Could I be resistant to all opioid drugs?
December 20, 2012 10:06 AM   Subscribe

Biochemistry Filter: I believe I have some kind of resistance/insensitivity to opioid painkillers, although I have not been able to verify that this is a medically known phenomenon. I am due to give birth soon, and I am concerned with the possible efficacy of drugs that may be administered for labor pain. Do you have any experience with this in yourself or others, or can you comment on the chemical plausibility of it?

On a couple of occasions I have been prescribed codeine or hydrocodone for pain relief and/or as cough suppressant. Both times, taking the medicine, even repeatedly and at increased dosage, had no effect on me whatsoever—no relief, no feeling of being loopy or high, no drowsiness. It was like I had simply never taken the medicine at all.

My brother reports the exact same experience with hydrocodone, so I am inclined to believe that this is something genetic and that I am not imagining it. Neither of us has ever used opioid drugs recreationally (or almost any drugs at all), so it is not an issue of having built up a tolerance. I can't find any reliable medical information on people being insensitive to these particular drugs or to the entire class of medications; however, I have found posts on health sites where some people anecdotally report similar experiences.

My concern right now is that I am going to give birth to my first child in about a month. I will be attended by a midwife, and I am interested in trying to have a natural (i.e., unmedicated) birth, but I am also kind of terrified about it. The birth center where I will deliver is in a hospital, so whatever I decide during labor about whether to have or not have medication will be available and honored.

From what I have read, injected narcotics for pain relief pose fewer possible complications and interference with labor than an epidural (this is from a pro–natural birth perspective; I'm not super interested in discussing this point), so if I do choose to have medication, I would prefer this route. However, since the commonly administered drugs seem to be fentanyl, butorphanol, and other opioids, I am worried that they may not work on me, and I assume there's no way to find out in advance.

If you are in the medical field, have you ever heard of a general opioid insensitivity? Is the issue more likely to be one of metabolizing the drug, or a problem with the action of opioid receptors, and would that have any bearing on whether an insensitivity to hydrocodone would extend to the entire class of opioid drugs?

Obviously I will discuss this all with my midwife, but as she is not an MD or a pharmacologist, I'm not sure how much this topic will be in her wheelhouse, so I look to the hive mind for broad experience.
posted by zadermatermorts to Health & Fitness (20 answers total) 3 users marked this as a favorite
Like you, I am highly resistant to many types of pain medication, especially opioids. My GP is well aware of this, and I do have to discuss my history with other doctors if they are prescribing pain meds. It is true that some meds work better than others, but I build up a tolerance after two or three doses, so hunting around for "the" pain med has not been successful. Luckily, I have a pretty high pain tolerance (although this may just be me getting used to being in pain). I have heard that this may have to do with being red-headed, but I don't know that there have been any good studies to that effect. My father was also highly resistant, so there's some support for the genetic aspect to support you and your brother.

So, it doesn't sound like you're alone. I'm hoping to hear some medical professionals pipe up with better data.
posted by blurker at 10:24 AM on December 20, 2012

When I did my 22 and me analysis, it told me that I had a gene that caaused a non-standard reaction to opiates. I forgot all about it until I gave birth, when the Demerol they gave me caused hallucinations but no pain relief.

So it's definitely a thing, and I'd recommend staying clear based on my experience. Things were already tense enough due toy inexperience without unpredictable drug reactions getting in the way!
posted by snickerdoodle at 10:28 AM on December 20, 2012

Some things that might help refine your search for information are that this is not really biochemistry-filter but anesthesiology-filter, you are not interested in your opiate resistance but your opiate sensitivity, and your midwife as well as their medical backup should absolutely be willing to spend quality time discussing this with you. One of the big benefits of delivering in a hospital is that there should be a staff anesthesiologist right there.

Also, the expected effectiveness of pain medication has a MASSIVE effect on the actual effectiveness; if you go into labor expecting no drug to help manage your pain, then any drug is much less likely to help. If only for this reason I'd encourage you to completely ignore the anecdotal reports you'll find all over the internet and will no doubt find in this thread because anecdotes are really effective at creating subconscious expectations but not really effective at all for helping make rational decisions about care. That said, Human variation in opiate sensitivity is a thing, and has been shown to be heritable in mice at least. You're probably not crazy and this is a really good thing to know about yourself.
posted by Blasdelb at 10:46 AM on December 20, 2012 [1 favorite]

Do you have red hair, or do you have that kind of ancestry lurking there in the background somewhere? That could be one reason why:
When animals and humans experience pain, their brains release natural opiates similar to morphine. In most cases, however, the MC1R gene produces a protein that interferes with the efficacy of those substances as well as of artificial painkillers. What Mogil found is that the variant of MC1R that causes red hair also appears to allow these opiates to work unimpeded. As a result, redheads can withstand up to 25 percent more pain than their blond and brunet peers do before saying "stop."
posted by un petit cadeau at 10:52 AM on December 20, 2012 [1 favorite]

I don't have experience with the opiates issue, and I hope someone knowledgeable who does will jump in soon with some helpful suggestions. But as someone who has done the natural childbirth thing, and would do it again, and also as someone who has talked to a LOT of other mothers who had various childbirth experiences, I just wanted to address the (very natural and reasonable) terror you express:

The pain of childbirth IS terrible (don't believe those gurus who say otherwise; I think their memories have been edited by the glow of motherhood, or by a desire to sell books and classes -- take your pick). For me in particular, because I had unnaturally strong contractions and adhesions from an old surgery, it was really like hallucinatory level sort of pain. But I would willingly endure it again -- and with a lot more confidence! The pain is a very different sort of pain than trauma pain. It's not alarm pain (like "I just broke my leg" pain. It's more like marathon running pain. It's not unexpected; it's pain with a purpose. If you can keep your mind focused on the purpose, in my experience and in the experience of many women I've talked to, whether or not you have the support of medication, the part of your brain that knows what to do -- that same part that would let you walk through a burning house to rescue your baby -- takes over and helps you get through it. And you will not necessarily view the experience of the pain as a negative thing afterwards -- the women I know who have negative / traumatic memories of childbirth mostly had some other bad thing besides normal, healthy labor going on (a risk to the baby, an injury during the birth, a terrible doctor, etc.).

If you do decide you need medication (which, for the record, is a choice I totally support, because, again, the pain is real, and people who won't want to put up with it should not have to) and that medication fails to help, you will still get through it. I know women who really, really wanted an epidural or other medication right from the very start, and who, for whatever reason (couldn't get to the hospital in time; hospital anesthesiologist was too busy; super fast labor) could not get one, and they were unhappy about it, but they were okay.

It helps a lot to have helpful people surrounding you. It helps to feel like you are in respectful and safe hands. It's great that you have a midwife -- that will make a huge difference! It sounds like you have a really good setup with the birth center located in a hospital, too.
posted by BlueJae at 10:53 AM on December 20, 2012 [4 favorites]

I had my first kid--9lb 6 oz, with no medications, not even an epidural, and yes, it hurt like hell, but it wasn't unbearable (and I had back labor). Everyone is different, of course, but it sure beat the C-section I had the 2nd time around. I'm pretty sure that with most vaginal deliveries you can get a local epidural, not a general knock-out drug.
posted by Ideefixe at 10:57 AM on December 20, 2012

Thanks so far, all. No red hair in my family, although that is an interesting link.

Blasdelb, can you elaborate on the difference between resistance and sensitivity? Do you mean that the effects of the drugs are more relevant than their mechanism? I guess I am interested in the mechanism of resistance for curiosity's sake, and maybe to determine whether different drugs may be different in molecularly relevant ways. But I realize anything anyone on the Internet could say about that would only be speculation.

Maybe I should post a question next week for non–New Agey stories of natural birth. Information like "it is a different sort of pain than trauma pain" is SO much more helpful and confidence-building to me than the "I imagined my vagina opening like a flower" stuff that I have books full of. So, thanks.
posted by zadermatermorts at 11:19 AM on December 20, 2012 [1 favorite]

My experience with pain medication (specifically, Vicodin, and comparing that to over the counter things like Ibuprofen or Tylenol) is that the type of pain makes a big difference in how effective a specific drug is. For example, when I had my wisdom teeth out Vicodin was amazing, clearly superior to anything else I've had. On the other hand, for me it's less effective than Ibuprofen when it comes to period cramps. Go figure.
posted by anaelith at 11:25 AM on December 20, 2012

My dad recently had both knees replaced with artificial joints, one in Feb, one in October. In February he was dopey and sickly afterward, and it took several days to figure out it was the opiates. In October, at his request, they gave him non-opiate pain relievers (demerol? something like that) and he experienced less pain, more lucidity, and just generally recovered faster. No red hair in the family, but I also have found that opiates mostly make me feel faintly high and sick - I find NSAIDs more effective for me. Talk about it with your midwife and other medical folks beforehand - if they're like his surgical team, you won't be the first such person they've dealt with.
posted by ldthomps at 11:27 AM on December 20, 2012

I wish I could find a link for you, but I recall reading an article about the history of morphine use as a painkiller, and modern knowledge that morphine is not effective for some people, and that the probability of its being ineffective is higher in women than in men (this leading to women going through medical procedures with basically no painkillers, which is what the historical article was about). My quick googling only turned up this article about gender differences in rats, which includes mention of (but not a link to!) a study indicating that morphine has a stonger effect on men than women. Since this is because of differences in opiate receptors in the brain, this would seem to apply to the whole class of drugs. It seems like a "known thing" that opiate-based drugs may not work well; though like many medical studies, it also seems like some doctors' beliefs may or may not include those studies - so be willing to talk to other doctors if necessary.
posted by aimedwander at 11:30 AM on December 20, 2012

I experienced labor up to 100% effaced and pushing, and the pain was more work/ effort than other pain I've experienced. Opiods for surgical delivery worked very well. If your labor staff is not helpful and does not treat your concerns seriously, complain.

You may be among the 25% or so who have a surgical delivery. First, talk to your doctor. Assuming you've chosen a hospital, ask to speak to someone in the anesthesiology dept. about your concerns. Anesthesiologists really don't want you to feel pain, and even if you get a different person than the one you spoke to, you and your labor partner will be better prepared and more knowledgeable. Your labor partner is your critical advocate.
posted by theora55 at 11:47 AM on December 20, 2012 [1 favorite]

I am a redhead and have a non-standard reaction to opiates (Demerol and Codeine make me hallucinate but have no real effect on the pain).

I have given birth twice in the last 15 months without pain medication*. Once at home, once at a hospital with a tub. I just wanted to agree with BlueJae's experience (it's a different kind of pain, and yes, it hurts terribly, but not unbearably) and chime in that I had access to a jacuzzi tub for the end of my second labor and it made such a tremendous difference on how I dealt with the contractions. I think part of it was just experience, and part of it was that the water really, really helped me not fight the contractions but actually relax into them and let my body do the work. At one point I was actively trying not to push because I didn't want to have to get out of the tub (but didn't want to give birth in the tub either) and the baby moved down quite a lot anyway. I ended up giving birth 45 minutes after getting in the tub, 1.5hrs after getting to the hospital. That was a light bulb moment for me. Second labour was harder and the actual birth was a lot easier, and the water helped a lot. Just sharing that so you know there are ways of managing the pain that don't involve opiates.

*For both of my pregnancies it was always in my plan that if I felt I needed pain relief, I would totally ask for it. No martyr bullshit**. I was about five minutes away from asking for it when my second baby crowned and I realized he was almost here. Just adding that so you know I'm not anti-pain relief for childbirth at all - if I'd needed it, I'd have used it!

**I still feel very lucky that everything went 100% right and I didn't need it. I know that's not everyone's experience.
posted by annathea at 11:48 AM on December 20, 2012 [2 favorites]

People with certain forms, or polymorphisms, of the liver enzyme CYP2D6 can have difficulty metabolizing codeine, dextromethorphan, and other morphine precursors and therefore do not effectively respond to some opioid painkillers (see this review). CYP2D6 polymorphism is seen in up to 10% of the population. Genetic testing for CYP2D6 polymorphism is conducted in some cancer care centers, such as the Mayo Clinic, but is not routine.
posted by Dr. Regardless at 12:10 PM on December 20, 2012 [1 favorite]

I guess it is ultimately a pretty stupid nomenclatural difference, but its one that could be important for guiding google searches. What you are talking about, the lack of efficacy of opiates for a variety of kinds of pain for you, would in the most proper sense be described as you having a low sensitivity to the opiates. If you had a specific kind of pain that opiates were not working for, even if opiates worked for you in general, that pain would be described as having a resistance to opiates.

The effect is what is important to you right? Pain is an awfully subtle thing, made only more subtle by all the reasons why placebos and importantly to you nocebos work, that is very much influenced by things like one's state of mind and expectations. Different opiates do have different mechanisms of action and there are strategies of pain management that do not include opiates, you may not necessarily have a reduced sensitivity to all of them. This is really a question for either your midwife if they are equipped or the medical staff behind them.
posted by Blasdelb at 12:20 PM on December 20, 2012

Apologies, I don't think I was very clear before -- there are a number of different CYP2D6 polymorphisms that can have a variety of activities from over-metabolism to no drug metabolism at all. I was referring to the ~10% of the population that may lack CYP2D6 entirely. From the review I linked to above:

"A lack of CYP2D6 enzyme results in reduced effectiveness of drug therapy in instances where prodrugs requiring activation by CYP2D6 are used. This is seen for the analgesic effect of tramadol and codeine."

CYP2D6 is also required to metabolize the cancer drug tamoxifen -- hence the testing at cancer care centers. Psychiatric drug response genetic testing for CYP2D6 and another metabolic enzyme CYP2D19 is part of the growing trend of personalized medicine.
posted by Dr. Regardless at 12:26 PM on December 20, 2012

I'm a labor and delivery nurse, and I work at a hospital that has a well-earned reputation as a supporter of non-interventive, unmedicated birth. We welcome doulas, most of our births are attended by midwives, and you'll never EVER hear anyone say that things are "taking too long" or that we need to "hurry it up a little." Many of our patient successfully use hypnobirthing techniques to manage their pain. Our epidural rate is the lowest in the state, at about 25%. (I say all of these things to provide some evidence that I know of what I speak when I talk about unmedicated birth.)

Others have already answered your questions about potential reasons why you respond differently to opiates, so I won't add to that, but I want to lend a little perspective about unmedicated birth.


Second: spend as much time in the water as possible. Warm shower, tub, whatever you have access to.

Third: the most uncomfortable place to be is immobilized in a bed. Provided everything is progressing normally, you should spend every moment you're not being monitored upright (walking or sitting on a birth ball) and/or moving. It will still hurt, but it'll hurt a lot less if you're in motion.

Fourth: Many women in my care who've received fentanyl have told me that they felt groggy, dizzy, and disconnected due to the medication, but not really in any less pain. Injected narcotics are sometimes useful and sometimes not. There's no guarantee that you would benefit from them even if you were a normal metabolizer of opiods.

I would also like to say that this:

injected narcotics for pain relief pose fewer possible complications and interference with labor than an epidural

is not a useful statement. It could or could not be true for your specific birth. It is most certainly not true for every birth.

Birth is unpredictable. You will have little control over some parts of it, and active labor is not the time to try to make peace with that idea. The unhappiest labors I've seen were with women who tried to control the uncontrollable parts and became so consumed in the struggle that they missed out on the joy of the experience.
posted by jesourie at 1:22 PM on December 20, 2012 [5 favorites]

No red hair in my family, although that is an interesting link.

FWIW, I'm Asian, no red hair at all, and I've never found an opiate that worked for me. Also, labor literally felt like I was being ripped in two. Apparently, I had an "inflexible cervix," according to my midwife. I too had planned on an unmedicated birth, but stuff happens, and I'm glad I gave myself permission to do whatever was necessary for a safe delivery
posted by snickerdoodle at 4:15 PM on December 20, 2012

oh my, I can't believe I forgot to mention hypnobirthing techniques.

Um, yes, I gave a lot of credit to the water in my post above. But I also used the hell out of Hypnobabies tracks. And look, there are a lot of rules about Hypnobabies and how to use it during pregnancy for maximum efficacy during labour but let me just say that I could not stand the sound of that woman's voice when I was pregnant - either time! - and when I was in active labour you could not part me from my headphones and iPod for love nor money. I took her in the tub with me, I carried her as I paced, I did not let go of those hypnosis tracks.

I don't know why they helped even tho I listened to them in my own order and refused to listen to them while pregnant. I do have some experience with self-hypnosis (I used to listen to my mom's smoking-cessation hypnosis tapes as a kid to help with insomnia. Coincidentally, I'm not a cigarette smoker. Hm) so I might have been able to use that experience to skip the "practice sessions".

Anyway. Hypnobabies was totally worth it for me. I don't know if it helped with pain but it helped me get in the right place to focus where I needed to focus.
posted by annathea at 7:40 PM on December 20, 2012

I'm a doctor and a lot of my job is dealing with acute pain.

Codeine is a drug that is not easily metabolized by all people. I'm not sure if the above poster who referred to this (the "CYP2D6 polymorphism" thing) put it in terms that could be understood by a layman, so let me repeat: something like 5-10% of Caucasians (and some of other races) have a genetic variation that means that they don't metabolize codeine well. This doesn't seem to be such a problem for hydrocodone, but still, there are plenty of people that feel that oxycodone works better for them than hydrocodone, or vice versa, depending on that person's body's reaction to the drug. Because of the issue with codeine specifically, I never prescribe it as an analgesic at all, unless the patient specifically tells me it has worked well for them before. I only use it as a cough medication.

The variable response to pain medication is a VERY well known phenomenon, so much so that I usually ask every patient "has there ever been a pain medication that didn't work well for you, or that you had a problem with" prior to prescribing any opiate medicine - even if they have no allergies, tons of people have subjectively different experiences with different medications.

Rest assured, however in two things:
1. Fentanyl is processed by a different bit of the liver than hydrocodone and codeine are, so your reaction to these medications may be quite different.
2. I've seen thousands and thousands of patients and I've never come across anyone who's resistant to all opioid drugs. Plenty of people with a variety of allergies or bad side effects with opioids, but completely resistant, no, that would be extremely rare. You've had some of the least potent narcotic drugs and probably taken the lowest possible doses of them, as you should. I can essentially promise you that were someone to load you up enough with narcotics, you'd be snowed. That is not how you should be hoping to undergo childbirth, but I just mention it because it's nearly universal as a human response if you get a high enough dose of these medications, and I don't want you to be afraid that if you have severe pain on another occasion someday it'll be untreatable.

On a side note, many people have unrealistic expectations of pain medications that can affect their perception of using them. I guess we doctors should take it as a compliment, but there seem to be some people who believe that we should be able to take away their pain completely, no matter how severe it is. They then become quite disappointed to find that pain medications only *decrease* their pain level and make them more comfortable, rather than completely removing their pain. I've seen this phenomenon in women in labor as well, after getting an epidural. They freak out and yell "I can still feel it!" - guess what, yes, you can. Unless you're under general anesthesia, you're not going to be completely pain-free, because you will be conscious. Be prepared for that and be prepared to work through whatever you do feel, while your medical providers try to get you as comfortable as they are able. Best of luck! I'm in the 3rd tri myself and totally understand the terror thing.
posted by treehorn+bunny at 7:55 PM on December 20, 2012 [3 favorites]

I was given two doses of fentanyl when my son was born a few months ago. Each lasted about 20 minutes. I don't remember this part at all, mostly because I hadn't slept in days and was in some sort of altered state already. From what I was told, it allowed me to sleep for a bit.

As treehorn+bunny said, I think I assumed that pain management in childbirth was very binary: an unmedicated birth (as I'd planned) would be painful in that good-but-challenging way, and a medicated birth would allow my baby to float from my body on painless clouds, but might be risky for him and therefore I wouldn't attempt it.

As it happened, I was induced after about 30 hours, and at that point was concerned I did not have the strength to go through delivery without some rest. Fentanyl gave me a brief break, but ultimately I had an epidural, and then slept a little bit during the next 15 hours while dilating. By the time I was ready to push, the epidural had been turned way down, and I had two hours of the most excruciating pain I've ever experienced. And yes, it's a different kind of pain than trauma pain. But it is extraordinary, in every way. Even medicated.

I guess I would add this: there is no way not to be concerned about this beforehand, and of course you want to try to "know" what will happen as much as you possibly can. I read a million books and asked everyone I knew about their birth stories and documented my birth plan, etc. In the end, it is unknowable. And finite. You endure what you can endure during that process, and you get the help you need to get through it, and you get this amazingness on the other side, mostly, if you're lucky.
posted by judith at 8:42 AM on December 24, 2012 [2 favorites]

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