Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of severe opioid toxicity is described in a 52-year-old cancer patient. The patient presented with classical clinical features of central hyperexcitability associated with opioid toxicity: delirium, myoclonus, hallucinations, hyperalgesia, and a possible seizure. This patient had a background of severe psychosocial distress and somatization in addition to a history of benzodiazepine dependence and alcohol abuse. The occurrence of opioid toxicity in this patient highlights the risks of a unidimensional approach to cancer pain, which ignores the non-organic components of pain, such as psychosocial distress, which will not respond to escalating doses of opioid medication.
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PMID:Severe opioid toxicity and somatization of psychosocial distress in a cancer patient with a background of chemical dependence. 920 57

The majority of cancer patients develop pain before death. This pain has been shown to be underdiagnosed and undertreated. Opioid use has increased in the past 20 years in both developing and developed countries. The changing pattern in opioid use has resulted in the emergence of neurotoxicity as a major side effect of the treatment of cancer pain. The syndrome of opioid-induced neurotoxicity (OIN) encompasses delirium, hallucinosis, myoclonus/seizures and hyperalgesia. Increased vigilance can lead to the timely diagnosis of OIN, and strategies for its treatment can be implemented with encouraging results. Identification and modification of risk factors for the development of OIN can help in its prevention and improve the quality of life in advanced cancer patients.
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PMID:Opioid use in cancer pain. Is a more liberal approach enhancing toxicity? 1052 40

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

Cancer pain management is expected to become more important because of the growing number of cancer patients in the years to come. To improve cancer pain relief requires understanding and adequate application of the WHO three-step analgesic ladder. Selective cox-2 inhibitors have efficacy in decreasing side effects. Tramadol and a new type of transdermal fentanyl patch that provides 24-hour sustained release of fentanyl is commercially available to alleviate pain. New anti-seizure drugs such as Gabapentin and Pregabalin can be used for neuropathic pain and cancer pain as analgesic adjuvant drugs. They allow simple use than with palliative drugs so far. Palliation of cancer pain requires a multi-discipline approach for intensive management of symptoms.
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PMID:[Pain management in cancer patients]. 2094 46

Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions. Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008. Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.
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PMID:Endocannabinoid System: A Multi-Facet Therapeutic Target. 2708 1

The management of cancer pain still poses a major challenge for clinicians. Tramadol is a centrally acting synthetic opioid analgesic. Its well-known side effects include nausea, vomiting, and dizziness; seizures are a rare side effect. Some reports have found that tramadol triggers seizure activity at high doses, whereas a few preclinical studies have found that this seizure activity is not dose-related. We herein present a case involving a patient with laryngeal cancer who developed seizures while on low-dose oral tramadol.
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PMID:Seizures associated with low-dose tramadol for chronic pain treatment. 2721 78

The significance of continuous subcutaneous injection(CSI)therapy was assessed in end-of-life symptoms of cancer and non-cancer home hospice patients. In a retrospective analysis of 106 advanced cancer patients who underwent opioid CSI therapy, the most frequent symptom was pain(65%), followed by dyspnea(46%), seizure(8%), ileus(8%), and other uncontrolled end-of-life symptoms(23%). The median oral morphine equivalent daily opioid dose was 90 mg(2.5-1,920 mg)and the median duration of CSI administration was 3 days(1-350 days). Eighty-six percent of the patients underwent adjunct therapy to opioids, such as midazolam, octreotide, and haloperidol, in the management of cancer pain and non-pain cancer symptoms. In 5 non-cancer patients with systemic vascular disease, various symptoms required opioid CSI in the endof- life days. CSI with adjunct therapy to opioids can be effective in the treatment of end-of-life symptoms in both cancer and non-cancer patients.
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PMID:[Continuous Subcutaneous Injection Therapy in End-of-Life Symptoms of Cancer and Non-Cancer Patients]. 2965 Aug 92