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Why Can’t We Make Better Painkillers?
I asked this question on Fred’s post about the problems his family’s had filling his mom’s prescriptions for painkillers — medication she needs to treat the pain of advanced lung cancer. Moments after asking it, I began thinking, “Hey, wait — that’s a good question.”
Or maybe it isn’t, but I figured there could be no harm asking, because I bet I’m not the only one to wonder.
Why is it that the only really effective painkillers we seem to have are highly addictive and dangerous drugs that addicts love? The point of a painkiller is to make the pain go away, not to get you high, so why do we not yet have a class of drugs that only do the former? Or, to wit: We already do have many of them, such as aspirin, acetaminophen, and ibuprofen. And those are great, effective drugs, as anyone who’s had a headache or a sprained ankle knows. But apparently, they’re not effective enough to treat more serious pain.
So for those of you who know more about medicine, pain management, and drug development than I do: What’s the problem?
It seems to me that the long-term solution to the problem Fred and his family are confronting — one my family has also confronted, and I’ll vouch for the horror of trying to secure effective painkillers for a terminally ill relative and being treated like a common drug addict for doing so — is to create a better class of painkillers. We clearly need painkillers that treat pain but are of no special interest to people who want to get high.
In other words, isn’t this a medical research problem?
Can anyone here shed any light on the obstacles to creating that kind of drug? Is anyone close to doing it? Are any such drugs in testing? If not, who’s doing the most interesting research into the problem?
It seems to me the market for such drugs must be absolutely massive — if we consider “pain” a disease, it’s one we will all, almost certainly, face sooner or later. And short of dementia, I’d guess it’s also the one most of us most fear. Most of us would pay almost any amount of money not to experience terrible pain, or worse still, see a loved one in excruciating pain. So I can’t imagine there are no financial incentives to drug development: an orphan disease, this is not.
An effective painkiller that posed no risk of mental impairment or addiction would be (I would think) one of the most profitable drugs ever manufactured. It would leave Viagra in the dust. It would inherently be an obvious social boon, with a very significant secondary social benefit: There would be no reason strictly to control or limit its prescription.
Why is this problem so difficult, medically? Is the obstacle a known and thus-far insoluble medical one? Or is it a political, regulatory, or economic problem? Is it somehow related to the drug development process?
Does anyone here know?
As I was writing this, another question occurred to me. What would be the obstacle to creating drugs that get people as high as the opiate painkillers do — if that’s what they want to be — but that don’t impair mental functioning and judgment, and aren’t as likely to kill them if they overdose? Why, in other words, aren’t we fighting a war for drugs — much better ones?
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Aha! You need hypnosis! You are feeling relaxed, very relaxed. Your arms are heavy, your legs are heavy, you are sinking, sinking, sinking . . . . .
RE: #84 – No problem with patience, Claire. I only work in anesthesia one day a week and I like it much more than when it was 50 – 60 hours. The rest of the time I try to satisfy my intellectual curiosity (and not be driven insane by the politics/culture in the US).
Much new genetic information is becoming available and we are headed toward “individualized medicine,” where we will know a priori which patients will respond best to which medicine. This has the potential to offer better results at reduced cost. One example: when ondansetron (anti-nausea) became available it was $25 per dose. It was quite effective in one patient out of five. So the NNT (number needed to treat) was 5. It took $125 to help one patient. And this is a drug with minimal side-effects. Apply this principle to chemotherapy, for example, where cost is very high and a significant number of patients do not benefit yet still have complications, and you get a sense of the potential cost and patient benefit from knowing who to treat with what based upon their genomes, in advance.
I indicated previously that variations in opioid receptor genes have been discovered (called gene pleomorphism). This may well account for the wide range of tolerance seen in patients given narcotics. (Con’t – running out of words)
Patients respond differently not only to a given dose, but to different drugs. A given patient of the same age, weight, surgery, etc. may require two to 3 times the dose of another similar (in all apparent ways) patient for adequate pain relief. Add to this the fact that those who have abused opioids in the past may require even higher doses than those (and such tolerance remains even after years of documented abstinence). Actually, in my experience, the only patients who tell me they were addicted are those who are in recovery programs and are abstinent.
In recovery room, some patients get little or no relief with morphine given IV (so there is no issue of bioavailability, as can be the case with oral meds). I then switch to hydromorphone (Dilaudid). Occasionally, as third-line, I use meperidine (Demerol or pethidine in the UK). Then, the nausea profile of a given drug can become a factor, in the same unpredictable way as potency of pain relief. In short, opioid administration is highly empirical.
In an ideal world, every patient’s opioid choice, dose, and dosing interval would be individualized and adjusted after the first doses, but staffing such an ideal would be cost-prohibitive. PCA is a compromise, where standard doses are ordered, usually erring on the safe side, so doses are often lower than those which would offer better pain relief to more patients. (con’t)
As to adverse health and healing effects of opioids, there is a wide range of opinion among physicians. A few don’t pay much attention to patients’ pain. As a hammer, so to speak, I tend to see pain as a nail. Earlier, someone mentioned “no free lunch,” and alas there are not many of these in medicine. General anesthesia and heavy sedation have some adverse effect on immune function and, in some patients for some operations, on cognitive function. So do blood transfusions. Like much of life we discuss on Ricochet, most medical decisions involve trade-offs (severe pain vs. marginal reduction in rate of healing/recovery, practical compromises (like standard doses of PCA). The desire to figure it all out, I understand. I have only limited knowledge of things I deal with all the time. What I don’t understand is (if I am correctly reading between the lines of some comments) resentment that medicine (like all of life) is imperfect – despite extraordinary care and effort of most doctors, nurses, and other healthcare workers.
Civ,
Might this be an explanation for some of the incoherent policy choices made on pain-relief. The oversight is cost prohibitive. Now with an inefficient system like the ACA bogging everybody down won’t that get worse?
What do Doctors do? They diagnose. People think that means they look at you once and then they know everything and bang zoom you’re treatment regime is fixed. The reality is that many mid-course corrections of the treatment regime must be performed for most patients most of the time. That’s expensive unless you are super organized. I think smart phone/internet technology could help on the follow-up but it still needs a lot of brains looking at the data on the physician side. That’s expensive no matter what you do. It’s amazing to me that BHO and company could have conceived of anything as sweeping as the ACA without a massive program to produce more Doctors. Incredibly stupid. Prices will continue to rise and the quality of care will get worse.
Regards,
Jim
Actually, I think only the quality will decrease, because the ACA is price-fixing from top to bottom. More and more physician decision making is by algorithm, dictated by government. Hospitals will be starved for money by low payments and (much-overlooked, so far) unaffordable deductibles. From painful experience, I can say that patients simply do not pay their out-of-pocket medical bills. Many, if not most ACA policies have $5K deductibles. Unless hospitals collect it up front, they will never see it and hospital margins are very thin. There will be bankruptcies and overworked/demoralized staffs of doctors and nurses.
Claire & Civ,
I’ve told people a hundred times if you want to know about the ACA just talk to the Doctors. Most of the ones I talk to voted for Obama. Every single one has their own horror stories about the ACA.
The thing needs to be thrown out and the simple but effective approach laid out by Rubio-Walker-Jindel plans should be implemented. It’s not an ideal world and it won’t be tomorrow. If we could institute basic simple clean reforms we could make it better tomorrow. Or we can just give in to the ACA and sit back and watch the disaster unfold.
Regards,
Jim
Care and effort doesn’t absolve responsibility, in medicine or in any other part of life. We expect higher standards from doctors, that’s why they’re held in such high regard.
But a discussion of the problems with medicine as currently practiced is way outside the scope of this thread!
Thanks for taking the time to provide answers from a practitioner’s point of view. I hadn’t realized the wide variation in responses to opiates, for instance.
Given the lack of human genetic variation compared to other species, it really is remarkable what a wide range of outputs we see.
I’d rather take longer to get better and not feel like horse[expletive].
They did one study they had to halt because the mortality was much higher in the intensive fever treatment wing. The standard care wing, in other words.
But yeah, most of the time you just feel lousy. It’s not that big of a deal.