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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.
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PMID:Oxycodone: a pharmacological and clinical review. 1752 40

Nausea and vomiting are distressing symptoms in advanced cancer patients. The causes of nausea and vomiting are multifactorial. Among the causes is opioid therapy, the mainstay of cancer pain management. When nausea or other opioid side effects occur, it may hamper pain management and undermine the quality of life of cancer patients. Risperidone exerts an antiemetic effect in animals, but there has been no clinical report on its antiemetic activity. We conducted a retrospective chart review to examine whether risperidone is useful for opioid-induced nausea and vomiting in advanced cancer patients (n=20). Risperidone was given as doses of 1mg once a day. Complete response was observed in 50% of patients (10/20) for nausea and 64% (7/11) for vomiting. Sedation (n=2) was documented as an adverse effect. This observation suggests that risperidone can be an effective antiemetic drug in the treatment of refractory opioid-induced nausea and vomiting in advanced cancer patients.
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PMID:A retrospective chart review of the antiemetic effectiveness of risperidone in refractory opioid-induced nausea and vomiting in advanced cancer patients. 1754 49

Cancer pain is a prevalent and serious public health issue, and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker, in cancer pain. A Phase IIa, open-label, multicenter, dose-escalation study of intramuscular tetrodotoxin was conducted in patients with severe, unrelieved cancer pain. The study design called for six ascending dose levels of intramuscular tetrodotoxin, administered over a four-day treatment period in hospitalized patients, with six patients to be enrolled within each successive dose level. Twenty-four patients underwent 31 courses of treatment at doses ranging from 15 to 90 microg daily, administered in divided doses, over four days. Most patients described transient perioral tingling or other mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but two patients experienced a serious adverse event, truncal and gait ataxia, that resolved over days. Seventeen of 31 treatments resulted in clinically meaningful reductions in pain intensity, and relief of pain persisted for up to two weeks or longer. Two patients had opioids held due to narcosis concurrent with relief of pain. Somatic, visceral, or neuropathic pain could all respond, but it was not possible to predict which patients were more likely to have an analgesic effect. Tetrodotoxin was overall safe. It effectively relieved severe, treatment-resistant cancer pain in the majority of patients and often for prolonged periods after treatment. It may have a novel mechanism of analgesic effect. Further study is warranted.
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PMID:An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. 1766 11

Fentanyl buccal tablet (FBT) is a new opioid formulation providing rapid-onset analgesia for the treatment of breakthrough pain (BTP). This study evaluated FBT for BTP in opioid-tolerant patients with chronic cancer pain. The study had a randomized, double-blind, placebo-controlled design and was conducted at 30 outpatient treatment centers in the United States. Following open-label titration, patients were randomly assigned to 1 of 18 double-blind dose sequences (7 FBT tablets, 3 placebo) to treat 10 BTP episodes. Pain intensity was measured on an 11-point scale (0 = no pain; 10 = worst pain). The primary efficacy measure was the sum of pain intensity differences (PIDs) for the first 60 minutes (SPID60); secondary efficacy measures included PIDs and pain relief (PR) measured from 5 minutes through 2 hours. Adverse events (AEs) were recorded. Of 129 patients enrolled, 87 entered the double-blind phase. SPID60 significantly favored FBT versus placebo (mean +/- SE, 9.7 +/- 0.63 vs 4.9 +/- 0.50; P < 0.0001). Secondary measures also favored FBT: PIDs and PR showed significant differences versus placebo at 10 minutes (0.9 vs 0.5; 0.815 vs 0.606, respectively, P < 0.0001) and all subsequent time points (P < 0.0001). AEs were typical of opioids (eg, nausea, dizziness, fatigue). In conclusion, in this study of opioid-tolerant patients with chronic cancer pain and BTP, FBT was efficacious, well tolerated, demonstrated rapid onset of analgesia (within 10 minutes), and had a sustained effect.
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PMID:Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant patients with cancer-related chronic pain. 1770 23

Our objective was to investigate the efficacy and safety of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, in subjects with non-cancer pain and opioid-induced bowel dysfunction (OBD), and to identify at least one treatment regimen that improves OBD. Following a 2-week baseline period, 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week (with >or=25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to >or=30 mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia.
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PMID:Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. 1816 18

We established the Terminal Care Study Group, consisting of physicians, pharmacists, and nurses, in September 2001, and developed the group into the Palliative Care Team. We have surveyed the state of concomitant medications immediately before and at the beginning of opioid usage (except injections) to assess the role of the Palliative Care Team. The survey period was 3 years from October 1, 2002 to September 30, 2005. While the frequency of the prescription of non-steroidal anti-inflammatory drugs (NSAIDs), laxatives, or antiemetics before the beginning of opioid administration did not differ significantly among the 3 periods, that at the beginning of opioid administration increased significantly in 2003 compared with 2002, and increased further in 2004. Many of the drugs used were those that were recommended in our cancer pain management program. Thus, the activities of the Palliative Care Team are considered to have led to proper measures for the control of the major adverse effects of opioids such as constipation and nausea/vomiting in addition to pain control in accordance with the WHO's pain ladder, and also contributed to improvements of the patients' QOL.
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PMID:Assessment of palliative care team activities--survey of medications prescribed immediately before and at the beginning of opioid usage. 1823 78

Cancer pain is a serious public health issue and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker. This randomized, placebo-controlled, parallel design study of subcutaneous tetrodotoxin, in patients with moderate or severe unrelieved cancer pain persisting despite best available treatment, involved 22 centers across Canada. The design called for tetrodotoxin administered subcutaneously over Days 1-4 with a period of observation to Day 15 or longer. All patients could enroll into an open-label extension efficacy and safety trial. The primary endpoint was the proportion of analgesic responders in each treatment arm. Eighty-two patients were randomized, and results on 77 were available for analysis. There was a nonstatistically significant trend toward more responders in the active treatment arm based on the primary endpoint (pain intensity difference). However, analysis of secondary endpoints, and an exploratory post hoc analysis, suggested there may be a robust analgesic effect if a composite endpoint is used, including either fall in pain level, or fall in opioid dose, plus improvement in quality of life. Most patients described transient perioral tingling or other mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but one patient experienced a serious, adverse event, truncal and gait ataxia. This trial suggests tetrodotoxin may potentially relieve moderate to severe, treatment-resistant cancer pain in a large proportion of patients, and often for prolonged periods following treatment, but further study is warranted using a composite primary endpoint.
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PMID:Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study. 1824 39

Ketamine used in conjunction with other analgesics has dissociative, analgesic, sedative, and amnesic properties. Ketamine potentiates opiates and analgesics, is rapid acting, and is relatively safe. The United Kingdom and United States use ketamine with opioids in adjuvant pain management for a variety of conditions, including cancer pain. Adults and children benefit from the analgesic effects of these medications, especially at the end of life when the reduction of severe cancer pain has refractory or dose-limiting effects. For adults, ketamine and opioids are administered by a patient-controlled analgesia pump. The medication combination has decreased use of opioids and increased activities of daily living. Nursing considerations include close monitoring of vital signs during the initial dosage and follow-up observations of the effectiveness of the medications. Vital signs are checked every four hours after the initial dosage along with evaluation of the effectiveness of the dosage and observation for signs of oxygenation of tissue. Patients have better mobility and quality of life when receiving ketamine as an adjuvant therapy, which promotes assistance with their nursing care. Side effects may occur from administering ketamine and include nausea, vomiting, dizziness, and emotional distress. Standard orders help alleviate problems with those symptoms.
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PMID:The use of ketamine as adjuvant therapy to control severe pain. 1856 30

Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.
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PMID:Fentanyl buccal tablet. 1830 3

The oral administration of strong opioids like morphine is a very effective treatment in cancer pain. However, these analgesics are rarely prescribed for patients suffering from severe "non-malignant" pain. We examined the effects of oral opioids (morphine sulphate tablets, buprenorphine and levomethadone) given to patients with intractable rheumatic pain, which were refractory to other therapeutic measures. The origin of pain was inflammation or a degenerative lesion of the spine. Within a period of more than 3 years, 12 patients were treated accordingly. In 9 patients we could achieve sufficient pain relief, two of them showing improvement only after having changed the initially prescribed drug. We had to stop opioid medication in two patients because of side-effects and, moreover, in one patient because of failure to produce analgesia. 775 weeks of treatment were documented until December 31th, 1990, with an individual duration ranging from 11 to 145 weeks. It was necessary to increase the dose of morphine in the course of treatment of one patient, who is up to now being treated for more than 77 weeks. In all other patients the doses were either stable or varied. No severe side-effects such as respiratory depression were associated with long-term opioid therapy. Constipation was observed in 4 patients, nausea in two patients and urinary retention in one patient. These side-effects could be well treated by an additional medication. No drug abuse, dependence or tolerance were observed. Strong opioids are not analgesics of first choice in patients with rheumatic disease, but an opioid medication should be considered-as well as in patients with intractable pain caused by another disease-when alternative therapeutic measures have failed. The principles of opioid medication in rheumatic pain are similar to those in patients with cancer pain.
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PMID:[Opioids in "non-malignant" pain-results of long-term treatment in patients with rheumatic disease.]. 1841 94


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