Tapentadol is a drug for pain. It was approved by the US FDA for the treatment of moderate to severe pain. The FDA news release was dated 24 November 2008, although the actual approval was a few days earlier.
Tapentadol acts on μ-opioid receptors, making it similar to morphine and its ilk. Do we need another opioid agonist? And if so, why? Suspicions deepen because it was produced by the same company that makes tramadol, hydrocodone dxt. Indeed, it is similar to tramadol in many ways. Tramadol is the active ingredient in Ultram®, now available as a generic. This is sounding like a familiar me-too drug story.
On the other hand, hydrocodone dxt, chronic pain is a common problem:
Chronic pain prevalence estimates were 10.1% for back pain, 7.1% for pain in the legs/feet, 4.1% for pain in the arms/hands, and 3.5% for headache. Chronic regional and widespread pain were reported by 11.0% and 3.6% of respondents, paracetamola and tramadol, respectively.
Existing treatments often are not satisfactory. With opioid medications, there is risk of psychological dependence and various kinds of diversion and misuse. People put it in their noses and veins and things like that. Perhaps more importantly, though, is the fact that some people develop adverse effects at the doses required to achieve adequate pain control, hydrocodone dxt.
So what makes tapentadol different?
Much of the information presented here comes from this article:
(-)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol Hydrochloride (Tapentadol HCl): a Novel µ-Opioid Receptor Agonist/Norepinephrine Reuptake Inhibitor with Broad-Spectrum Analgesic Properties
First, let's look at tramadol, paracetamola and tramadol. Tramadol is an agonist for μ-opioid receptors, but it also inhibits reuptake of serotonin and norepinephrine (monoamines). It appears that the effect on monoamines is something that is important for the analgesic effect of tramadol. After all, tramadol hydrochloride dogs urination, tramadol is a rather weak agonist of opioid receptors.
Tramadol, however, has several problems. The weakness of its effect on opioid receptors means that it would not be expected to have a robust effect on acute pain. The fact that tramadol depends upon the monoamine effect for its action, means that it often works better for chronic pain, hydrocodone dxt. (Note that the use of weasel words, e.g. "expected," "often" is intentional; ; it reflects the fact that different people respond differently.)
Furthermore, tramadol by itself is not very effective unless some of it is metabolized to O-desmethyl-tramadol. This requires an enzyme, cytochrome P450 2D6 (CYP2D6), tramadol kiespijn. Persons who are relatively deficient in CYP2D6 activity, or who are also taking a drug that blocks CYP2D6, may not get the full effect.
Lastly, tramadol is a racemic mixture; that is, hydrocodone dxt, it comes in left- and right-handed versions. The actions of the two versions are different, and the actions of the two versions of the metabolite are different. This is not necessarily a problem, but it is a complicating factor.
With the understand on tramadol, we now can take a look at tapentadol to see if it offers any meaningful advantage.
The key differences are: tapentadol has a stronger effect on the reuptake of norepinephrine than serotonin, it does not depend on CYP2D6 activity, and it is not a racemic mixture. All of these factors are advantageous, at least theoretically. Based upon these findings, one would expect that tapentadol would be less prone to cause adverse effects, buy generic ultram buy cheap online uk ultram, and that it would be much less likely to be involved in drug interactions. Premarketing data are encouraging, though.
Additionally, tapentadol is more potent than tramadol at the μ-opioid receptor, paracetamola and tramadol, but less potent than morphine, hydrocodone dxt. Note, however, that higher potency does not necessarily translate into higher clinical utility.
I tend to think that the advantages are great enough to justify the development of tapentadol for the market, tramadol hydrochloride dogs urination. There are so caveats, however, buy generic ultram buy cheap online uk ultram. It is not possible to make any firm assessment of a risks of a drug, prior to its release into the wider market. That is, the basic pharmacology suggests that most patients will be less likely to have adverse effects, but this remains to be seen.
Also, as is the case with any opioid agonist, the potential for diversion and abuse cannot be assessed fully, tramadol hydrochloride dogs urination. There are examples of drugs that were thought to present a minimal risk of abuse, hydrocodone dxt, prior to being released into the wild, but for which that turned out not to be the case. Talwin, Stadol, and of course Oxycontin, paracetamola and tramadol, come to mind in this respect. Iwould be very cautious about making any assumptions about the potential for diversion and abuse with tapentadol. In fact, the DEA has yet to assign the drug into one of its schedules.
As for what I think of tapentadol, I suspect that it will turn out to be useful, but not a blockbuster, buy generic ultram buy cheap online uk ultram. If the safety profile is significantly better than that for tramadol, it may be possible to use it at higher doses, which might translate into greater clinical utility.
I do have two big questions, though, hydrocodone dxt. One: is this drug really any better than a combination of a medium-strength opioid, say hydrocodone, along with a norepinephrine reuptake inhibitor, say nortriptyline? Both are pretty inexpensive, so for the tapentadol to have a rational place in our pharmacopoeia, it would have to have some benefit that cannot be gotten for less money, tramadol kiespijn. (Not that markets are always rational, but still...)
Two: what it is potential for lowering the seizure threshold? Tramadol does this. It usually is not an issue unless a person takes a great deal more than what was prescribed, or it there is a drug interaction. The drug interaction should not be a problem with tapentadol, but we can assume that many persons will take doses that are larger than prescribed, hydrocodone dxt. Tapentadol presumably will come with a warning about that, but that won't stop many people. Note that I do not consider this a reason to keep the drug off the market, but I do think that clinicians should keep the possibility in mind.
_________
Disclosure: I don't own any pharmaceutical stocks (not directly, anyway; I probably have some small bit in a mutual fund somewhere), tramadol hcl and dog, nor do I work for any company that has anything to do with any of the products mentioned.
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