Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Much is known about opioid metabolism, which is critical in administering these agents to the elderly. Fear of addiction and tolerance are the major barriers to their use among patients as well as health-care professionals. Addressing these issues early in the initiation opioid therapy will help to alleviate these concerns. Once therapy with an opioid is initiated, the role of renal function is critical. Because many metabolites of the opioids are renally cleared and have activity either in analgesia or as undesired side effects, it is critical to be aware of the creatinine clearance (not just serum creatinine) in the elderly. The initiating doses of the opioids can be equal to that of younger patients, but the clinician should anticipate using a longer frequency of dosing interval or smaller doses during the course of therapy. Methadone, propoxyphene, and meperidine are not recommended for use in elderly people, because of the toxicity of their metabolites. Of all the unwanted effects of the opioids, the most difficult to deal with is that of constipation. Here, an aggressive approach using bowel stimulating laxatives is critical in order to prevent this problem. It is anticipated that a variety of newly formulated opioids will shortly be available for clinical use. Finally, as a better understanding of the neurophysiology of pain is gained, the clinician can anticipate having more analgesic opioids that target their receptors without agonist or antagonist effect on other opioid receptors. This will allow the clinician to better relieve pain with a minimum of unwanted side effects.
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PMID:Opioid analgesic drugs in the elderly. 885 41

Fentanyl is a synthetic opioid with short-acting analgesic activity after intravenous or subcutaneous administration. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery via the transdermal therapeutic system (TTS). These systems are designed to release the drug into the skin at a constant rate ranging from 25 to 100 micrograms/h, multiple systems can be applied to achieve higher delivery rates. Initially, much of the clinical experience with fentanyl TTS was obtained in patients with acute postoperative pain. However, because of the increased risk of respiratory complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide including the US, its use is not restricted to chronic cancer pain; the drug is also available for treatment of general chronic pain, including that of nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation of the drug within skin tissue results in a significant delay (17 to 48 hours) before maximum plasma concentration is achieved. Approximately half of the cancer patients converted to transdermal fentanyl from other opioid agents required increased dosages after initial application of the patch. However, concomitant use of short-acting morphine maintained pain relief during the titration period, and the use of such supplementary medication decreased with the duration of fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50% decrease (less pain) during transdermal fentanyl therapy compared with previous opioid treatment. In addition, patient preference for fentanyl TTS was indicated by the number of patient requests (up to 95%) for continued use of the drug at the end of the study. Although fentanyl TTS is contraindicated in patients postoperatively, the efficacy of fentanyl via the transdermal route was investigated in this patient group. Supplementary patient controlled analgesia was significantly reduced in patients who received fentanyl TTS 75 micrograms/h compared with placebo, although this was not apparent until > or = 12 hours after application. Data evaluating pain relief, which was assessed by VAS pain scores, were inconclusive. Preliminary data, although from relatively small numbers of patients, indicate that transdermal fentanyl may be useful in the management of chronic non-malignant pain. Indeed, some patients whose pain was previously uncontrolled became completely pain free. The most frequently occurring adverse events during fentanyl TTS therapy (as with other opioid agents) included vomiting, nausea and constipation, although vomiting and nausea were not clearly associated with the drug. The most serious adverse event was hypoventilation, which occurred more frequently in postoperative (4%) than in cancer patients (2%). In surgical patients, fentanyl-associated respiratory events (reduced respiratory rate and apnoea) generally occurred within 24 hours of patch application; however, there were isolated reports of late onset (> or = 36 hours postsurgery) fentanyl-associated respiratory depression. In cancer patients, the incidence of constipation was reduced by up to two-thirds after switching from oral morphine to transdermal fentanyl. Transient skin irritation associated with the plastic patch or the adhesive, rather than the drug, was reported in a maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative to other opioid agents, which are also recommended on the third step of the WHO analgesic ladder, in the management of chronic malignant pain. Preliminary data indicate that it may be useful in the management of chronic nonmalignant pain. The advantages offered by fentanyl TTS over traditional methods of chronic pain control include its ease of administration, less constipation and the 3-
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PMID:Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. 901 Jun 52

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastrointestinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique after lactulose ingestion. Morphine significantly increased oral-cecal transit time from 114.6 +/- 37.0 minutes (mean +/- SD) to 158.6 +/- 50.2 minutes (p < 0.001). Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time (110.4 +/- 45.0 minutes; not significant compared with baseline; p < 0.005 compared with morphine alone). These sessions were then followed by single-blind evaluations of descending doses of methylnaltrexone. We observed that 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time (p < 0.005 compared with morphine alone), and a dose-dependent response was obtained. There was no correlation between oral methylnaltrexone effects on the transit time and the drug plasma concentration, suggesting direct preferential luminal effects of oral methylnaltrexone. Oral methylnaltrexone may have a clinical value in the prevention and treatment of constipation induced by long-term opioid use.
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PMID:The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time. 912 64

Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.
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PMID:Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. 976 15

Opioid analgesics represent one of the most important tools in a sequential pharmacological approach to oncological pain relief. They are recommended by the WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate analgesia. However, the use of opioids is limited because of their numerous and often severe adverse effects. This aspect of opioids has motivated continuous research projects aimed at discovering drugs that can provide maximum pain relief but with improved tolerability. Tramadol is a new, centrally acting analgesic with a dual mechanism of action. It shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release. From a pharmacokinetic standpoint, tramadol offers high bioavailability, with similar patterns after oral or parenteral administration (half-life 5 to 7 hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma protein binding). Although the efficacy of tramadol is comparable to that of other drugs with similar modes of action, the incidence of side effects such as constipation and respiratory depression is lower. The frequency of euphoria and dysphoria is negligible, resulting in little risk of abuse or dependence. It therefore seemed appropriate to further investigate the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain. Buprenorphine was selected as an opioid with a potency equivalent to half that of morphine, but with tolerability that is partially limited by the fact that it frequently gives rise to adverse reactions considered typical of stronger opioids. To compare the analgesic effect and tolerability of tramadol and buprenorphine, 60 patients (44 men, 16 women; average age 61.4 years), all presenting with advanced tumours, were treated orally in a controlled crossover trial with randomised sequences. Patients took both drugs, each for a week, with a 24-hour washout period between treatments. Tramadol was prescribed at the daily dose of 300mg, orally, and buprenorphine at 0.6 mg/day, as a sublingual preparation. Assessments were made of Karnofsky performance status and severity of pain before and during the 4 hours after taking the 2 drugs. Each patient also completed a daily diary recording the severity of pain 1 hour after the dose, the evolution of pain during the day and its severity compared with that on the previous day. They also assessed the duration and quality of sleep. The Karnofsky index changed little with either treatment, but all other variables showed worthwhile improvement, indicating the significant analgesic effect of both drugs. Buprenorphine and tramadol had a similar analgesic effect, although the improvement with the test drug was significant within 1 hour of administration (p < 0.05 compared with baseline) and more marked (p < 0.05 on day 2 compared with buprenorpine). At the end of tramadol treatment, sleep had also improved, both quantitatively and qualitatively (both p < 0.05). The final assessment was significantly in favour of tramadol as regards efficacy (p < 0.05) and patient acceptability (p < 0.01). Thus, tramadol was better tolerated than buprenorphine, and caused fewer and milder adverse reactions. Only 1 patient discontinued tramadol, compared with 18 using reference therapy. Tramadol, although theoretically less potent, nevertheless brought about as much pain relief as the comparator opioid. In conclusion, for this class of drug, tramadol provides an excellent balance between efficacy and tolerability, confirming preliminary studies.
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PMID:[Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine]. 919 Mar 24

The principal aim of palliative care is to bring symptomatic relief to patients with progressive disease. Residents graduating from a university general surgery training program should be competent to manage common symptoms associated with advanced cancer. This study used performance-based testing to evaluate the skills of resident physicians in managing common symptoms of a patient with advanced cancer. Thirty-three resident physicians (PGY 1 to 6) were presented with four clinical symptoms of a patient with advanced cancer: (1) nausea and vomiting associated with regular morphine use; (2) lack of appetite in the last weeks of life of a terminally ill patient; (3) constipation associated with codeine analgesia; and (4) dyspnea associated with diffuse lung metastases. The management plan for the symptom problems was evaluated by using a predefined checklist. A significant number of residents showed deficits in the management of common symptoms of advanced cancer. Scheduled dosing of antiemetics was infrequently prescribed for opioid-related nausea and vomiting. Most physicians inappropriately managed lack of appetite by using forced feeding. Opioids were infrequently used in the management of terminal dyspnea. The absence of difference in scores between junior and senior residents suggests that adequate management of the symptoms of terminal cancer is not being effectively taught in postgraduate training programs.
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PMID:Residents' management of the symptoms associated with terminal cancer. 925 84

Chronic treatment with opioids in cancer patients with chronic intestinal obstruction is hazardous, as uncontrolled constipation may result in definitive bowel obstruction. Intermittent use of opioids adjusted for fluctuating pain levels may enable patients to take the lowest opioid doses that will have sufficient effect, with a consequently lower risk of intestinal side effects. Methadone has many pharmacokinetic characteristics that fit it for use in this clinical situation. In two patients with recurrent episodes of bowel obstruction, methadone used at low doses and at flexible intervals regulated by the patients according to their pain level avoided the occurrence of new episodes of intestinal obstruction. Oral patient-controlled analgesia with methadone may be a simple, safe and cheap method of treating patients with pain associated with subtotal intestinal obstruction.
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PMID:Treatment of pain in chronic bowel subobstruction with self-administration of methadone. 925 31

Studies of analgesia in cancer patients have revealed that intrathecal administration of opioids can deliver potent analgesia with fewer systemic side effects than equivalent doses of systemic opioids. In addition, several trials have examined the safety and efficacy of this modality in patients with pain of nonmalignant origin. In one survey of 35 physicians involving 429 patients treated with intrathecal therapy, physician reports of global pain relief scores were excellent in 52.4% of patients, good in 42.9%, and poor in 4.8%. In another study of 120 patients, the mean pain intensity score had fallen from 93.6 to 30.5 six months after initiation of therapy. In both studies, patients reported significant improvement in activities of daily living, quality of life measures, and satisfaction with the therapy. Constipation, urinary retention, nausea, vomiting, and pruritus are typical early adverse effects of intrathecal morphine and are readily managed symptomatically. Other potential adverse effects include amenorrhea, loss of libido, edema, respiratory depression, and technical issues with the intrathecal system.
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PMID:Clinical realities and economic considerations: efficacy of intrathecal pain therapy. 929 7

Controlled-release (CR) formulations of oxycodone and morphine were compared in 45 patients with chronic cancer pain. The study was started with an open-label, randomised titration phase to achieve stable pain control for at least 48 h, followed by a double-blind, randomised, crossover phase in two periods, 3-6 days each. To blind the study using available tablet strengths, the dose ratio of oxycodone to morphine was set at 2:3. A daily telephone contact was maintained between the patient and the investigator. The patients were asked to assess pain intensity four times a day and acceptability of therapy twice daily, and to record possible adverse effects. Pharmacodynamic evaluations were performed at the end of each double-blind period. The patients were allowed to use escape analgesic (respective opioid as oral solution) as needed. Twenty-seven patients were evaluable for both safety and efficacy. Pain was well-controlled during both stable phases. When the period effect was taken into account the two opioids provided comparable analgesia. If the results of the two periods were combined, the patients consumed significantly more escape doses and the mean pain intensities were significantly greater with CR oxycodone. The total opioid consumption ratio of oxycodone to morphine was 2:3 when oxycodone was administered first, and 3:4 when oxycodone was administered after morphine. The total incidence of adverse experiences reported by the patients was similar, but significantly more vomiting occurred with morphine, whereas constipation was more common with oxycodone.
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PMID:Controlled-release oxycodone and morphine in cancer related pain. 941 55

Recent reports commissioned by the Australian Government have highlighted the need to improve medication use in both community and hospital settings. Nurses are placed ideally to promote safe and effective drug use. The aim of this project was to develop and evaluate a computer-assisted instruction package, to help undergraduate nursing students improve their knowledge of clinical pharmacology, and to enhance their ability to contribute to the quality use of medications. In a collaborative project, staff of the Tasmanian Schools of Pharmacy and Nursing have produced the program PharmaCAL, using HyperCard 2.2 for the Apple Macintosh. A wide range of clinical pharmacology units are covered extensively, concentrating on drugs in common use and based on body systems: cardiovascular pharmacology (including hypertension, cardiac failure and angina); respiratory pharmacology; alimentary tract pharmacology (including peptic ulcer, diarrhea, and constipation); central nervous system pharmacology (analgesia, anxiety and insomnia, depression, psychoses, and epilepsy); antibiotic chemotherapy; and diabetes mellitus. Many color illustrations have been included. Each unit has a set of multiple choice questions to provide feedback to students. The package was evaluated in two ways. First, a questionnaire was used to assess users' opinions of the package. Second, a validated multiple choice test on clinical pharmacology and therapeutics was administered to 24 third-year nursing students before and after a set of sessions using the package and to a control group of 28 nursing students who were not exposed to the PharmaCAL package. The package generally was well received by the nursing students. Clinical pharmacology test scores significantly improved after using the package and were significantly higher than for the control group of students. The program is a useful adjunct to the existing nursing curriculum. It also could be used in postgraduate nursing education and other health sciences.
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PMID:Development and evaluation of a computer-assisted instruction package in clinical pharmacology for nursing students. 945 93


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