Different for everyone. It knocks me right out. I guess that means no pain. 
This is a good layman’s intro to pain management vs the various opioid and non-opioid drugs out there. Noting that those two broad categories each contain lots of meds, but the two categories each work very differently on different chemical pathways within the body. And the non-opioids in turn can be subdivided into several additional functional classes based on their chemical activity in the body.
Just cherry picking a couple of entries, and ignoring a few details, Tramadol is about 1/10th strength morphine while Fentanyl is about 100x strength morphine.
Now THAT is an incredibly complex topic. Explaining morphine and heroin is frankly a lot easier.
Tramadol is active at the mu opioid receptors in the human body and is also a serotonin-norepinephrine reuptake inhibitor (SNRI). So it can reduce pain and also reduce symptoms of depression, neuropathy, social anxiety, fibromyalgia, and more. BUT its effects vary greatly from individual to individual, particularly if an individual has CYP2D6 mutations which make tramadol pretty ineffective for pain relief.
It works well for a lot of folks, but can cause problems, particularly in that abrupt discontinuation after prolonged high dose use can result in both opioid and SNRI withdrawal, which can be life-threatening.
Lots more could be said here, but it’s time to make dinner. I’m off to the kitchen.
True. But there are guidelines on how to justify the use/availability of “fixed combination medicinal products” (that’s the European term - what follows is taken from European guidance rather than the US guidance, simply because I’m European and that’s what I’m familiar with. That said, I would be surprised if US guidance was materially different.)
From: Guideline on clinical development of fixed combination medicinal products
Applicants are required to justify the pharmacological and medical rationale for the particular combination of active substances within the fixed combination medicinal product and for the intended therapeutic indication.… Part of the rationale for fixed combination medicinal products may be to optimise the use of the medicine in terms of (number of) doses administered and patient adherence, or to help prescribers optimise and/or implement treatment where use of multiple active substances is indicated. Such simplification of therapy is, however, insufficient by itself for a complete justification of a fixed combination medicinal product. The combined use of the active substances is expected to improve the benefit/risk by increasing efficacy and/or improving safety in comparison to the use of (any of) the single active substance(s).…. For any fixed combination medicinal product, it is necessary to assess the potential clinical advantages of combination therapy against the use of monotherapies, in order to determine whether the product meets the requirements with respect to efficacy and safety. It should be justified that the advantages of combination therapy outweigh its inherent potential disadvantages such as addition or strengthening of adverse effects, and the fact that fixed combination medicinal products may not always be easily adjusted to the need of individual patients.
I cut that slightly with an eye to fair use. For the full version (and much more besides) see this guidance document (PDF WARNING) . That section is on page 4 under the sub-heading Rationale.
Similar similar acetaminophen-opiate combination products are (unsurprisingly) licensed in Europe.
j
This mnemonic reminds me of the Woody Allen movie Annie Hall.
Joey Nichols thinks that the fact his name is a homonym with “nickels” ought to blow any kid’s mind. “Nichols! You see? Nickels!” he bellows, slapping a nickel on his forehead. “You can always remember my name, just think of Joey Five Cents! That’s me! Joey Five Cents!”
All that is well and good and rational, but my own ‘from the trenches’ experience caring for patients is that I saw a lot of harm done (including some fatal outcomes) over decades to addicts who took too much APAP in order to get enough opioid in them to prevent withdrawal or give them a sufficient high.
Admittedly I never studied the data to determine if the number of patients whose pain was relieved better by the combination justified the number who would suffer morbidity and mortality from that same combination.
Of course, I absolutely defer to your real world experience; I just thought it was worthwhile posting an example of the regulatory rationale behind combination products. It can be quite a controversial area - combi inhalers are a good example of that.
j
I agree, thanks for doing that. I find some combination inhalers very logical and helpful, some much less so.