Why don't painkillers or caffeine affect me?
September 16, 2009 9:10 AM   Subscribe

No matter how much ibuprofen, acetaminophen or naproxen I have, it does absolutely nothing for me. No matter how much coffee I drink, I'm just as sleepy as ever. What gives?

This isn't just drugs in general. Melatonin puts me to sleep. Alcohol gets me drunk. Cigarettes make me jittery sometimes (although I've never, ever been addicted no matter how hard I "tried"... even a pack a day in college for a few months had no effect on me when I abruptly stopped).

I should point out a few things:

1) I do drink coffee a lot, but it's the same as with cigarettes. I can stop drinking it for weeks or months at a time, and I never feel any kind of withdrawal. When I start up again, it doesn't give me the intended effect at all.

2) Don't worry, I'm not popping entire bottles of Tylenol. I rarely take painkillers at all because they don't have an effect on me, so I don't think I have built up a resistance. Occasionally, when I get a truly horrible, brainsplitting headache, I try to take a painkiller in the hopes that something will happen. At that point, even when I take several times the recommended dosage, nothing happens to me at all.

3) I saw this post, but I don't think it answers my question.
posted by timory to Health & Fitness (26 answers total) 5 users marked this as a favorite
No idea about the caffeine, but Tylenol, aspirin and ibuprofin are not painkillers. Opiates are painkillers. What you're talking about are pain relievers. They work mostly by decreasing inflammation. Not all headaches can be handled by pain relievers, which is why people with chronic migraines are usually given something stronger (actually, they're often given some caffeine).

If you're having severe headaches often, you should see a doctor. It could be migraines. Have you noticed that you have less pain when you do drink coffee?

Alternatively, do you drink enough water? Being dehydrated will make you tired and headachey enough that no amount of aspirin or coffee will help.
posted by oinopaponton at 9:16 AM on September 16, 2009

Seconding dehydration as a possible point, and also seconding that you get your headaches checked out as possible migraines. Migraine-sufferers generally get little-to-no relief from over-the-counter acetometophen, ibuprofen, and the like.
posted by Tomorrowful at 9:19 AM on September 16, 2009

Another thing I guess I should have clarified - I drink tons of water. Two or three liters a day, at least. I'm also in good general health, lowish blood pressure, walk 3 or so miles a day, that sort of thing. Anything else I can add, just ask.

I've considered the migraine thing as a possibility, but I've only been put out of commission by my headaches maybe twice in my entire life. I always thought that migraines were so debilitating that a person suffering from them could barely move as a result. I almost never get headaches like that.
posted by timory at 9:28 AM on September 16, 2009

As far as I know, Tylenol is not an anti-inflammatory...

Anyway, caffeine doesn't really affect me because I have ADD. Maybe that's what's going on with you.

DO NOT take several times the recommended dose of Tylenol. It is horrible for your liver.
posted by kathrineg at 9:28 AM on September 16, 2009

I rarely take painkillers at all because they don't have an effect on me, so I don't think I have built up a resistance

You can't really build up a resistance to pain relievers like acetaminophen and ibuprofen. There's no analog to opiate tolerance at work there.

Occasionally, when I get a truly horrible, brainsplitting headache, I try to take a painkiller in the hopes that something will happen.

The kinds of drugs you are taking are essentially COX inhibitors, though the precise mechanism of action of acetaminophen is different than that of the NSAIDs (ibuprofen, naproxen, etc). It is not surprising that if one does not work, neither do the others. You should see a doctor to determine whether these are migraines and thus whether other, prescription medications would be appropriate.

At that point, even when I take several times the recommended dosage, nothing happens to me at all.

Do not do this. Acetaminophen, ibuprofen, naproxen, etc have a maximum therapeutic dosage. You can't just keep dialing up the dose until either effectiveness or unconsciousness is reached like, say, morphine. More than about 1000mg of acetaminophen or 800mg of ibuprofen will do no more good and can do substantial, even life-threatening harm.
posted by jedicus at 9:32 AM on September 16, 2009

No idea about the pain relievers, but if you're sleepy after caffeine, it could be a sleep disorder like sleep apnea and/or mild narcolepsy. Or, like kathrineg says, it could be ADD - I know someone who drinks POTS of coffee and still falls asleep around 6 pm.
posted by desjardins at 9:34 AM on September 16, 2009

I'm confused--are acetaminophen and ibuprofen supposed to keep you up? The issue here sounds like an iron deficiency or maybe you're just not getting enough calories. I'd strongly suggest speaking to a doctor, because it could be a much bigger problem.
posted by Aanidaani at 9:35 AM on September 16, 2009

I'm not sure this answers your question, but re: the migraines: migraines are not always debilitating. They can vary pretty significantly in severity. Sometimes you can't do anything but take some codeine and lay down, but other times you can function (not happily, but function). I sometimes get migraines that are everything but the headache- light sensitivity, "brain fog," nausea. In all of these cases, ibuprofen and naproxen are of no help whatsoever. Like I didn't take anything at all. Acetomenophen helps some, but opiates, caffeine, and sleep help the most. You might be having less severe migraines and thus the advil wouldn't help at all.

Next time you get a nasty headache, try a Tylenol or Tylenol-3 if you have it, a cup of coffee, and a dark room. If you feel better, you'll at least know why the ibuprofen was useless.
posted by ohio at 9:37 AM on September 16, 2009

Aanidaani: Sorry, no, the two things are unrelated. Pain relievers don't relieve my pain. Caffeine doesn't wake me up (doesn't put me to sleep either, for those who mentioned this). It's just a pattern I noticed that drugs that should have an effect on me don't.
posted by timory at 9:38 AM on September 16, 2009

Not all COX inhibitors work the same on all people. Some work for me and others don't. Mobic and Bextra (taken off the market) worked best in my case. You may need to experiment to find if any work for you. But as posted above, these are not ordinarily headache drugs.
posted by Obscure Reference at 9:41 AM on September 16, 2009

Are you unaffected by all drugs? have you tried drugs which give a perceived "high?" Have you smoked cannabis? did you get high? have you ever used a painkiller like Percocet or Vocodin? Did you feel the effects of those?

It's possible that analgesics don't affect you due to some malfunction in your peripheral nervous system, or some resistance to neurotransmitters.
posted by ichthuz at 9:57 AM on September 16, 2009

Acetaminophen (e.g. Tylenol) is not an anti-inflammatory. NSAIDs include naproxen and ibuprofen.)

As for why they don't affect you, metabolisms differ and some drugs don't work well for some people. Allergy season has started early here, and I'm regretting that antihistamines don't do anything for me.
posted by Zed at 10:02 AM on September 16, 2009

Analgesics are so variable in their effects from person to person that it doesn't necessarily mean anything significant about your personal biochemistry if they don't work for you. Aspirin does nothing for me, unless I have tendonitis which it does handle for me; naproxen doesn't work for my headaches, but ibuprofen or acetaminophen sometimes do, if I take a large enough dose.

It's generally safe to take up to 1000 milligrams of acetaminophen at a time, if you're not taking anything else and don't make a habit of it. Ibuprofen is reasonably safe up to 800 milligrams at a time, which is the standard prescription strength.

Migraines can be severe or mild. Medication works best if you take it at the very beginning of a migraine, and is often not effective if you wait too long, but, if you get mild migraines, it can be hard to tell at first whether it's bad enough to justify taking anything for it. You might want to get a sample of imitrex from your doctor to try the next time you get one of those horrible brain-splitter headaches.
posted by Ery at 10:13 AM on September 16, 2009

Not everybody reacts to NSAIDs or analgesics the same way, and most docs know this. A lot of people don't, however.

1) ibuprofen, acetaminophen, and naproxen are not the same kind of drug. Ibuprofen and naproxen sodium are NSAIDs (antiinflammatories). Ibuprofen and naproxen don't work for me, either. (Ibuprofen actually *gives* me a headache.) Acetaminophen is an analgesic, and it sometimes works for me, for some kinds of pain. DO NOT take over the maximum recommended dosing of *ANY* OTC med.

2) I have often described myself as immune to caffeine. DaughterR is the same way. According to the psychiatrist we saw when getting SonR's ADD dealt with, no responsible doctor would diagnose her or me with ADD or ADHD.

My docs all chalk it up to personal differences, and have worked with me to find an NSAID that does work when I need it to.
posted by jlkr at 10:54 AM on September 16, 2009

Anyway, caffeine doesn't really affect me because I have ADD. Maybe that's what's going on with you.

Caffeine doesn't affect me in the way that it does most people--it calms me down and helps me concentrate rather than waking me up and making me jittery. I've been told that this is because of my ADD. It's not that it doesn't affect me at all, it's just different. (Not arguing with kathrineg, just adding a different perspective.)
posted by Aleen at 10:57 AM on September 16, 2009

I've got the same problem -- only some opiates affect me (for example, Vicodin might as well be sugarcubes, yet Percocet works), Tylenol and the like are pointless, I have also been able to quit smoking abruptly with no issues... and my dad is the same way on all counts, so I think there must be some genetic component to it. As an additional data point, I am a migraine person, too, who had to work for years to find migraine meds that actually do anything for me.

Unless this is getting in the way for treating something, I wouldn't worry about it too much. I finally found a doctor who "gets" migraine patients and understands that pain meds often affect us differently. That he's a DO and not an MD may have something to do with it -- a surgeon who worked on me previously flat out accused me of being drugseeking when I asked about the difference between Vicodin and Percocet, and why one works on me and the other doesn't.

Piece of advice: unless you know the doctor you're speaking with, be prepared to explain that this has been happening to you for some time, and frame it in the "why is this, and can you make a recommendation?" way rather than saying "X doesn't work for me," because in my experience, most doctors freaking hate that.
posted by bitter-girl.com at 11:14 AM on September 16, 2009

Coffee makes me tired. I *think* this is because the physical effect it had on me was negligible, but the placebo effect I got from my body/mind associating it with being tired was significant.

Different substances affect different people to different degrees. Some more, some less, some not at all. I wouldn't really worry about it too much.
posted by glider at 11:32 AM on September 16, 2009

Also, once you've convinced yourself that the drugs are ineffective for you, you've got a variation of the nocebo effect going in which the drugs have less of an effect because you are so sure they are useless. So keep thinking positively! (gah, I sound like some The Secret-reading whacko there, but you get the point...)
posted by zachlipton at 11:40 AM on September 16, 2009

You might actually try *less* water for a little while. There is such a thing as over-hydration.
posted by Citrus at 12:17 PM on September 16, 2009

It's generally safe to take up to 1000 milligrams of acetaminophen at a time, if you're not taking anything else and don't make a habit of it.

Not worth the risk--the FDA voted to limit the maximum single dose to 650 milligrams.
posted by kathrineg at 12:31 PM on September 16, 2009

Caffeine doesn't affect my level of awakeness either. I almost never drink coffee or and only have caffeine containing soda maybe 2x a week, so I haven't built up some kind of superhuman resistance.

Sometimes acetaminophen or ibuprofen don't work on my migraines. They can help, but it won't relieve it entirely. I discovered during childhood that drinking caffeine when I had a migraine helped, so to get through school I would self-medicate with Mountain Dew. I still do that, though there are combo pills you can take with caffeine added.

That said, migraines vary widely, and they don't always knock you on your ass. I've had my share of those where I need a dark room and sleep ASAP, but during others I can function on some level of normal as long as I have some caffeine and ibuprofen to take the edge off. Maybe a pair of sunglasses.
posted by cmgonzalez at 12:59 PM on September 16, 2009

If it makes you feel any better, your post exactly describes me as well. I've wondered about these phenomena for a long time.
posted by derogatorysphinx at 1:02 PM on September 16, 2009

It would help if you posted what pain are you trying to get rid of?
posted by majortom1981 at 1:12 PM on September 16, 2009

At the moment I'm not trying to get rid of any pain. I'm just asking why it is that so many common drugs have no effect on me.

Yes, I get a high from drugs that are meant to give a high. Resistance to neurotransmitters gives me pause... I've been on some form of anti-depressant for over 10 years. Is that relevant in any way?
posted by timory at 2:44 PM on September 16, 2009

It's quite possible that you have an unusual variant or variants of the liver enzymes that metabolize these particular drugs. These are called things like CYP 2D6-- that particular one metabolizes quite alot of drugs and if you are a "fast metabolizer" your liver might be deactivating the drug before it can have an effect.

Google Cytochrome p450 for more info. You can get genetic tests to determine if you have common mutations here but they are expensive.

It gets complicated because some drugs actually signal the liver to create more of their own metabolizers while other drugs do the opposite or affect different ones and so interactions are quite tricky to predict.
posted by Maias at 3:58 PM on September 16, 2009

Oh, and yes, the antidepressant is relevant-- if it's Prozac, if I recall correctly, that does something to CYP 2D6, I forget what but it could "tie up" the pathway and some drugs must be metabolized *before* they can work, so if there isn't enough of the enzyme to do this, they won't work.
posted by Maias at 3:59 PM on September 16, 2009

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