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Query: UMLS:C0027497 (nausea)
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The role of the coxibs in the management of osteoarthritis and rheumatoid arthritis has been widely discussed, but there are other potential applications for the coxibs that have received less attention. Here we consider the use of the coxibs in acute pain syndromes such as primary dysmenorrhea and the pain associated with dental extraction, as well as considering their application in chronic low back pain and cancer pain. Another area where the coxibs may prove particularly beneficial is in the management of post-surgical pain. Traditional post-surgical analgesia has involved the use of non-selective NSAIDs and opioids, but these agents can be associated with side effects such as post-operative bleeding, gastrointestinal problems, nausea, and constipation. Because the coxibs do not inhibit COX-1 dependent platelet aggregation like traditional NSAIDs, the risk of post-surgical bleeding is reduced. The careful application of coxibs as part of a multi-modal approach to pain management in the perioperative period can reduce the requirement for opioid medications and thus reduce the risk of post-operative complications such as ileus. In the future, coxibs are likely to play an important role in multi-modal perioperative analgesic regimens with the aim of reducing post-operative periods of convalescence.
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PMID:Strategies in pain management: new and potential indications for COX-2 specific inhibitors. 1260 54

Morphine, the recommended drug for the management of moderate to severe cancer pain, is metabolized predominantly to the glucuronides morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). The quantitative clinical importance of these metabolites following the administration of oral morphine is unclear. This study investigates the relationship between plasma concentrations of morphine (M), M6G, M3G and clinical effects in patients receiving sustained release oral morphine for cancer-related pain. Peak and trough plasma concentrations of morphine and its metabolites were determined by high-performance liquid chromatography (HPLC). At corresponding time points, pain [Visual Analogue Scales (VAS), Verbal Rating Scales (VRS), Pain Relief Scores (PRS)] and toxicity (VAS and VRS) were assessed. Renal and liver function tests were performed. Forty-six patients were included in the study. There was a significant correlation between dose and both peak and trough plasma M, M6G and M3G (r > 0.60, P < 0.001 for each). Differences between peak and trough M, M6G, M3G, M+M6G, M6G:M, M3G:M and M3G:M6G were all significant (P < 0.001 for each). Pain was generally well controlled in the group, with a median VAS of 15 mm at the peak blood sampling time point. The differences between peak and trough values for VAS pain, VAS nausea and VAS drowsiness were not statistically significant (P = 0.078, 0.45 and 0.099, respectively). There were no differences in peak or trough morphine and metabolite concentrations or ratios between patients with low (< median) or high pain scores. Similarly, there was no significant relationship between high and low plasma concentrations and clinical effect. This study did not identify a simple relationship between plasma concentrations of morphine, morphine metabolites or metabolite ratios and clinical effects in patients with cancer and pain who were receiving chronic oral morphine therapy. Although overall pain control was good, there was marked interpatient variability in the dose of morphine and the plasma concentrations necessary to achieve this degree of analgesia.
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PMID:Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain. 1270 50

According to the three step-ladder analgesics in patients with cancer pain, adjuvant drugs are required for pain relief according to the pain character and also to reduce side effects of opioids. Pain clinicians sometimes want to decide to jump directly from naive and mild opioid to transdermal therapeutic system (TTS) fentanyl with less side effects. We investigated the safety, efficacy, and satisfaction of the patients of TTS fentanyl converting from opioid-naive and mild-opioid with adjuvant drug medications in related to dose cascade of TTS fentanyl. Both opioid-naive (n=3) and opioid-using (n=34) patients started with TTS fentanyl in the lowest available delivery rate (25 microg/hr) with rescue medication. A numeric rating scale (NRS, from 0=no pain to 10=worst pain imaginable), satisfaction of the patients with the transdermal therapy and side effects were recorded everyday during 29 days. Average reductions of NRS scores were 1.79 and 2.77, and the mean doses were 35.14 and 44.12 microg/hr on the 15th and 29th day, respectively. Reported level of satisfaction with the transdermal patch and generalized pain management were 'completely satisfied' and 'satisfied'. Frequent side effects were nausea, vomiting, and constipation. In conclusion, initial application of TTS fentanyl with proper adjuvant medications is effective, safe, and well tolerated.
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PMID:Initial dose cascade of TTS fentanyl with proper adjuvant medications in cancer pain. 1455 29

Opioid-induced sedation is a major complication in patients with cancer pain. This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain. Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled. Donepezil 5 mg was given every morning for 7 days. Changes between baseline and Day 7 in sedation, pain, fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness of donepezil was measured by the patient at the end of the study. In 20 evaluable patients, sedation, fatigue, anxiety, well-being, depression, anorexia and problems with sleep were significantly improved. Side effects included nausea, vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however, the treatment was well tolerated. Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain. Randomized controlled trials of this agent are justified.
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PMID:The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study. 1458 55

Neurolytic celiac plexus block is an established, well-developed procedure and the most accepted and applied in visceral pain; recognized by the WHO and the IASP, it is very good in palliative management of cancer pain in visceral of superior hemiabdomen. However, conventional techniques in celiac plexus have not been successful in patients with organomegaly and/or anatomic abnormalities, except when splanchnic nerve neurolytic blockade is used. On the other hand, conventional techniques in splanchnic nerves are highly associated with complications such as paraplegia, pneumothorax and liver or renal punction. For these reasons an alternative option has ben designed, termed transdiscal percutaneous approach of splanchnic nerves under tomographic control; this technique affords the option of improving accuracy and performance with minimum risks, particularly lung puncture and its consequences. Under this technique, 64 superior hemi-abdomen cancer patients initiated such a study (four without morphine treatment quit the study), 55% females and 45% males, visceral pain syndrome 65%, and mixed, 35%. Side effects were dyspnea 5%, hypotension 26.7%, nausea 31.7%, diarrhea 83.3% in which diarrhea means increased peristalsis showing adequate sympathetic inhibition via splanchnic nerves), vomiting 28.3%, punction-site pain 46.7%, aorta punction 6.7%, anal pleural punction 5%. All these incidents were dealt with by conservative treatment. Student t test showed that pain intensity in all measurements after procedure was different in comparison to basal pain intensity prior to procedure (p<0.05), emphasizing that at the 12th, 18th and 24th months, there was noticeable reduction in participants number with eight, five and four participants, respectively. Morphine intake at week 1, and 1, 2, 3, 6 and 12 months after procedure was different from basal intake prior to procedure (p<0.05) with same noticeable reduction in participant numbers at last stages. Butylhioscine intake at week 1, 1, 2, 3 and 6 months after procedure was different from basal intake prior to procedure (p<0.05). NSAIDs consumption was likely during 2 months after procedure (p<0.05). Linear regression showed that butylhioscine and morphine explained low percentage of pain intensity variance, controlling statistically that effect over pain. There were no differences in pain pathophysiology with regard to cancer type. Transdiscal percutaneous approach of splanchnic nerves guided by CAT is an alternative with minimal risks, as with lung punction, confirming that inhibiting splanchnic nerves has advantages in pain release, reducing and/or eliminating morphine consumption.
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PMID:[Transdiscal percutaneous approach of splanchnic nerves]. 1461 7

The clinical importance of routine drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. We measured morphine, M6G and M3G serum concentrations in cancer pain patients receiving oral (n = 263, median dose 80 mg/24 hours) or subcutaneous (sc) (n = 35, median dose 110 mg/24 hours) morphine. Regression analyses were performed to investigate if serum concentrations of morphine, M3G and M6G predicted pain intensity (Brief Pain Inventory), health-related quality-of-life variables (EORTC QLQ-C30) and cognitive function (Mini-Mental Score). Serum concentrations were also compared in patients categorized as morphine 'treatment successes' and 'treatment failures'. We observed that serum concentrations of morphine, M6G or M3G did not predict pain intensity, cognitive function, nausea or tiredness. 'Treatment failures' caused by nausea, tiredness, cognitive failure or constipation did not have statistically significant different morphine, M6G and M3G serum concentrations than patients classified as 'treatment successes'. In conclusion, this study did not observe any concentration-effect relationships of morphine, M3G or M6G with pain intensity, nausea, constipation, tiredness or cognitive failure in blood samples obtained during routine clinical drug monitoring in cancer patients. This result suggests that therapeutic drug monitoring as a routine tool during chronic morphine treatment has limited value for clinical decision making.
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PMID:Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients. 1469 19

Use of complementary and alternative therapies is widespread among cancer patients. Throughout the world cancer patients try many questionable or unproven treatment methods. The reasons for adopting these therapies are complex and are related to the social and cultural contexts of their geographical locations. In case of severe illness, the desire to leave no stone unturned is a powerful motivator. In developing countries, ignorance, socioeconomics, and inadequate access to mainstream medical facilities are major factors that play an important role for patients opting for alternative therapies that are replacements for mainstream treatment. Whereas in developed countries a significant proportion of cancer patients try complementary therapies as adjuncts to mainstream care for management of symptoms and to improve quality of life. Many alternative therapies, including pharmacological and biological treatments, remain highly controversial but at the same time are very popular. Evidence from randomized trial supports the value of hypnosis for cancer pain and nausea; relaxation therapy and massage for anxiety; and acupuncture for nausea. This article reviews the different popular alternative cancer therapies practiced in India and neighboring south east Asian countries to project the current international scenario on complementary and alternative cancer therapies.
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PMID:Complementary and alternative cancer therapies: past, present and the future scenario. 1507 98

The transdermal therapeutic system with fentanyl was released in Germany in 1995. Before and after the release several clinical trials were performed in our pain management unit and in other German pain centers, showing good efficacy after initial dose titration with intravenous patient-controlled analgesia or switching from pretreatment with oral morphine or other opioids. A sequential trial showed less use of laxatives with transdermal fentanyl compared to pretreatment with oral morphine. Safety and efficacy of the transdermal system in clinical practice were confirmed in a nationwide survey with 1005 patients, nearly all of them with cancer pain. Most patients had been treated with opioids, though 22% had received no opioids or only as required before initiation of transdermal fentanyl. The mean duration of transdermal treatment was 71 +/- 83 days. Pain relief with transdermal therapy was swift and efficient. Adverse events with the possibility of a causal relationship to transdermal therapy were documented for 26% of the patients, most frequently nausea, vomiting, constipation and drowsiness. Severe neurotoxic or respiratory complications were reported only rarely. Problems with transdermal application were reported by 12% of the patients, with patch detachment and dermatologic symptoms on the site of application being most frequent. Most patients showered regularly with the patches and only three patients reported that patches became loose under the shower or in the bathtub. In a recent prospective trial driving ability was tested in patients with continuous non-cancer pain, who had received stable doses of transdermal fentanyl. Data were available from 90 healthy volunteers matched to 30 patients, of whom 9 were excluded from the analysis because they took additional drugs in violation of the protocol. None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls. In conclusion, experience with the transdermal therapeutic system with fentanyl has been gathered in clinical trials, a large nationwide survey and clinical practice since the release in 1995. The conversion table based on a conversion ratio of 100 : 1 was safe and efficient in trials and clinical practice. Transdermal fentanyl has become a wellknown and frequently used opioid in the treatment of chronic cancer and non-cancer pain in Germany.
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PMID:Clinical experience with transdermal fentanyl for the treatment of cancer pain in Germany. 1509 25

Patients with moderate-to-severe malignancy-related pain require opioid pharmacotherapy. Many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undue suffering and diminished quality of life. Pain associated with malignancy and its treatment may exacerbate other symptoms associated with cancer, including nausea, fatigue, weakness, dyspnoea, constipation and impaired cognition. The choice of analgesic pharmacotherapy should be individualised and based on the intensity of pain reported by the patient, rather than its specific aetiology. When selecting pain management pharmacotherapy, the healthcare provider should consider the patient's pain level, activity level and any comorbid illness. Intolerable adverse effects, ineffective pain relief or a change in the patient's clinical status can dictate the need for a new pain management regimen. Healthcare providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal formulations of fentanyl and buprenorphine are effective pharmacotherapy that can be safely used for cancer patients with pain. However, clinicians need to be cognisant that the US/UK manufacturer's recommendations for equianalgesic dose administration of transdermal fentanyl may result in initial doses that produce subtherapeutic concentrations and unrelieved pain in some patients. A less conservative dose administration algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine : microg/h of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualise cancer pain pharmacotherapy.
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PMID:Practice guidelines for transdermal opioids in malignant pain. 1553 67

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.
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PMID:Opioids in chronic non-cancer pain: systematic review of efficacy and safety. 1602 19


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