Methadone has a quirk in metabolism. The pain receptor effects wear off before the drug is cleared from the body.
So dosing may be ordered too frequently and hence the other potentially dangerous effects become more likely.
http://findarticles.com/p/articles/m.../ai_n29445367/
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Despite methadone's attractiveness for the treatment of pain, it's a complicated drug to prescribe. Methadone is difficult to does and equianalgesia is a particular problem, because the analgesic and biologic half-lives don't match. While the biologic half-life of methadone can range from 18 to almost 100 hours (average, about 24 hours), the analgesic half-life ranges from 6 to 12 hours. "So the steady state of methadone--because of its long half life--can take a while to reach," Dr. Gazelle said. Reaching a steady state takes about five biologic half-lives, she said....Other medications, including azole antifungal agents and macrolide antibiotics, might inhibit the cytochrome P450 system and require decreased doses of methadone. Therefore, it is important to review all of the medications that a patient is taking before prescribing methadone.
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In practice this is what I see... Doctors do not understand the liver enzyme systems and often do not refer to charts which list which drugs affect which subsystem of the P-450 complex in the liver. Add to that that genetically there are people with errors in this system, which make them "slow metabolizers". For example when the statin drug for cholesterol ..the very potent Crestor... went on the market no one expected that slow metabolizers would not be able to handle standard doses of it.
So some people died, or were damaged.
For those here who are interested in the Medwatch reports on drugs...this website gives them:
http://www.patientsville.com/
Here are the reports on Methadone:
http://patientsville.com/medication/...de_effects.htm
Keep in mind some reports are complex and involve multiple disease states, and/or complex drug cocktails. But many are very representative of the drug cited. Most drug reactions are not reported, and it is believed around 1% up to maybe 10% are. So keep that in mind also. Doctors balk at reporting, thinking admission of error may lead to liability suits.
This chart shows the ethnicity of drug metabolism differences:
http://www.dnadirect.com/web/article...s/186/ancestry
This chart gives the subcategories of the P-450 system and the drugs affected in each:
http://www.dnadirect.com/web/article...574439B11AEAF2
Quote:
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The CYP2D6 gene affects 25% of drugs in clinical use. If genetic test results indicate that a person is a 2D6 Poor Metabolizer, these drugs may not be effective due to improper or slow processing of the drug by the patient; or when several drugs are administered at once, their risk for severe adverse reactions may increase due to the slower metabolism of one of the drug’s in their regimen.
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We are approaching a time now in medicine where genetics of EACH patient makes a huge difference in therapeutic response, or risk from side effects or worse.
I foresee a computer eventually being used and testing of each person before prescribing drugs. Many doctors are confused by these charts and never test their patients to see if they are slow metabolizers. The tests remain expensive at this time and some insurances won't pay for them. So that hit or miss prescribing is still the norm.
Here is a link to methadone and drug interactions for it:
http://www.atforum.com/pdf/Drug_Interactions.pdf
It is complex however. But some posters here may want it, or want
to print it out, for reference.
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All truths are easy to understand once they are discovered; the point is to discover them.-- Galileo Galilei
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Weezie looking at petunias 8.25.2017
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