Narcotics stronger than dilaudid/fentynal

Mrs. Hell has been quite ill for the past few years and has recently been diagnosed with primary sclerosing cholangitis. The strictures in her biliary tree are quite painful as are other side effects of her illness (like the hematoma in her liver that the biopsy gave her). To make things worse, she had cancer twice when she was a child and because of the pain management related to that, she is quite resistant to narcotics.

She’s worried now because her pain medication isn’t working so well and we may need to switch to another drug. Right now she is on Fentanyl 100micrograms patches every three days and 4mg dilaudid every three hours as maintenance and another 4mg for breakthrough.

What medicines would likely be prescribed when these don’t work anymore? Her pain management doc seems somewhat medically competent, but his office is staffed by morons. They don’t deliver messages, answer the phone, etc. Of course, he’s on vacation this week, so the teeming millions may well give an answer quicker.

This isn’t an actual request for medical advice. Just a general question regarding options for treatment of a patient who has an extremely painful condition and who is highly resistant to narcotic painkillers.

Thanks in advance,

One of the difficulties with opioids is increasing tolerance; another is that in some patients they just don’t work very well.

It isn’t always the case that opioids are automatically the “strongest” pain medication. Some conditions or patients might respond better to NSAIDS, for example.

It sounds as if she is already in the hands of a physician specializing in pain management, and that’s a good start. I would not hesitate to mention staff failures to the physician when you see him.

Beyond that, in a patient for whom Fentanyl does not provide relief, I am not expert enough to suggest alternatives. It is the case that sometimes one narcotic will work better than another in a given patient, but if your wife has a long history of chronic pain, it’s likely she has already tried most options.

Has a chart - subjective of course. I always kind of thought the “opioids aren’t always the best” was bs until earlier this year. I had though I slipped a disc (turned out it was just a pulled muscle). It was the worst back pain I had ever felt. I had some oxycodone and took plenty of that. Went to the doctor expecting more narcotics and was kind of ticked off when I got Celebrex instead. The Celebrex worked. The oxycodone made me feel “good”, but was still in awful pain. I couldn’t feel the Celebrex working, but there was no pain - almost zero after a couple hours. After a few days it went away (just as my doc said it would).

A couple months later I felt what I thought was the exact same pain. I thought great - going to use this Celebrex. This time the Celebrex didn’t do anything - while the Oxycodone did.

I am truly sorry about your wife’s pain. I too am a chronic pain sufferer and have been on more opioids than I can count. I was using Fentynal for about two years but I was very concerned about my ever increasing tolerance. I also had issues with the patch, things like inconsistent dosing (sometimes the patch seemed to run empty a day early, leaving me in horrible pain), plus I was always worried a patch might fall off me and come in contact with another family member (a potentially fatal event).

I finally found a doctor who shared my concerns and switched me to daily use of extended release morphine, boosted with percocet for breakthrough pain. The morphine works well and is much more predictable than the Fentynal patch. But, as with the patch I find my tolerance building with each passing year. I am only 46 and I worry that my tolerance will be so high by the time I hit 65 that nothing will work. A very scary thought. I have been told there is no maximum dosage of opioids, the max dose being dependent on a persons tolerance. However the amount isn’t an unlimited one. Eventually a person will stop breathing if the dose gets too high.

I raised this concern with my previous doctor and she told me that when the Fentynal stopped being effective that she would switch me to methadone. I can’t tell you if this is appropriate or not, but it is what I was advised as to the next level of pain control when traditional opioids were no longer effective. Pain is a bitch isn’t it?

Even thought the OP may not be asking for actual medical advice about a real-life situation, this one is better in IMHO, so that posters who only play doctors on the internet can chime in.

samclem, moderator

Is there any explanation for why opioids don’t work very well on some people, other than building resistance? When I was in Americorps in 2009, every time I went to the doctor they would feed me hydrocodone like it was candy. I didn’t respond much to them – taking aspirin worked about as well for me.

However, back several years ago when I had back pain from a car accident that sent me to the ER, the doctor shot me up with something – I never asked what it was – and the pain faded out so quickly that I was sobbing with joy. It was amazing. No idea what it was, though.


So there is this family of enzymes, mostly living in your liver, that are responsible for metabolizing most of the drugs prescribed. These are the CYP450 enzymes. This family has lots of enzymes which go by similar names (CYP2D6, CYP2C19, CYP3A4, etc.), each of which takes primary responsibility for metabolizing a drug or group of drugs.

As with most things, there are different polymorphisms of each of these enzymes. One polymorphism (one type) might be a really active, efficient enzyme, while another polymorphism might be really slow and not very effective at all. A third polymorphism might be somewhere in between. Everybody gets two different versions of each enzyme (one from mom, one from dad) and these combine to give each person a general level of enzyme activity. If you got two fast versions, you might be REALLY quick at metabolizing drugs worked on by that enzyme, but if you got two slow versions, the drug might stay around in your system forever while your sluggish enzymes tried to decide whether to metabolize them or not.

This is all well and good, but not the complete story. These CYP450 enzymes metabolize drugs that you ingest. “Metabolize” can mean activate or inactivate, depending on what kind of drug you are talking about (some drugs are packaged as pro-drugs, which need to be activated by enzymes before they work, while other drugs are active right out of the bottle, and are metabolized into inactive metabolites.)

The clinical significance of all this is, that people will have different responses to different drugs, depending on what kind of drug it is (pro-drug or active) and depending on the genetic make-up of the metabolizing enzymes.

For example, codeine is packaged as a pro-drug, that needs to be turned into morphine by CYP2D6. For people who are slow metabolizers with CYP2D6, they get ineffective pain relief with codeine, because they never actually convert it to the active drug and it just gets excreted unused. For people who are ultra-fast metabolizers, on the other hand, they can get codeine intoxication, because their liver is too enthusiastic about converting codeine into morphine.

All of this gets even more complicated when you start throwing in other things that can induce or inhibit these enzymes. SSRIs inhibit CYP2D6 (the enzyme that activates codeine). So if you are a slow metabolizer already, and happen to be taking an SSRI, you will be even more slow. Each enzyme has a list of things (other drugs, grapefruit juice, alcohol, herbal supplements) that inhibit OR induce it.
So, yeah. TLDR: genetics.


I have been on al diferent types of narcotics in the past and when they start to loose their strength I turned to the needle with Dilaudid pills. That got the job done. Shooting them can be very addicting but whatever you are already addicted to the pills. Shooting them requires you to take less and they are way more potent. I would only recommend this with Dilaudid though and thoroughly research how. An intramuscular shot is better than taking them orally; however, intravenously will give you the most pleasure and pain relief. The way I see it they do it in the hospital so why can’t I do it myself. Diabetics use needles to shoot up their insulin so whats the difference if you are doing it for pain relief.

It was most likely Dilaudid