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)

This paper is the twenty-first installment of our annual review of research concerning the opiate system. It summarizes papers published during 1998 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.
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PMID:Endogenous opiates: 1998. 1069 31

Expert and aggressive pre-operative preparation of the woman with severe pre-eclampsia will ultimately determine her intraoperative outcome. Such considerations as the effect of endotracheal manipulation on intracranial pressure, of thrombocytopenia on the potential to produce a compressive epidural haematoma following epidural or combined spinal-epidural neuraxial block and of adequacy of invasive monitoring for Caesarean section loom large in the eyes of an anaesthetist preparing such a patient for surgery. Time spent pre-operatively in fluid volume optimization, in assessment of ventricular function, filling pressures and systemic vascular resistance, on aspiration pneumonitis and seizure prophylaxis, on control of hypertension, on correction of coagulopathy and on attenuation of pressor responses is time well spent and will have profound effects on the peri-operative course. The choice of agents and techniques for control of hypertension and reduction of vascular resistance, for induction and maintenance of general anaesthesia, for eclampsia prophylaxis and for regional anaesthesia or analgesia for operative or spontaneous delivery is, likewise, important and, at times, problematic.
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PMID:Clinical management of established pre-eclampsia and gestational hypertension: an anaesthetist's perspective. 1074 95

Pyrilene acts as a central H-cholinoblocker upon intramuscular injection at a dose of 0.02-0.08 mg/kg, and as an NMDA-blocker, when the dose is increased to 0.2-0.8 mg/kg. Similarly, amantadine exhibits the properties of H-cholinoblocker and NMDA-blocker in the dose intervals 10-15 mg/kg and 120-180 mg/kg, respectively. The activity of MK-801 markedly exceeds that of memantine, although close doses of both NMDA-blockers inhibit the NMDA and corazole effects, as well as the central effects (analgesia and seizure) of nicotine, thus showing no significant selectivity with respect to NMDA. IEM-1754 tested on intact animals exhibited a selective action upon the NMDA receptors, preventing the NMDA-induced analgesia and lethality and the corazole-induced convulsions at doses 10-100 times lower as compared to those preventing nicotine-induced seizure and analgesia.
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PMID:[A comparative study of the central H-cholinergic-blocking and NMDA-blocking actions of MK-801, memantin, amantadine, pyrilen and IEM-1754 in experiments on intact rats]. 1083 88

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

Severe falciparum malaria, with its associated hyperpyrexia, distorts plasma levels of large neutral amino acids (NAA) and consequently, brain uptake of individual NAA. Since brain levels of NAA determine cerebral synthesis of monoamines (serotonin, histamine, catecholamines), we measured plasma concentrations of NAA, and also plasma histamine (Hm) in children with falciparum malaria and in uninfected controls. Malaria elicited a marked (P < 0.025) increase in plasma histidine (His) with a 5-fold significant (P < 0.001) elevation in histamine, as well as a 2.5-fold increase (P < 0.005) in plasma phenylalanine (Phe), with no changes in the other NAA. Using kinetic parameters of NAA transport at human blood-brain barrier (BBB), we showed that malaria significantly altered calculated brain uptake of His (+30%), Phe (+96%), Trp (-30%) and Ile (-27%), with no change in the other NAA, compared with controls. Our data suggested enhanced cerebral synthesis of Hm with impaired production of serotonin and the catecholamines in the patients, and therefore, the need to evaluate the encephalopathy in severe malaria within the context of abnormalities in metabolism of Hm and other monoamines resulting from imbalance in plasma levels of the large neutral amino acids. Of clinical relevance also is the impaired inactivation of increased brain Hm by antimalarials such as the widely used aminoisoquinolines leading to elevated brain levels of imidazole-4-acetic acid (IAA), a potent inducer of a sleep-like state often accompanied by seizures, analgesia, decreased blood pressure and other effects.
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PMID:Increased plasma levels of histidine and histamine in falciparum malaria: relevance to severity of infection. 1114 3

The neural mechanisms involved in post-ictal analgesia remain to be elucidated. Pentylenetetrazol (PTZ) is used experimentally to induce seizure in animal subjects. This non-competitive antagonist blocks GABA-mediated Cl(-) flux. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significant increase in the tail-flick latencies (TFL), at least for 30 min of the post-ictal period. Peripheral administration of naloxone (5 mg/kg and 10 mg/kg), atropine (1 mg/kg and 5 mg/kg), methysergide (1 mg/kg and 5 mg/kg) and ketanserine (1 mg/kg and 2 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. However, while naloxone antagonized analgesia 15 and 25 min post convulsions, the other drugs caused a blockade of the post-ictal analgesia in a relatively greater period of time. These results indicate that endogenous opioids, serotonin and acetylcholine may be involved in post-ictal analgesia.
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PMID:Post-ictal analgesia: involvement of opioid, serotoninergic and cholinergic mechanisms. 1115 Apr 91

This paper is the twenty-second installment of the annual review of research concerning the opiate system. It summarizes papers published during 1999 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunologic responses.
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PMID:Endogenous opiates: 1999. 1115 Jun 56

We report a case of intracerebral haemorrhages associated with continuous spinal analgesia. Continuous spinal analgesia is frequently employed for postoperative analgesia in high-risk patients in our institution. The analgesia is administered via a 20 gauge catheter passed through an 18 gauge Tuohy needle (Portex). A 71-year-old man with severe respiratory impairment had an intrathecal catheter placed for postoperative analgesia. He had a difficult postoperative course, including wound dehiscence, and died from respiratory failure some five weeks postoperatively. On day nine postoperatively he had two tonic-clonic seizures and was subsequently found to have developed bilateral frontal intracerebral haemorrhages. There was no previous history of seizures. Although several confounding variables exist, the most likely explanation for the intracerebral event appears to be an association with the dural puncture and intrathecal catheter Possible mechanisms and risk factors are discussed.
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PMID:Bilateral frontal haemorrhages associated with continuous spinal analgesia. 1126 12

Adenosine is a modulator that has a pervasive and generally inhibitory effect on neuronal activity. Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors. Relief from this tonic inhibition by receptor antagonists such as caffeine accounts for the excitatory actions of these agents. Characterization of the effects of adenosine receptor agonists and antagonists has led to numerous hypotheses concerning the role of this nucleoside. Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use.
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PMID:The role and regulation of adenosine in the central nervous system. 1128 4

Tramadol is an option for the treatment of rheumatological pain. Its mode of action and safety profile distinguishes it from other opioids. Tramadol differs from other opioids by combining a weak opioid and a monoaminergic mode of action. It is effective in different types of moderate-to-severe pain, including neuropathic pain. Moreover, as the mode of action of tramadol does not overlap with that of NSAIDs, it is a useful agent to be combined with these drugs. Tramadol induces fewer opioid adverse reactions for a given level of analgesia compared with traditional opioids. Common adverse reactions of tramadol such as nausea and dizziness, which usually occur only at the beginning of therapy and attenuate over time, can be further minimized by up-titrating the drug over several days. Dose adjustment is only necessary in patients over 75 years of age, or in those with either hepatic or renal insufficiency. Tramadol should be avoided or used with caution in epileptics, or in individuals who are receiving seizure-threshold lowering drugs. Finally, tramadol has a low risk of abuse because it has only a weak opioid effect and its monoaminergic action could inhibit the development of dependence. The low abuse potential of tramadol has been demonstrated by postmarketing surveillance data.
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PMID:The tramadol option. 1131 Apr 78


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