Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596240 (cancer pain)
 3,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.
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PMID:Morphine or oxycodone in cancer pain? 1120 1

Tramadol (Ultram, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) is considered a Step 2 analgesic under the World Health Organization's guidelines for the treatment of patients with cancer pain. It is a centrally acting analgesic that has affinity for opioid receptors and influences the action of norepinephrine and serotonin at the synapse. This dual mechanism of analgesia makes it unique among Step 2 agents. It is metabolized by CYP2D6, which increases the potentialfor drug interactions. Unlike other opioids, it does not cause respiratory depression. Tramadol has been studied in cancer pain and neuropathic pain. It compares well with low-dose morphine as an analgesic. The purpose of this review is to critically examine the pharmacodynamics, pharmacology, drug interactions, and adverse effects of the drug, and, based on the data presented, discuss the drug's role in cancer care.
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PMID:Tramadol: does it have a role in cancer pain management? 1731 16

Dihydrocodeine (DHC) is a semi-synthetic analogue of codeine which was formed by the hydrogenation of the double tie in the main chain of the codeine molecule. DHC is used as an analgesic, antitussive and antidiarrhoeal agent; it is also used for the treatment of opioid addiction. Limited data is available on the relative potency of DHC to other opioids. The analgesic effect of DHC is probably twice as potent as codeine for the parenteral and slightly stronger for an oral route. DHC possesses approximately 1/6(th) of the morphine analgesic effect when drugs are administered orally. In this article pharmacokinetics, pharmacodynamics, dosing guidelines, adverse effects and clinical studies of DHC in pain management are shown with focus on cancer pain. The impact of CYP2D6 activity on DHC analgesia was discussed and a proposal of calculation equianalgesic doses of DHC to other opioids was put forward.
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PMID:Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. 2054 Jun 93

In most cancer patients, pain is successfully treated with pharmacological measures using opioid analgesics for moderate to severe pain (strong opioids) alone or in combination with adjuvant analgesics (coanalgesics). Opioids for mild to moderate pain (weak opioids) are usually recommended in the treatment of cancer pain of mild to moderate intensity. There is a debate whether the second step of the WHO analgesic ladder comprising weak opioids such as tramadol, codeine and dihydrocodeine is still needed for the treatment of cancer and chronic pain since low doses of strong opioids show similar efficacy. However, many patients with mild, moderate and in some cases strong pain intensity are still successfully treated with weak opioids. All these drugs are metabolized through CYP2D6, an important enzyme for approximately 25% of all drugs administered in clinical practice. The aim of this review is to summarize data on the impact of CYP2D6 polymorphism on pharmacokinetics, pharmacodynamics and adverse effects of weak opioids.
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PMID:CYP2D6 in the metabolism of opioids for mild to moderate pain. 2149 59

This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.
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PMID:Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients. 2373 22

Chronic non-cancer pain is a debilitating condition associated with high individual and societal costs. While opioid treatment for pain has been available for centuries, it is associated with high variability in outcome, and a considerable proportion of patients is unable to attain relief from symptoms while suffering adverse events and developing medication dependence. We performed a review of the efficacy of pharmacogenomic markers and their abilities to predict adverse events, dependence, and associated economic costs, focusing on two genes: OPRM1 and CYP2D6. Data sources were articles indexed by PubMed on or before August 6, 2013. Articles were first selected after review of their titles and abstracts, and full papers were read to confirm eligibility. Initially, fifty-two articles were identified. Of these, 17 were relevant to biological actions of pharmacogenomic markers and their effect on therapeutic efficacy, 16 to adverse events, 15 to opioid dependence, and eight to economic costs. In conclusion, increasing costs of opioid therapy have made the advances in pharmacogenomics an attractive solution to personalize care with unclear repercussions related to the impact on costs, morbidity, and outcomes. This intersection of pharmacoeconomics and pharmacogenomics presents a unique platform to further examine current advances in clinical medicine and their utility in cost-effective treatment of chronic pain.
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PMID:Opioid therapy pharmacogenomics for noncancer pain: efficacy, adverse events, and costs. 2416 29

Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.
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PMID:[Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients]. 2594 6

History and clinical findings | We report about a 79 year old non-diabetic patient who was admitted to the emergency room with severe hypoglycemia (blood glucose level: 36 mg / dl and Glasgow Coma Scale Score: 3). After the infusion of G40 % her blood glucose level stabilised. The patient reported to have taken 50 mg of Tramadol during the night to treat her headache. Investigations and diagnosis | No other differential diagnosis for hypoglycemia (i.e. diabetes, insulinoma, severe liver or kidney disease) could be established. Therefore, we suspected a tramadol induced hypoglycemia. The mechanisms and the risk factors for this potential side effect remain unclear. The patient showed no abnormality in metabolism (CYP2D6) or membrane transport (OCT1) of tramadol. Treatment and course | No further treatment for hypoglycemic episodes was needed. The patient was discharged after the differential diagnosis and pharmacogenetic testing was completed. Conclusions | Hypoglycemia is a little known adverse effect after tramadol intake, which has only been published in few cases. Tramadol, a weak opioid analgesic classified as step 2 of the WHO cancer pain ladder, is used in moderate pain. Given the continuous rise in tramadol prescription due to better management of chronic pain, further investigation of this issue seems needed as well as an increased awareness amongst physicians.
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PMID:[Severe hypoglycemia following tramadol intake in a 79 year old non-diabetic patient]. 2770 96