Note: the EDNF.org website is in the process of moving, so links to it may not work. Once the new site is stable, I’ll update the links – 12/14/13
Thank you, SASO, for another page of excellent information and references!
EDS can result in altered medication metabolism
Dr. Tennent’s explanation about diffences in the CYP450 enzyme: http://www.ednf.org/index.php?option=com_content&task=view&id=2241
Opioid Metabolism – Howard S. Smith, MD – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/
CYP2D6 (http://en.wikipedia.org/wiki/CYP2D6) which if deficient can cause odd interactions, sensitivities or apparent allergies while other may not have any effect at all, which can include opiates. There can be normal, reduced, and non-existent CYP2D6 function:
- poor metaboliser—little or no CYP2D6 function, something anecdotally found in quite a few EDSers
- intermediate metabolizers;
- extensive metaboliser—normal CYP2D6 function;
- ultrarapid metaboliser—multiple copies of the CYP2D6 gene, with greater-than-normal CYP2D6 function (and could have even a fatal reaction from a first-time or even small dose of some medications or illicit drugs).
When to Suspect a Patient has CYP2D6 Deficiency (http://www.practicalpainmanagement.com/treatments/pharmacological/opioids/non-responsive-pain-patients-cyp-2d6-defect)
- Patient who reports a past or present history of non-responsiveness to codeine, hydrocodone, oxycodone, or tramadol.
- Patient who reports better pain relief with Darvocet-N-100 than hydrocodone (Vicodin®) or oxycodone (Percocet®).
- A patient who gives a history of significant toxicity or adverse reaction when they have taken specific Beta-Blockers, anti-depressants, or anti-psychotics.
A blood test for some cytochrome P450 genotypes has been available since 2005 so that we can now identify some people who will clear liver metabolized drugs from their body differently than the norm. People with two abnormal alleles will exhibit the least enzymatic activity and are referred to as poor drug metabolizers. Those individuals who have one normal (*1) allele and one abnormal (i.e., *10), are referred to as heterozygote’s and will exhibit intermediate drug metabolism. It is also possible for about 2% of whites and >25% of Saudi Arabians to have duplication of the functional *1 gene and results in ultra drug metabolism. Up to 13 copies of CYP-2D6 in the same person have been reported.
http://www.ncbi.nlm.nih.gov/pubmed/14996240 Genetic polymorphism [of P-450] can lead to important potential clinical consequences for some opioids, anticonvulsants (phenytoin), benzodiazepines (diazepam), muscle relaxants (succinylcholine), antidepressants (imipramine, nortriptyline, venlafaxine), typical neuroleptics, alcohol, antihypertensives (propranolol, timolol), local anesthetics (procainamide), L-dopa, nicotine, and warfarin.
http://www.medpagetoday.com/MeetingCoverage/APA/9355 Testing depressed inpatients for abnormalities in cytochrome P450 drug-metabolizing enzymes may be warranted, a researcher said here.
About 20% of patients hospitalized for depression had at least three defects in CYP450 genes, reported Gualberto Ruaño, M.D., Ph.D., of Genomas Inc. in Hartford, Conn., at the American Psychiatric Association annual meeting here.
He said these patients tended to do poorly on initial treatment with standard drugs. Defects in drug-metabolizing enzymes may be an important reason, he said.
Genetic Testing for Drug Metabolism
Human body routinely takes in nutrients ( Carbohydrates, fats protein, vitamins, minerals and water for optimum cellular functions. However, additional complex biochemicals such as caffeine, drugs( Plavix) and toxins enter the body. These complex chemicals are broken down to make pharmacologically active and/or inactivate before they are excreted through the kidneys. Break down of these chemicals are carried out in the liver by metabolizing enzymes including cytochrome P450 (Cyp450) which forms the major group. Out of the 57 Cyp450 enzymes, 15 are associated with drug metabolism. Based on the genetic variations of these enzymes and their combination, drug metabolism is grouped into four categories; extensive ( normal) metabolizer, intermediate metabolizer, poor metabolizer, and ultra-rapid metabolizer. Therefore, testing for these genetic variations can help in the proper dosage preventing potential adverse side effects.
More than 25% of the drugs are metabolized by CYP2D6 which including cancer drugs( e.g tamoxifen) antidepressants(e.g.Fluoxetine) and anti narcotic analgesics ( e.g Codeine). Enzyme CYP2C19 metabolizes hormones, and precescription drugs (e.g Omerprazole,Clomipramine and Clopidogrel-Plavix) warfarin by CYP2C9.
Partial list of different enzymes required for example medications list…see which match up with the medications you take to know what enzymes are required…or which ones you tried that didn’t work and which enzymes were required for those: http://medicine.iupui.edu/clinpharm/ddis/ClinicalTable.aspx
A more complete list: http://www.cnsspectrums.com/userdocs/ArticleImages/08CNS_Q&Atable1(big).jpg