Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a report about five anaesthetic techniques for laparoscopy. Propofol and etomidate were used for total intravenous anaesthesia. Propofol, etomidate and thiopentone were used as induction agents prior to inhalational anaesthesia with isoflurane and nitrous oxide. Fentanyl was used for analgesia. Induction with propofol and thiopentone was rapid. Etomidate induction was characterised by myoclonus. Maintenance was smooth with inhalational anaesthesia. Of the groups that received total intravenous anaesthesia, propofol provided stable anaesthesia but required extra bolus doses. Recovery was the most rapid following total intravenous anaesthesia with propofol. Postoperative side effects were much lower after propofol. No difference was observed between the groups with regard to changes in arterial blood pressure and heart rate.
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PMID:Anaesthesia for laparoscopy. A comparison of five techniques including propofol, etomidate, thiopentone and isoflurane. 295 68

Thirty-nine unpremedicated patients who presented for cystoscopy were given either alfentanil or saline in a random double-blind fashion immediately before anaesthesia with etomidate, nitrous oxide and enflurane. Alfentanil significantly reduced myoclonus associated with etomidate. During anaesthesia, patients who received alfentanil had smaller minute volumes, lower respiratory frequencies, and smaller increases in heart rate. The incidence of apnoea was not significantly increased. After operation, patients who received alfentanil were prescribed significantly more analgesia, possibly because of their reduced uptake of volatile anaesthetic agent. It is concluded that supplementation with alfentanil improves the quality of anaesthesia induced with etomidate.
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PMID:Alfentanil supplemented anaesthesia for short procedures. A double-blind study of alfentanil used with etomidate and enflurane for day cases. 308 48

The active morphine metabolite, morphine-6-glucuronide (M-6-G), may contribute to both the analgesia and the adverse effects observed during morphine (MOR) therapy. To evaluate the relationship between M-6-G and adverse effects, we measured steady-state plasma concentrations of MOR and M-6-G and concurrently noted the presence or absence of moderate to severe cognitive impairment or myoclonus in 109 cancer patients who were receiving either oral (n = 71) or parenteral (n = 38) morphine. MOR and M-6-G plasma concentrations were determined by HPLC with electrochemical detection. The presence of cognitive impairment or myoclonus was analyzed in relation to molar M-6-G/MOR ratio, age, morphine dose, the use of other centrally acting drugs, renal function (blood urea nitrogen (BUN) and serum creatinine), hepatic function (serum bilirubin, serum glutamic oxalacetic transaminase (SGOT), and alkaline phosphotase) and serum lactate dehydrogenase (LDH). The patient population consisted of 60 women and 49 men. The mean age was 51.5 years (range: 10-85 years). The mean morphine dose (total dose-prior 48 h) was 486 mg (range: 40-4800 mg) for the oral group and 931 mg (range: (10-9062 mg) for the parenteral group. The mean molar M-6-G/MOR ratios were 6.1 (SD: 18.2; range: 0.01-153.3) for the oral treatment group and 2.7 (SD: 4.16; range: 0.05-23.8) for the parenteral treatment group. Overall, the M-6-G/MOR ratio demonstrated a moderate but significant correlation with BUN (r = 0.4; P < 0.001) and creatinine (r = 0.45; P < 0.001) levels, but not with the other clinical variables examined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients. 764 48

Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long-term treatment of severe pain. Morphine is a member of the morphinan-framed alkaloids, which are present in the poppy plant. The drug is soluble in water, but its solubility in lipids is poor. In man, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to compete for opioid receptor binding. The analgesic properties of M6G were recognised in the early 1970s and more recent work suggests that M6G might significantly contribute to the opioid analgesia after administration of morphine. The analgesic potency of M6G after intracerebroventricular (ICV) or intrathecal (IT) administration in rats is from 45-800 timer greater than that of morphine, depending on the animal species and the experimental antinociceptive test used. Furthermore, the development of a sensitive high-performance liquid chromatography (HPLC) assay for the quantitative determination of morphine, M6G and M3G has revealed that M6G and M3G were present in abundance after chronic oral morphine administration and that the area under the plasma concentration-time curve exceeded that of morphine. M3G has been found to antagonise morphine and M6G induced analgesia and ventilatory depression in the rat, which has led to the hypothesis that M3G may influence the development of morphine tolerance. M3G exhibits no analgesic effect after ICV or IT administration. Some studies do, however, indicate that M3G may cause non-opioid mediated hyperalgesia/allodynia and convulsions after IT administration in rats. These observations led to the hypothesis that M3G might be responsible for side-effects, hyperalgesia/allodynia and myoclonus seen after high-dose morphine treatment.
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PMID:Morphine metabolites. 906 Oct 94

With the increasing use of morphine, growing interest for the clinical implications of its metabolites, morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) has emerged in the literature. M-6-G binds to the opioid receptor and has analgesic properties in man. Clinical studies have not delivered strong evidence of significant correlation between the concentration of morphine and its glucuronides in plasma and cerebrospinal fluid and pharmacodynamics such as analgesia. There is no clinical evidence to indicate that M-6-G has a pronounced respiratory depressing effect in man, while the literature contains conflicting reports with regard to other side-effects. M-3-G does not bind to the m-opioid receptor and consequently has no antinociceptive effects. Studies in rodents have shown that morphine, M-6-G and especially M-3-G may induce hyperalgesia, allodynia and myoclonus. It is assumed that these side effects are caused by a spinal antiglycinergic mechanism. The role of M-3-G in morphine antagonism and development of tolerance has not yet been settled. As M-3-G and M-6-G are eliminated by the kidneys, renal insufficiency will lead to accumulation of these. Accordingly dosage should be reduced or other opioids be considered in such cases.
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PMID:[Morphine metabolism--pharmacokinetics and pharmacodynamics]. 919 24

Myoclonus occasionally occurs in the perioperative setting and in patients on chronic opioid therapy. It appears to be dose-related in a unpredictable manner. Different mechanisms have been proposed to explain the occurrence of a series of neuromuscular disturbances probably sharing final common pathways. A neuroexcitatory opioid metabolite accumulation has been proposed to have a relevant role in determining myoclonus in patients treated with chronic opioid therapy for cancer pain, especially in the presence of renal impairment. The neurological status, previous oncologic treatment and concomitant therapy with neuroleptic drugs, the metabolic and hydration status should also have been considered. Adjuvant drugs, such as benzodiazepines or dantrolene may avoid the reduction of the opioid dose while maintaining an acceptable analgesia. Current practice suggests a change in opioid when pain control is not obtained at opioid doses resulting in unacceptable adverse effects, including myoclonus and hyperalgesia. A change in the type of opioid may be useful in patients who develop severe central adverse effects, even if these patients appear to have normal renal function or hydration status.
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PMID:Pathophysiology and treatment of opioid-related myoclonus in cancer patients. 951 54

1. Morphine is recommended by the World Health Organization as the drug of choice for the management of moderate to severe cancer pain. 2. Education of health professionals in the past decade has resulted in a large increase in the prescribing of opioids, such as morphine, and in the magnitude of the doses administered, resulting in an improvement in the quality of pain relief available for many cancer patients. 3. However, the reported incidence of neuroexcitatory side effects (allodynia, myoclonus, seizures) in patients administered large doses of systemic morphine or its structural analogue, hydromorphone (HMOR), has also increased. 4. Clinically, increasing the magnitude of the morphine or HMOR dose administered to patients already exhibiting neuroexcitatory opioid related side effects, results in an exacerbation rather than an attenuation of the excitatory behaviours. 5. In contrast, cessation of the opioid or rotation to a structurally dissimilar opioid (e.g. from morphine/HMOR to methadone or fentanyl), usually results in a restoration of analgesia and resolution of the neuroexcitatory opioid side effects over a period of hours to days. 6. To explain the clinical success of 'opioid rotation', it is essential to understand the in vivo metabolic fate of morphine and HMOR. 7. Following systemic administration, morphine and HMOR are metabolized primarily to the corresponding 3-glucuronide metabolites, morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G), which are not only devoid of analgesic activity but evoke a range of dose-dependent excitatory behaviours, including allodynia, myoclonus and seizures, following intracerebroventricular (i.c.v.) administration to rats. 8. Several studies have shown that, following chronic oral or subcutaneous morphine administration to patients with cancer pain, the cerebrospinal fluid (CSF) concentrations of M3G exceed those of morphine and morphine-6-glucuronide (analgesically active morphine metabolite) by approximately two- and five-fold, respectively. 9. These findings suggest that when the M3G concentration (or H3G by analogy) in the CSF exceeds the neuroexcitatory threshold, excitatory behaviours will be evoked in patients. 10. Thus, rotation of the opioid from morphine/HMOR to a structurally dissimilar opioid, such as methadone or fentanyl, will allow clearance of M3G/H3G from the patient central nervous system over hours to days, thereby producing a time-dependent resolution of the neuroexcitatory behaviours while maintaining analgesia with methadone or fentanyl.
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PMID:Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. 1087 11

The nurse administering any BZD--especially lorazepam--to a neonate must be knowledgeable about the drug's effects and risks and must remember that BZDs do not provide analgesia. The sedative effects of lorazepam will increase with concomitant use of opioids. The nurse must be alert for adverse reactions (Table 1). Close monitoring of the neonate's respiratory effort and blood pressure is important. Because of the various reported cases of myoclonus in neonates after lorazepam administration, close observation for seizure activity is imperative. Although lorazepam use may be beneficial in specific instances, administration should be approached with caution in the neonate (especially in the preterm neonate) and other agents considered.
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PMID:Lorazepam. 1194 76

We report 3 cases of myoclonus associated with etomidate during ED procedural sedation and analgesia (PSA). EPs should be familiar with myoclonus associated with etomidate. Clinicians using this drug for PSA should be prepared to offer the brief period of support, and occasionally, respiratory assistance, required when etomidate-associated myoclonus is encountered.
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PMID:Myoclonus associated with etomidate for ED procedural sedation and analgesia. 1465 36

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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