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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrathecal drug delivery (IDD) is a proven and effective treatment alternative in carefully selected patients with chronic pain that cannot be controlled by a well-tailored drug regime and/or spinal cord stimulation (SCS), and may be specifically trialed in patients who fail to respond to SCS. While the lack of randomized controlled trials is often perceived as a limitation of IDD, many studies attest to the efficacy of this therapy, and a number are large-scale and with follow-up periods of up to five years. Good to excellent pain relief is achieved in many patients who have failed more conservative therapies, and there is often a reduced need for analgesia. The advent of patient-controlled analgesia allows flexibility of dosing according to the patient's needs. Consequently, quality of life improves in many patients and the majority express satisfaction with treatment. Some patients are able to return to work. The benefits of IDD (including a potent analgesic response with a more stable therapeutic drug level, decreased latency, increased duration of action, and decreased pharmacological complications) mean that side effects such as nausea, vomiting, sedation, and constipation are reduced. In addition, IDD demonstrates long-term cost-effectiveness when compared to conventional pain therapies, addressing a concern that affects many physicians in clinical practice today.
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PMID:Drug delivery systems. 1730 10

As a result of the undesired action of opioids on the gastrointestinal (GI) tract, patients receiving opioid medication for chronic pain often experience opioid-induced bowel dysfunction (OBD), the most common and debilitating symptom of which is constipation. Based on clinical experience and a comprehensive MEDLINE literature review, this paper provides the primary care physician with an overview of the prevalence, pathophysiology and burden of OBD. Patients with OBD suffer from a wide range of symptoms including constipation, decreased gastric emptying, abdominal cramping, spasm, bloating, delayed GI transit and the formation of hard dry stools. OBD can have a serious negative impact on quality of life (QoL) and the daily activities that patients feel able to perform. To relieve constipation associated with OBD, patients often use laxatives chronically (associated with risks) or alter/abandon their opioid medication, potentially sacrificing analgesia. Physicians should have greater appreciation of the prevalence, symptoms and burden of OBD. In light of the serious negative impact OBD can have on QoL, physicians should encourage dialogue with patients to facilitate optimal symptomatic management of the condition. There is a pressing need for new therapies that act upon the underlying mechanisms of OBD.
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PMID:Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. 1748 92

The ability of opioids to effectively and safely control acute and cancer pain has been one of several arguments used to support extending opioid treatment to patients with chronic pain, against a backdrop of considerable caution that has been based upon fears of addiction. Of course, opioids may cause addiction, but the "principle of balance" may justify that "...efforts to address abuse should not interfere with legitimate medical practice and patient care." Yet, situations are increasingly encountered in which opioid-maintained patients are refractory to analgesia during periods of pain, or even during the course of chronic treatment. The real question is whether analgesic efficacy of opioids can be maintained over time. Overall, the evidence supporting long-term analgesic efficacy is weak. The putative mechanisms for failed opioid analgesia may be related to tolerance or opioid-induced hyperalgesia. Advances in basic sciences may help in understanding these phenomena, but the question of whether long-term opioid treatment can improve patients' function or quality of life remains a broader issue. Opioid side effects are well known, but with chronic use, most (except constipation) subside. Still, side effects can negatively affect the outcomes and continuity of therapy. This paper addresses 1) what evidence supports the long-term utility of opioids for chronic pain; 2) how side effects may alter quality of life; 3) the nature of addiction and why it is different in pain patients, and 4) on what grounds could pain medication be denied? These questions are discussed in light of patients' rights, and warrant balancing particular responsibilities with risks. These are framed within the Hippocratic tradition of "producing good for the patient and protecting from harm," so as to enable 1) more informed clinical decision making, and 2) progress towards right use and utility of opioid treatment for chronic pain.
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PMID:Opioid analgesia: perspectives on right use and utility. 1752 83

Intravenous morphine is the treatment of choice for severe pain during vaso- occlusive crisis in sickle cell disease (SCD). However, side effects of morphine may hamper effective treatment, and high plasma levels of morphine are associated with severe complications such as acute chest syndrome. Furthermore, adequate dosing remains a problem since no objective measurement of pain severity exists and analgesia should be titrated upon the patient's reported pain. Patient-controlled analgesia (PCA) may therefore be an interesting alternative since patients can titrate the level of analgesia themselves. In this randomized controlled study, the efficacy of intravenous morphine administration with PCA was compared with continuous infusion (CI) of morphine in patients with SCD during vaso-occlusive crisis. Twenty five consecutive episodes of vaso-occlusive crisis in 19 patients with SCD were included in the study. Patients in the PCA-group had a markedly and significant lower mean and cumulative morphine consumption when compared with the patients in the CI-group (0.5 mg/hr versus 2.4 mg/hr (P < 0.001) and 33 mg versus 260 mg (P = 0.018, respectively). The mean daily pain scores were comparable (4.9 versus 5.3). The lower mean and cumulative morphine consumption in the PCA-group led to significant less nausea and constipation during treatment when compared with the CI-group (area under the curve, respectively, 11 versus 18 (P = 0.045) and 30 versus 45 (P = 0.021). Furthermore, a nonsignificant reduction in the duration of hospital admission of 3 days was observed in the PCA-group. PCA results in adequate pain relief at a much lower morphine consumption and should considered to be the first choice in morphine administration to sickle cell patients admitted with vaso-occlusive crisis.
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PMID:Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial. 1761 90

Gastrin and cholecystokinin (CCK) are two of the oldest hormones and within the past 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R and CCK2R), and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only a minor use of agonists. In this review, the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R and CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as to review their use in human conditions to date and the results. Despite extensive studies in animals and in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long-term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, and constipation) and pancreatitis (acute and chronic)].
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PMID:Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. 1799 37

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

Prolonged administration of morphine for the treatment of chronic pain causes constipation requiring the use of laxatives, which may result in electrolyte deficits. Morphine-induced constipation is due to the binding of the drug to opioid receptors in the gastrointestinal tract and the brain, where it mimics the actions of enkephalins. The effect on the gastrointestinal tract seems to be more intense than the central effect. The particular pharmacokinetic of naloxone makes it possible to reduce or abolish the constipation that follows oral administration of morphine without markedly interfering with the central effect of morphine, i.e. analgesia. The results obtained with oral administration to rats of morphine and naloxone in aqueous solution have already been published [17]. Oral morphine in doses of 1, 2.5 and 5 mg/kg reduce the intestinal transit time in a dose-dependent manner (Fig. 2, filled circles). Doses of 10 and 20 mg/kg are as effective as 5 mg/kg. Naloxone 10 mg/kg administered together with morphine either prevented or attenuated the constipating effect of morphine (Fig. 2, open circles). Tail-flick latency was used as an indicator of analgesia in the animal experiment; it was significantly increased 1, 2 and 3 h after oral administration of morphine 2.5 mg/kg (Fig. 3, hatched columns). When naloxone 10 mg/kg was given with the morphine, there was no significant reduction in tail-flick latency (Fig. 3, cross-hatched columns). Thus, oral administration of naloxone in aqueous solution antagonized the constipating effect of morphine without interfering with the antinociceptive effect of morphine. Experiments carried out with oral administration to rats of slow-release naloxone instead of naloxone in aqueous solution have not so far been published. Slow-release naloxone 5 mg/kg abolished the slowing of intestinal transit caused by oral morphine 2.5 mg/kg (Fig. 4, left-hand columns). The increase in transit time following morphine 5 mg/kg was deminished by simultaneous oral administration of slow-release naloxone 3 and 5 mg/kg in a dose-dependent manner (Fig. 4, right-hand columns). The increase in tail-flick latency caused by morphine 2.5 mg/kg was reduced but not abolished by simultaneous administration of naloxone 5 mg/kg (Fig. 5). Slow-release naloxone 3 or 5 mg/kg reduced the duration without interfering with the maximum of the antinociceptive effect of morphine 5 mg/kg (Fig. 6). These results show that slow-release naloxone is more effective than naloxone in aqueous solution in antagonizing the effects of morphine: after oral administration of the slow-release preparation, even the central action of morphine is reduced. Provided that the anatomical organization of the haemorrhoidal veins in the rat is similar to that in man, slow-release naloxone will be carried by the matrix, to which it is absorbed further down in the gastrointestinal tract. It may thus even reach the rectum, from where, after having been absorbed, it bypasses the liver, enters the central nervous system and reduces the antinociceptive effect of morphine. In conclusion, it can be stated that oral administration of naloxone in combination with morphine may help to prevent constipation during the treatment of chronic pain.
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PMID:[Oral administration of slow-release naloxone for prevention of constipation but not analgesia following oral morphine.]. 1841 96

Analgesic pharmacotherapy represents one of the major approaches to the treatment of cancer pain, since it is used in almost every patient. A thorough evaluation of the physical and mental status of the patient and of the pain is as necessary as a sound understanding of the pharmacokinetic and pharmacodynamic characteristics of the analgesics selected. The World Health Organization (WHO) has issued a basic 3 stage progression for the treatment of cancer pain, the "WHO Analgesic Ladder". Assignment to the stages depends mainly on the intensity of the pain rather than on its specific aetiology. Mild to moderate pain is treated with non-opioid drugs; moderate to severe pain, with a combination of a "weak" opioid and a non-opioid; and "strong" opioids should be used in combination with a non-opioid in the case of severe pain. Adjuvant drugs can be added if specifically indicated. Nonopioid analgesics include non-acidic compounds, e. g. paracetamol and metamizole, and acidic non-opioids, e. g. acetylsalicylic acid and newer non-steroidal anti-inflammatory drugs (NSAID). In contrast to most of the opioid analgesics, they have a ceiling effect for analgesia. Addiction and tolerance are extremely rare concerns. Opioids can be subgrouped into "weak" (e. g., codeine, dextropropoxyphene) and "strong" opioids (e. g., morphine) and also into drugs interacting with different opioid-receptor subtypes. Whereas pure agonists (e. g., morphine) produce increasingly intense analgesia with increasing dose, partial agonists and agonist-antagonists have a ceiling effect for analgesia and therefore have only a minor role in the treatment of chronic pain in cancer patients. Adverse effects occur in most patients in a dose-dependent manner. The most common of these is constipation; nausea, vomiting and sedation occur mostly at the start and can usually be treated effectively. The appropriate dosage, route of administration and dosage scheme of analgesics needs to be worked out for each individual patient in intensive work with the patient and a close follow-up, for years if necessary. Some analgesics may not be available in some countries, or only in specific preparations.
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PMID:[Drug therapy for tumor pain I. Properties of non-opioids and opioids.]. 1841 58

Adjuvant analgesics are drugs that are not primarily used as analgesics but can produce analgesia in certain types of pain. Adjuvant analgesics can be administered together with non-opioid and opioid analgesics on each step of the WHO analgesic ladder. They should be given when an additional or specific indication exists, but should not be used as a substitute for a thorough treatment with opioids and nonopioids. Adjuvant analgesics can be classified into groups according to the type of pain to be treated: continuous neuropathic pain or lancinating neuropathic pain, sympathetically maintained pain, bone pain and those for multipurpose use. Adjuvant drugs used for continuous neuropathic pain include local anaesthetics, clonidine, capsaicin, and antidepressants. Tricyclic antidepressants are the group that have been best investigated, and are therefore the drugs of choice. An analgesic effect is probably produced via enhancement of transmitter concentrations in pain-modulating pathways. This occurs at lower doses than those necessary to treat depression. Anticholinergic actions, acute glaucoma, constipation, orthostatic hypotension and cardiac arrhythmias are adverse effects that are seen predominantly with teritiary amine drugs and less often with secondary amine compounds. Initial doses should be small to avoid these adverse effects. Local anaesthetics are used less often, because of the high incidence of side effects (especially with tocainide, flecainide). An analgesic effect has been described in neuropathic pain, however, probably due to membrane stabilization and reduction of aberrant signal conduction. Mexiletine is considered to be the safest local anaesthetic, and should be used initially in small doses (100-150 mg/d). If side effects do not occur, doses can be increased step-wise up to 900 mg/d. Local anaesthetics are indicated for the treatment of severe neuropathic pain; this treatment is contraindicated in patients with cardiac arrhythmias. Systemic or intrathecal clonidine can be tried in neuropathic pain refractory to opioid therapy. The same stands for the topical application of capsaicin in certain types of pain. Lancinating neuropathic pain is an indication for anticonvulsant drugs. Carbamazepine, clonazepam, valproate and phenytoin seem to reduce aberrant signal conduction in damaged nerves in a manner similar to the supression of epileptiform activities in the brain. Common side effects include sedation, dizziness and nausea. Of greater concern are the more severe side effects, such as bone marrow depression (carbamazepine) and hepatotoxicity (phenytoin, valproate). Low initial doses and stepwise increases in dosage, repeated blood counts, and monitoring of plasma levels are helpful in recognizing and avoiding these adverse effects. Baclofen, a GABA agonist primarily used for spasticity, is effective in the treatment of trigeminal neuralgia and is often used in the management of lancinating pain of unspecific origin. The initial dosage is 10-15 mg/d, increasing to 30-90 mg/d, or higher. If neural blockade fails to reduce sympathetically maintained pain sufficiently specific adjuvants can be used. Sympatholytic drugs, e.g. phenoxybenzamine (60-120 mg/d) or prazosin, can be administered to patients without major cardiovascular dysfunction. There is experimental evidence of the involvement of calcium channels in nociception, and a beneficial clinical effect of nifidepine in reflex sympathetic dystrophy (RDS) has been demonstrated. Bone pain is common in tumor patients and can often be treated effectively with non-steroidal anti-inflammatory drugs. Biphosphonates (etidronate, clodronate, pamidronate derivates) also produce analgesic effects in patients with bone metastases. However, differences among the various compounds have not been clearly evaluated yet. Potent and specific radioisotopes are still under development and the use of calcitonin in bone pain is considered controversial.
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PMID:[Pharmacotherapy of cancer pain. 3. Adjuvant drugs.]. 1841 35

Introduction Buprenorphine is well known in cancer pain therapy because of the long duration of its action and high analgesic potency. Many studies exist about the intravenous and sublingual application form; however, few data are available on its use by the continuous subcutaneous route. Methods Twenty-five patients were analysed retrospectively over 956 days who has been treated with continuous subcutaneous buprenorphine for cancer-related pain. In 7 of these 25 patients plasma analyses were performed. Due to a modified sensitive HPLC method with electrochemical detection for the analysis of buprenorphine in plasma, a detection limit of 40 pg/ml could be obtained. The other analytical methods for plasma concentration have detection limits between 150 and 500 pg/ml. Results During the treatment with continuous subcutaneous buprenorphine it was necessary to increase the initial average daily dose of 1.07 (+/-0.41) mg to 1.58 (+/-0.58) mg. The initially high pain intensity (rated from 0 to 100%) of 67% could be reduced to a moderate pain of 26% on average. Only 2 patients had to be switched over to morphine because of insufficient analgesia. In no case did complications occur that required intervention or would have made it necessary to change the pain therapy. Eighty percent of the patients judged this kind of treatment as effective and comfortable. Most often patients complained about drowsiness, low appetite and constipation. Because of the progress of the cancer disease these effects could not clearly be related to treatment side effects. With 7 of 25 patients the median daily dose of 1.2 (minimum 0.9-maximum 2.3) mg buprenorphine was related to the median plasma concentration of 438 (minimum 64-maximum 3374) pg/ml. In one case with progressive liver dysfunction, the potential risk of cumulation with buprenorphine could be controlled with this method. Conclusions Continuous subcutaneous buprenorphine with external infusors is a safe and efficient cancer pain therapy without severe side effects. Because of its ceiling effect, it is not as effective as morphine, but can be discussed as an alternative if other opioids cause incompatibility reactions.
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PMID:[Continuous subcutaneous buprenorphine application in the treatment of cancer pain.]. 1841 45


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