{"id":771,"date":"2012-06-01T00:00:47","date_gmt":"2012-06-01T07:00:47","guid":{"rendered":"http:\/\/rhochistj.org\/RCP_TEST\/?p=771"},"modified":"2014-02-17T16:26:52","modified_gmt":"2014-02-17T23:26:52","slug":"impact-gender-race-efficacy-opiods","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/impact-gender-race-efficacy-opiods\/","title":{"rendered":"Impact of Gender and Race on the Efficacy on Opiods"},"content":{"rendered":"

By: Lunbao (Jerry) Huang, Pharm.D.\u00a0 Candidate c\/o 2013<\/span><\/p>\n

–<\/p>\n

Pain is a very difficult condition to manage, as clinicians have only subjective findings to work with.\u00a0 Opioid medications are currently the cornerstones for the management of moderate to severe pain; however, it is often problematic to determine a patient\u2019s real \u2018need\u2019 for opioids.\u00a0 Physicians\u2019 clinical judgments help to create individualized medication regimens for patients with pain.\u00a0 The need for specialized opioid dosing is most likely multifactorial, including both genetic and environmental predispositions to pain.\u00a0 Health care providers must account for these factors by investigating pharmacogenomic relationships through pharmacokinetic and pharmacodynamic studies.\u00a0 The field of pharmacogenomics is particularly under increasing investigation for the enhancement of drug therapy outcomes.\u00a0 Differences in age, gender, and ethnicity have various effects on a drug\u2019s receptor binding, potency, absorption, distribution, metabolism, and excretion.<\/p>\n

Both age and gender are important determinants of central nervous system (CNS) structure and function.\u00a0 Binding with the mu-<\/i>opioid receptor within the CNS is of particular interest.\u00a0 One study examined age- and gender-associated variations with positron emission tomography (PET) and the radiotracer carfentanil.1<\/sup>\u00a0 There were two analyses: first a retrospective analysis of a group of 24 men and 12 women, and second, a prospective study of a group of 12 men and 18 women.\u00a0 This study found that the mu-<\/i>opioid receptor binding potential (Bmax<\/sub>\/Kd<\/sub>) increased with age in neocortical areas of the brain.\u00a0 Furthermore, there was higher mu-<\/i>opioid binding in women.\u00a0 In-vivo mu-<\/i>opioid binding declined in postmenopausal women to levels below those of men.1<\/sup>\u00a0 This indicates that women\u2019s reproductive status (reproductive age versus postmenopausal) may influence the function of CNS opioid receptor systems.\u00a0 Therefore, data suggests that both age and gender are important variables to consider in the investigation of opioid systems in humans.<\/p>\n

A study of pentazocine, an opioid that acts at kappa<\/i>\u2212receptors, revealed better postoperative analgesia in females than in males.2<\/sup>\u00a0 There was a follow-up study for patients undergoing surgery for the removal of their wisdom teeth.\u00a0 The study compared the analgesic efficacy of two other predominantly kappa<\/i>\u2212opioid analgesics, nalbuphine, and butorphanol.\u00a0 Results confirmed that nalbuphine and butorphanol produced significantly greater analgesia in females as compared with males.\u00a0 Authors concluded that kappa<\/i>\u2212opioid analgesia is greater in females than in males, most likely due to differences in kappa<\/i>\u2212opioid\u2212activated endogenous pain modulating circuits.3<\/sup><\/p>\n

Metabolism of opioid medications also affects the efficacy of opiods.\u00a0 Race is one of the determinants of CYP450 2D6 variability.\u00a0 The prevalence of CYP2D6 poor metabolizers is approximately 6\u201310% in Caucasian populations, and as low as 2% in Asian populations.4<\/sup>\u00a0 The frequency of poor metabolizers among blacks is greater than that for whites.\u00a0 In addition, 2D6 enzyme appears to be greatest among Middle Eastern and North African populations.5<\/sup> As we know, morphine is metabolized hepatically via conjugation with glucuronic acid.\u00a0 The main metabolites are morphine-6-glucoronide (active analgesic) and morphine-3-glucuronide (inactive).\u00a0 Minor metabolites include morphine-3-6-diglucuronide, normorphine (active), and morphine 3-ethereal sulfate.\u00a0 The body metabolizes oxycodone via CYP3A4 to noroxycodone (weak analgesic), noroxymorphone, and alpha- and beta-noroxycodol.\u00a0 CYP2D6 also mediates oxycodone metabolism to produce oxymorphone (analgesic), alpha-, and beta-oxymorphol.\u00a0 Codeine is also bioactivated to morphine, a strong opioid agonist, by CYP2D6.\u00a0 The efficacy and safety of codeine, morphine, and oxycodone are subject to CYP2D6 polymorphisms.\u00a0 Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas there is a higher risk of morphine toxicity in ultra-rapid metabolizers.\u00a0 We fortunately have information interpreting CYP2D6 genotype test results to guide the dosing of codeine.6<\/sup><\/p>\n

In 2011, there was an announcement calling for translational and genetic research for identifying new targets for new analgesics to be developed based on pharmacogenomics.7<\/sup>\u00a0 Voltage-gated sodium, calcium, and potassium channels were addressed, for which SCN9A, CACNA1B, KCNQ2, KCNQ3, and yet undiscovered receptors could become new targets for pain control.\u00a0 Research on the genetic modulation of pain has already identified variants in these genes; pharmacogenetic assessments of new analgesics could be relevant.\u00a0 The increased number of pharmacogenetic modulators of analgesic actions presents opportunities for broader clinical implementation of genotyping information.<\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Zubieta JK, Dannals RF, Frost JJ et al.\u00a0 Gender and Age Influences on Human Brain Mu-<\/i>Opioid Receptor Binding Measured by PET. Am J Psychiatry<\/i> 1999;156:842\u20148.<\/li>\n
  2. Gear, R.W.\u00a0 et al.\u00a0 Gender difference in analgesic response to the kappa-opioid pentazocine.\u00a0 Neurosci Lett<\/i> 1996;205:207\u22129.<\/li>\n
  3. Gear RW, Gordon NC, Heller P et al.\u00a0 Kappa<\/i>\u2212opioids produce significantly greater analgesia in women than in men.\u00a0 Nature Med<\/i> 1996;2:1248\u201450.<\/li>\n
  4. Rossi S (Ed.) Australian Medicines Handbook.\u00a0 Adelaide: Australian Medicines Handbook.\u00a0 (2004).<\/li>\n
  5. Gaedigk A, Bradford LD, Marcucci KA, Leeder JS.\u00a0 Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans.\u00a0 Clin Pharmacol Ther<\/i> 2002;72(1):76\u201489.<\/li>\n
  6. Crews KR, Gaedigk A, Dunnenberger HM, et al.\u00a0 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.\u00a0 Clin Pharmacol Ther<\/i> 2012;91(2):321\u20146.<\/li>\n
  7. L\u00f6tsch J, Geisslinger G.\u00a0 Pharmacogenetics of new analgesics.\u00a0 Br J Pharmacol<\/i> 2011;163(3):447\u201460.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Lunbao (Jerry) Huang, Pharm.D.\u00a0 Candidate c\/o 2013 – Pain is a very difficult condition to manage, as clinicians have only subjective findings to work with.\u00a0 Opioid medications are currently the cornerstones for the management of moderate to severe pain; however, it is often problematic to determine a patient\u2019s real \u2018need\u2019 for opioids.\u00a0 Physicians\u2019 clinical…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4],"tags":[190,668,343,543,58,61,65,120,1160,13,2227,314,2251,20,376,14,538,363,968,1543,47,167,256,671,31,36,240,21,539,453,1145,1161,1061,1370],"class_list":["post-771","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured","tag-account","tag-acid","tag-and","tag-beta","tag-brain","tag-calcium","tag-codeine","tag-condition","tag-control","tag-drug","tag-ebola-virus-disease","tag-for","tag-guidelines","tag-health","tag-human","tag-medication","tag-morphine","tag-of","tag-one","tag-oxycodone","tag-pain","tag-poor","tag-potassium","tag-r","tag-research","tag-risk","tag-sodium","tag-study","tag-sulfate","tag-system","tag-test","tag-therapy","tag-with","tag-women"],"views":754,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/771","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=771"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/771\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=771"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=771"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=771"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}