Efficacy of codeine vs. methadone

Factual Questions
21

Opiate neuropharmacology is incredibly complex, as shagnasty and others have already pointed out. I actually studied it for a few months under Sol Snyder, the Guru of Opiates, years ago and learned a bit. And it’s gotten more complex since then!

Basically, you got your kappa, lambda, and mu opiate receptors. Each opiate molecule has different affinities for these receptors, and one type may block one type of receptor while activating another, while ignoring the third, or some other permutation. Effect of the drug varies depending on what it’s doing simultaneously at each receptor site, how long it’s bonded there, and whether or not it’s bonded strongly enough to prevent other opiates from bonding there.

Then you got your opiates which need to be metabolized before they cross the blood-brain barrier, or after they cross, or both, or neither. You have some that cross the barrier in seconds, others may take hours.

Then there’s the opiates that are active as euphoric drugs and pain relievers in their primary form, that get metabolized slowly to another form where they may be more potent, less potent, or even antagonistic to the euphoria and/or the pain response.

Then you have to figure out the route of the drug: Taken in pill or liquid form by mouth, injected into a muscle, injected into a vein, injected just under the skin, inserted rectally, absorbed thru the skin in patch form, or even inhaled, snorted, or used as eye drops. Also injected directly into the central nervous system via a catheter either into or just outside of the spinal canal sac, or infused directly into one of the ventricles of the brain.

Then you should take into account other unrelated drugs that may be in the system at the same time which may either potentiate or diminish the pain-relieving effects of the drug, such as antihistamines, benzodiazepines, stimulants, etc.

All those equivalency tables regarding comparable pain-relieving doses are some rough guidelines based on very subjective reporting by a few handfuls of test patients. Useful as a rough guide in general, but not to be relied on real strongly in any individual situation.

There’s still a lot to be learned. I always remember that heroin was originally designed and marketed to be a non-addicting substitute for morphine, a good pain relieve but a horrible scourge for the addicted and their families. That didn’t pan out. Then demerol was pitched the same way, and look what happened. The same for the mixed agonists/antagonist drugs like talwin (remember T’s and blues, the poor man’s heroin?), stadol, and nubain. And lately, tramadol (ultram) was pushed as a safe alternative to narcotic pain killers. Well, it ain’t.

22

I side with Shagnasty and picunurse here. At the simplest, it is really just basic chemistry. Grams is a very bad way to dose drugs, we should really be doing things in moles. If we compared in molar dose, then we could really compare the molecule-to-molecule efficacy of a drug. For instance, in your OP, let’s say a molecule of methadone weighs 50 times more than a molecule of codeine. So 30 mg of methadone would be 50 times less of a dose than 30 mg of codeine, as there would be 50 times less molecules to bind to 50 times fewer receptors. So just comparing the gram-to-gram of two different meds doesn’t tell you jack squat. Now methadone doesn’t weigh 50 times more than codeine, in fact IIRC it is a much smaller non-opiod ring containing opiod. But the point remains.

There are hundreds of confounding factors. As Shagnasty mentioned, there is the whole bit with receptor binding. There’s half life. There’s therapeutic indicies. There’s volumes of distribution. It goes on and on. So dosing things in moles, or in mg/kg like in pediatrics or in mg/m[sup]2[/sup] like in chemotherapy or whatever gets you a little less confusion but doesn’t solve your problem.

In the end, there is a handy-dandy number that gets attached to opiods (moreso than any other class of medications), by which someone has made an educated guess based on all the factors (and usually the physiology like respiratory depression and subjective pain reporting of patients on the end) where they say opiod X = 30 times morphine. Or fentanyl is equal to 80 times morphine or whatever. It allows conversion between different pain meds, which is very useful. People don’t do this with antibiotics, or antidiarrheals, or benzodiazepines or whatever. I may have heard it with some NSAIDs (there’s one somewhere for Toradol versus ibuprofen that I heard at one point), but it is mostly with opiods.

23

Yes, they are different but saying they are fundamentally different is a travesty of the language. Heroin and LSD are ‘fundamentally’ different.

24

** QtM** since the OP was about methadone maintenance I gave the doasge regime for that. For pain it is 5-10mg every 6-8 hours, in prolonged use not more than every12 hours, right?

psychonaut- the urine is tested two ways, firstly with a standard drug reagent card, which has windows for all the drugs I mentioned (i.e. LSD is on the card, it’s not a separate test). Secondly the urine undergoes a more sophisticated test (sorry, can’t remember what, it might involve chromatography) which can differentiate between the different opiates and opioids, so that they can tell if the patient is just taking their methadone or “topping up” with codeine, heroin, oxycodone etc.

25

Gas chromotography - that’s what they use for the most sensitive testing.

Irishgirl gave a description of methadone maintenance where she is - when I was working at a clinic in Chicago we had a few differences. For instance, our long-term patients could earn the privilege of taking away a two-week supply, and visited only twice a month. We regarded any illicit drug showing up in the urine as a “dirty”. There were enormous legal/social pressures to get people weaned off methadone, and to do it as quickly as possible - which I don’t think was always wise. Our “clients” were enormously variable and some really did need more time and attention than others. While it might ideal to get everything totally clean and sober the reality is that can take a long time for some folks, and the notion of “harm reduction” has a lot of merit.

We saw enomrous variability in dosage for the addicts. Little teeny women on 200 mg a day, big huge guys on 30 mg. Like I said, the people varied enormously.

26

I always thought that heroin was originally marketed as an antitussive. I used to have a facsimile of an advertisement from the 1890s touting it as the latest and greatest cough remedy for adults and children.

27

Most opiates are strong anti-tussives. And heroin was marketed that way too. But it was developed for it’s pain-killing properties.

28

That is certainly one commonly used and relatively effective regimen.