Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
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Potent opioids are excellent painkillers but their use is hampered by side-effects such as nausea, vomiting, bowel dysfunction, urinary retention, pruritus, sedation and respiratory depression. Co-analgesics are often combined with opioids to reduce the prevalence of these unwanted effects while maintaining or even improve the quality of analgesia. A search of the recent literature demonstrated that peripheral opioid antagonists are able to reduce opioid-induced bowel dysfunction without interfering with analgesia. Dexmedetomidine, gabapentin, and ketamine significantly reduce opioid consumption but have no effect on the incidence of opioid side-effects. In contrast, intravenous lidocaine and corticosteroids not only produce an opioid-sparing but also a significant reduction in the occurrence of postoperative ileus and nausea and vomiting. It remains unclear whether the perioperative use gabapentin, ketamine and corticosteroids has an effect on the development of postsurgical chronic pain states.
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PMID:Systemic analgesia and co-analgesia. 1691 80

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

Simultaneous use of opioids with a different pharmacological profile during anesthesia may lead to unexpected prolongation of effects. In addition, long-term use of transdermal buprenorphine may result in a reduced sensitivity to opioid anesthesia. In a prospective study, possible overlap of opioid effects and vigilance was determined in a group of patients (n = 22) using a buprenorphine patch for at least two months for treatment of chronic pain, and undergoing fentanyl-based fast-track enflurane anesthesia for open-heart surgery. The patients using buprenorphine were compared with a control group (n = 21) undergoing similar open-heart procedures with no opioid other than fentanyl on board. Aside from time to extubation, total dose of fentanyl, postoperative blood gases, and vigilance assessment score were used to determine possible overlap of opioid effects and/or development of opioid tolerance in the buprenorphine group compared to the control group. Both groups had similar operation and anesthesia times and comparable doses of fentanyl (0.69 mg +/- 0.23 vs. 0.67 mg +/- 0.16 SD). There was no significant difference in postoperative arterial blood gases (PaO2 136 +/- 48 torr vs. 128 +/- 35 torr SD; PCO2 43.3 +/- 3.3 torr vs. 41.9 +/- 1.2 torr SD), time until extubation (27 +/- 22 min vs. 33 +/- 24 min), and postanesthetic vigilance and recovery score (6.8 +/- 1.0 vs. 7.5 +/- 0.8, arbitrary units) between the two groups. Because of adaptive mechanisms and the development of tolerance in patients using buprenorphine, respiratory depression or sedation does not project into the postoperative period. The significant (p < 0.05) lower incidence of nausea and emesis in patients with transdermal buprenorphine owes to the development of tolerance to these opioid-related side effects.
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PMID:No potentiation of fentanyl by use of transdermal buprenorphine in patients undergoing fast-track anesthesia for open-heart surgery. 1731 20

The ability of the somatosensory system to detect noxious and potentially tissue-damaging stimuli is an important protective mechanism, that involves multiple interacting peripheral and central mechanisms. The postoperative pain is related with surgical procedure irrevocable. The effective relief of pain is of paramount importance to anyone treating patients undergoing surgery. This should be achieved for humanitarian reasons, but there is now evidence that pain relief has significant physiological benefit. Not only does effective pain relief mean a smoother postoperative course with earlier discharge from hospital, but it may also reduce the onset of chronic pain syndromes. Pain causes an increase in the sympathetic response of the body with subsequent rises in heart rate, cardiac work and oxygen consumption. Prolonged pain can reduce physical activity and lead to venous stasis and an increased risk of deep vein thrombosis and consequent pulmonary embolism. In addition, there can be widespread effects on gut and urinary tract motility which may lead, in turn, to postoperative ileus, nausea, vomiting and urinary retention. These problems are unpleasant for the patient and may prolong hospital stay. Choice of technique will also be influenced by the degree of training and expertise of the staff. The choice of pain-relieving techniques may be influenced by the site of surgery.
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PMID:[Postoperative pain therapy in otolaryngological department]. 1734 25

Acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting and for postoperative dental pain. Several recent randomized trials have provided strong evidence for beneficial AP effects on chronic low-back pain and pain from knee osteoarthritis. For many other chronic pain conditions, including headaches, neck pain, and fibromyalgia, the evidence supporting AP's efficacy is less convincing. AP's effects on experimental pain appear to be mediated by analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes considerable time to develop and to resolve. Thus, some of the long-term effects of AP analgesia cannot be explained by placebo mechanisms. Furthermore, it appears that some forms of AP are more effective for providing analgesia than others. Particularly, electro-AP seems best to activate powerful opioid and non-opioid analgesic mechanisms.
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PMID:Mechanisms of acupuncture analgesia: effective therapy for musculoskeletal pain? 1817 1

Oral medication is the simplest way in treatment of chronic pain. For cancer pain oral analgesics are efficacious in more than 90% of the patients. When a causal therapy of pain (e.g. chemotherapy, operation) fails an analgesic ladder with oral analgesics is instituted. This ladder starts with a non-narcotic analgesic in a sufficient dose. The regular dose of acetylsalicylic acid or paracetamol is 4 g daily. When this dose does not work sufficiently, a weak opioid (e.g. dihydrocodeine) is given concomitantly at an individual dose. When the weak opioid fails, strong opioids are given (e.g. morphine). The drugs should be given by mouth whenever possible. The most important point is the regular application according to a time-schedule. This time-schedule is related to the action time of the drug. Patients with severe vomiting or dysphagia can receive a continuous subcutaneous infusion. These measures are based on recommendations of the WHO.The same medications can be employed in patients with chronic non-malignant pain, provided that all other conventional measures in pain treatment fail. However, many states of pain are not opioid-responsive. Pain related to the sympathetic nervous system is more responsive to antidepressants than to opioids or NSAID. Neuropathic pain as in trigeminal neuralgia responds to anticonvulsants. Pain from muscle spasm is better controlled by muscle relaxants than by analgesics. Bone pain is more sensitive to NSAID than to any other drug.In any state of pain the response to the different groups of drugs should be evaluated first. Then a stepwise pharmacological approach should be performed. In most cases pain can be treated effectively by oral drugs.
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PMID:[Not Available]. 1841 67

Up to 70% of cancer patients in the terminal phase of their disease complain of moderate or severe pain. Pain therapy in these patients follows the analgesic ladder of the WHO. Many cancer patients will need a strong opioid to get sufficient pain relief. Fentanyl-TTS (transdermal therapeutic system) may be a new alternative for chronic pain therapy in cancer patients. Analgesic rates of fentanyl are released from the patch over a period of 72 h. After application, peak serum concentrations of fentanyl are measured after 8-16 h. Serum half-life time is prolonged (16-21 h) because of the intradermal depot of fentanyl. The efficacy of Fentanyl-TTS in pain therapy for cancer patients was demonstrated in clinical studies, which showed a good analgesic effect over a long period of time. Like the chronic therapy of cancer pain with conventional opioid routes, dose escalation was necessary in most patients. In most studies the application of another opioid in a second route of application was necessary as a rescue medication. During therapy of cancer pain with Fentanyl-TTS, 3 of 246 patients developed a bradypnea (respiratory rate <10/min). In contrast, respiratory depression in chronic cancer pain was never reported when the opioid was administered orally or regionally and when technical faults were excluded. The side effects during therapy with Fentanyl-TTS were those accompanying chronic opioid therapy (constipation, vomiting, nausea). The patch was well tolerated by the skin. Local side effects were minor (erythema, pruritus, pustules) and disappeared within a few hours after removal of the patch. The transdermal application of a strong opioid may be an alternative, especially for patients with cancer of the head and neck or in the gastrointestinal tract. Because of the pharmacokinetic laziness of the system the use of Fentanyl-TTS should be limited to patients with stable tumor pain. In these patients Fentanyl-TTS might be valuabe on step III of the analgesic ladder of the WHO or as an alternative to invasive methods when it is impossible to administer oral opioids.
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PMID:[Transdermal fentanyl for the treatment of cancer pain.]. 1841 15

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

Chronic pain requires chronic treatment. Dihydrocodeine retard (DHC) complies with the requirements for treatment of chronic pain: its sustained release formula provides pain relief for up to 12 h. Thus, taking two tablets of this preparation daily is sufficient to ensure continuous pain relief. Patients and methods The 309 physicians participating in the study treated a total of 1502 patients and provided more than 5000 reports containing data on pain relief and side effects. Treatment was performed according to the WHO principles for the analgesic treatment of cancer pain patients, i.e., doctors and patients were taught that two tablets are taken per day, one in the morning and one in the evening, irrespective of whether pain was present or not. Most of the data were derived from the first 4 weeks of treatment. Patients were selected at random. All had chronic pain, but the diagnosis was not a selection criterion. The patients had had prior treatment with various analgesic regimens, and in most cases drugs were administered at irregular intervals, i.e., on demand. About half of the patients (54%) suffered from pain related to the musculoskeletal system such as back pain, joint pain, polyarthritis. Twenty-four percent had cancer pain and 22% had pain caused by other sources, mostly neuropathic pain, including cases of severe postherpetic neuralgia. Most of the patients were older than 50 years; the average age in the patient population was 62 years. There were 816 women and 686 men. Patients assessment of analgesic treatment was performed before starting therapy with DHC (thus conferring to prior therapy) and after 1 and 2 weeks of treatment with the new drug. While only about 10% of the patients found their prior pain treatment excellent or good, nearly 80% rated the treatment with DHC as excellent or good and only 2% as bad.Severity of pain was assessed by the patients on a four-step verbal rating scale ranging from "no or little pain" to "extremely strong pain". At the time of admission to this post-marketing surveillance 51.5% of the patients suffered from very strong pain and 41% reported strong pain. Five percent had extremely strong pain and only 2.1% reported no or little pain. After 2 weeks of treatment with DHC, 54.5% had little or no pain, 29% suffered from strong pain, 7% from very strong, and 0.4% from extremely strong pain.Sleeping problems are known to be reported by patients with chronic pain. They often cannot sleep continuously for more than a few hours. Thus, the effect of DHC on sleep was evaluated. Before starting the new treatment only 8% of the patients were having uninterrupted sleep for 6 h or more, and more than 50% of the patients slept less than 3 h. During treatment with DHC 48% of the patients had more than 6 h of uninterrupted sleep and about 82% slept continuously for more than 3 h per night. Side effects About 20% of patients reported nausea at baseline (during previous treatment); vomiting was reported in 7.6%. These percentages did not change during the first week of treatment with sustained-release DHC and even decreased slowly during the next 3 weeks. The frequency of constipation increased from 14% at baseline to about 29.5% at the end of the second week of treatment with DHC with no change during the next four weeks. A total of 312 side effects were mentioned in 5308 reports delivered by the 1502 patients during the treatment with DHC (including multiple reports). The most frequent side effects were gastrointestinal (n=106), followed by symptoms related to the central nervous system such as dizziness, sedation, etc. (n=50), and non-specific symptoms such as indisposition (n=29). Other specific symptoms were rare and distributed over many different organ systems. Insummary, the findings of this post marketing surveillance study suggest that sustained-release dihydrocodeine is an effective and safe analgesic drug for the treatment of chronic pain of various causes.
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PMID:[Pain treatment with dihydrocodeine slow release. Results of a post marketing surveillance study.]. 1841 87

Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.
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PMID:Opioid complications and side effects. 1844 35


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