast. It's complicated for a variety of reasons:

* A drug may be metabolized by more than one enzyme
* If you are a fast metabolizer (make a lot of the enzyme), the drug goes away fast.
* If you are a slow metabolizer (make a tiny amount of the enzyme) the drug hangs around for a long time, and a "normal" dose taken regularly is likely to result in too much drug, since you still have drug left over in your system from dose 1 & 2 by the time you take dose 3.
* Some drugs are prodrugs and don't turn into the active form till the enzyme gets to them. The classic example is codeine which actually turns into morphine in the body - but doesn't if you lack the CYP2D6 enzyme. Slow CYP2D6 metabolizers are more common in asian populations so the classic example in pharmacy school was the asian patient who is complaining that the painkiller their dentist gave them isn't working.
* Drugs get metabolized into other things, which may be good (codeine --> morphine) or may be bad (alcohol --> acetylaldehyde --> acetic acid). The famous "asian flush" after drinking is a result of low levels of alcohol dehydrogenase, which is responsible for getting the nasty acetylaldehyde out of your body. If you can't get rid of it, you are poisoning yourself by drinking.

As soon as anything you've taken by mouth gets absorbed from the GI tract, the blood gets shunted over to the liver for first pass metabolism. This is one reason why you can't take all drugs by mouth - the liver would destroy too much of the drug on first pass metabolism.

So one possibility is that your a fast 2D6 metabolizer and it's making your cyclobenzaprine go away too fast. My link says that about 7% of people fall into this category. It's just something to think about if you've noticed this with other drugs too. It's probably not every last drug on earth, just those affected by that one enzyme. Obviously I have no way of knowing this is really the case, and if it's a big deal you might want to consider getting tested to see what's up with your physiology. Good luck!! I know it must be horrible to not have the Flexeril work.
posted by selfmedicating at 6:14 AM on July 12, 2008 [3 favorites has favorites]

For what it's worth, I have the same problem with lots of drugs, including cyclobenzaprine. It's not a tolerance that has built up over time; the resistance was there from the beginning. I have a long list of drugs that either don't work for me or require a much higher dose than usual to be effective. Hell, I've even woken up from general anesthesia twice. I've asked my doctors about it and the only response I get from them is "well, different people react differently to different drugs."

I figure drug-resistance is my superpower. If only I could find a way to use it to fight evil or something.
posted by baho at 7:52 AM on July 12, 2008

I will say that I have a bit of similar history with novocaine; specifically, when I go to the dentist I end up feeling the pain of the work, because no matter how much they inject me (and believe me, I've had one dentist walk in repeatedly every fifteen minutes, go punch-punch-punch-punch-punch in seemingly random places in my gums, then get frustrated as hell each time he came back and found I could still feel it) I never go numb in one half of my jaw.

DaveJay: You may already know this, but just in case ... there are alternatives within the same family. Septocaine is what does it for me. I started requesting septocaine instead of lidocaine about two years ago after a conversation with my dentist, and it's made a huge difference when I get dental work or minor dermatologic surgery.
posted by spaceman_spiff at 9:15 AM on July 12, 2008

Yeah, pain pills (rx) just don't work on me either. I feel kinda wonky taking tylenol, but I'm fine with advil. I really doubt seeing a doctor would help--these things are extremely person-specific. They might give you another rx, but if you are older than 20 you've probably tried all the options. For the record: I am a normal weight, pretty short female.

You basically just have to suck it up when normal people can take vicodins. And if you want to get to sleep, try benadryl. That shit is potent. Also, I find novocaine to be highly inebriating and very pleasant (whereas most people just feel nauseated and dulled ... i love the shit). Of course we are two different people, so YMMV.
posted by shownomercy at 11:00 AM on July 12, 2008

Do you drink a lot?

I have a friend with a similar situation, his doctor said that it was very, very hard to knock him out for surgery, and it was likely due to his drinking habit.
posted by sondrialiac at 11:37 AM on July 12, 2008

Sondriliac: You or your friend wouldn't happen to have more information about the correlation between a drinking habit and resistance to narcotics, would you? This particular relationship has been plaguing my head and I'd love to learn more about it.
posted by oreonax at 2:46 PM on July 12, 2008 [1 favorite has favorites]

@oreonax - the link is liver enzymes. Alcohol potentiates a lot of enzymes, meaning the liver has to work so hard to metabolize the alcohol that it ends up producing a lot of enzymes, which then go on to eliminate other things from your system. One thing they did tell us in pharmacy school is if you run into someone who seems to need big doses of everything, keep in mind that alcoholism could be a factor.
posted by selfmedicating at 3:33 PM on July 12, 2008 [1 favorite has favorites]

Also, there could be tolerance in the brain as well-- while opioid painkillers work directly on opioid receptors, alcohol also seems to activate them less directly (hence the use of naltrexone, which blocks opioid receptors, in alcoholism treatment) and this can induce some degree of tolerance, called "cross tolerance."

Note: the most dangerous combination of psychoactive drugs is an opioid plus another drug in the "depressant" class such as alcohol and/or sleeping pills/anxiety meds (for example, benzodiazepines like valium, xanax, etc.).

The vast majority of overdoses are not people taking too much of a drug they already take-- tolerance usually prevents both this, and the high people are seeking by doing so. Cross-tolerance is less reliable. These drugs synergize and one plus one can equal ten.

If you do not want to die, avoid such mixtures and if you insist on combining multiple depressants even in a single class (say oxycontin plus methadone), have a friend with naloxone (opioid antidote, please excuse self-link) nearby or at the very least, be extremely careful about dose.
posted by Maias at 4:23 PM on July 12, 2008 [1 favorite has favorites]

@selfmedication - many thanks. One last question, (and if this is an inappropriate derail I can take this to MeMail) does this apply only during active alcoholism or do the self-regenerating properties of the liver make this a transient effect that manifests during heavy drinking?
posted by oreonax at 10:47 AM on July 14, 2008

d'oh. well, that was a badly previewed followup question. sorry.
posted by oreonax at 10:48 AM on July 14, 2008