摘要:

SummaryFosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. After absorption, phenytoin is cleaved (conversion half-life 8–15 min) from fosphenytoin. Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions (including standard intravenous solutions) and rapidly absorbed by the intramuscular route. Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus. Local toxicity (pain, burning, itching) is less by the intramuscular or intravenous route for fosphenytoin than for standard injectable sodium phenytoin. Systemic toxicity is similar with both preparations except that hypotension is less common and paresthesias are more common with fosphenytoin.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryRatios of phenytoin and carbamazepine doses to steady-state plasma concentrations of the drugs (apparent clearances) increase in pregnant women. Mean phenytoin clearance to urinary unconjugatedp-hydroxyphenytoin increased from 0.28 ± SD 0.18 to 0.74 ± SD 0.37 L/day in 13 pregnant women; mean clearance top-hydroxyphenytoin glucuronide increased proportionately less (15.25 ± SD 5.43 to 31.94 ± SD 16.30 L/day), the proportion of the metabolite that was conjugated falling from 98.4 ± SD 0.72% to 97.65 ± SD 0.67%. Mean clearances to urinary phenytoin and phenytoin-dihydrodiol did not increase. In 10 epileptic women, mean clearances of carbamazepine to urinary (a) carbamazepine-10,11-epoxide (1.66 ± SD 1.2 to 3.70 ± SD 2.09 L/day), (b) unconjugated carbamazepine- 10,11-trans-diol (33.93 ± SD 10.21 to 47.01 ± SD 19.58 L/day), (c) unconjugated carbamazepine-acridan (0.24 ± SD 0.12 to 0.47 ± SD 0.34 L/day), and (d) unconjugated 2-hydroxy-carbamazepine (0.08 ± SD 0.09 to 0.66 ± SD 1.14 L/day) all increased during pregnancy. Mean clearance to unconjugated 3-hydroxy-carbamazepine decreased (0.53 ± SD 0.25 to 0.18 ± SD 0.23 L/day). In contrast, mean clearances of carbamazepine to the glucuronides of its first stage metabolites (carbamazepine-diol, 2− and 3-hydroxy-carbamazepine and carbamazepine-acridain, respectively) did not increase in pregnancy. The conversion of carbamazepine to carbamazepine-epoxide increased proportionately more than the conversion of carbamazepine-epoxide to carbamazepine-diol. Pregnancy was thus associated with increased microsomal oxidations of phenytoin and carbamazepine, without proportionate increases in the subsequent hydrolysis of carbamazepine-10,11-epoxide and in theO-glucuronidations of the earlier stage metabolites.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryDepression frequently coexists with dementia, although in many cases the depression is not recognized clinically. Depression represents a major additional burden in dementia, not only for the patients but also for families, caregivers, and, economically, society as a whole. However, depression in patients with dementia does respond to treatment, and appropriate therapy can significantly improve the well-being of these patients. Depression in patients with dementia is currently treated with a variety of standard antidepressive agents (tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors), but none is free from significant side effects. Moreover, the use of these drugs is often complicated by a number of age-related factors or effects on the cholinergic neurotransmitter system. Consequently, an antidementia treatment with concomitant antidepressive properties and an acceptable benefit/risk ratio would represent an attractive therapeutic option. The pathogenesis of depression in patients with dementia is not well understood, but may be related to increased intracellular calcium ions in the CNS, the so-called “calcium hypothesis.” This hypothesis may explain why some calcium antagonists exert psychotropic effects, including putative antidepressant activity. Animal models and clinical data provide support for the use of calcium channel antagonists for the treatment of depression, with the potential for good tolerability. The latter aspect is especially important for elderly patients with dementia. Although antidepressive effects have been seen with a number of calcium channel antagonists, the dihydropyridine derivative nimodipine shows particular potential for clinical use, perhaps because nimodipine is one of the most lipophilic of these drugs and therefore achieves high concentrations in the CNS, and because of the unique biochemical properties of the dihydropyridine compounds compared with other L-type calcium channel blockers. Nimodipine also increases somatostatin levels in CSF, one of the cardinal biochemical deficits in Alzheimer's disease. Data obtained incidentally from the use of nimodipine in the treatment of elderly demented patients clearly demonstrate significant antidepressant activity by the drug in this patient group. Formal clinical evaluation is therefore recommended to establish more clearly the therapeutic benefits offered by nimodipine in patients who suffer from both dementia and depression.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryWe investigated the effects of apomorphine administration at two different doses (2–10 μg/kg, s.c.) in 35 migraineurs in headache-free period and in 20 age-matched healthy control subjects, with and without pretreatment with domperidone. Neither patients or controls complained of headache at either dose, whereas at the dose of 10 μg/kg migraineurs showed a statistically significant higher incidence of dopaminergic symptoms (nausea, vomiting, drowsiness, yawning, dizziness, sweating) than controls. Furthermore, symptoms due to postsynaptic dopamine receptors activation (i.e., nausea and vomiting) only appeared in migraineurs. No symptom, however, resembled those characterizing a spontaneous migraine attack. In conclusion, migraineurs show a lower threshold for dopamine receptor activation than normal subjects.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryThe purpose of this study was to investigate the clinical and electromyographic effect of turn/amplitude analysis (TAA)-guided botulinum toxin administration in patients with cervical dystonia. Involuntary electromyographic activity was recorded from both sternocleidomastoidei, both splenii capites, and both trapezii muscles of 13 torticollis patients, aged 34–73 years, before and after botulinum toxin A (Dysport) application. Dystonic muscles were selected for the injection if mean turns/s exceeded a level of 200. Four weeks after treatment with a mean dose of 223 μ/subject, clinical improvement was observed in 12 patients (92%) and only one patient reported no effect. Electromyographic improvement could be observed in 10 patients (77%). Both turns/s and the amplitude/turn decreased by 27% on the average after treatment. The electromyographic toxin effect showed a good correlation with the clinical toxin effect (r= 0.6). No dose dependency of the changes in turn/amplitude parameters could be observed. We found TAA a valuable modality for targeting and selecting dystonic muscles and for assessing the therapeutic benefit of the toxin.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryCimetidine and ranitine are histamine H2-receptor blockers widely used for the treatment of gastric hypersecretion and duodenal pathologies. They are known to induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of the drugs were selected. This syndrome was associated with a drop in plasma prolactin levels. The symptoms of this syndrome were greatly improved by restoration of treatment with the same drugs and reappeared when the treatment was again suspended. This syndrome was inhibited in 36 patients by administration of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing the blood-brain barrier, as compared with 10 control patients treated with placebo. These results suggest that the drop in prolactin levels occurring when cimetidine and ranitidine are suspended may contribute to the development of this syndrome. Also, the withdrawal of H2-receptor blockers could be included among the possible causes of some neurotic syndromes.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryL-Dopa is the most effective drug known for the treatment of Parkinson's disease. However, the large doses required to treat this neurodegenerative disorder can significantly affect tissue concentrations of sulfur amino acid metabolites due to peripheral and centralO-methylation. These effects include decreases in tissue concentrations of the biochemical methyl donorS-adenosylmethionine (SAM), increases in tissue concentrations of the methylation inhibitorS-adenosylhomocysteine (SAH), and increases in plasma concentrations of homocysteine, recently identified as an independent risk factor for vascular disease. In the present study, the ability of the catechol-O-methyltransferase inhibitor Ro 41–0960 to prevent L-Dopa-induced changes in SAM, SAH, and homocysteine concentrations was determined in rats. Rats were injected intraperitoneally with Ro 41–0960 or vehicle 30 min prior to an intraperitoneal injection of L-Dopa or vehicle. One hour after the second injection, the rats were killed and their brains, livers, spleens, kidneys, and plasma collected. SAM and SAH concentrations were then determined in discrete brain regions and peripheral tissues, and total homocysteine concentrations were determined in plasma. In the rats treated with only L-Dopa, decreased SAM concentrations and increased SAH concentrations were found in all brain regions and peripheral tissues measured, and increased homocysteine concentrations were found in plasma, consistent with previous reports. In rats pretreated with Ro 41–0960, however, these L-Dopa-induced effects on sulfur amino acid metabolite concentrations were attenuated or prevented entirely. It remains to be determined if this sparing effect of Ro 41–0960 on sulfur amino acid metabolites has clinical significance.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryTo determine if the combination of levodopa (LD) plus bromocriptine (Br) in the early stages of Parkinson's disease (PD) permits reduction of LD dosage and consequently results in fewer motor fluctuations and dyskinesias, a double-blind, multicenter prospective study in 50 PD patients who had responded favorably to LD while under treatment with that drug for ≤6 months was undertaken. Patients were randomized into two parallel groups (LD alone and LD plus Br). During the first placebo-controlled stage of the study lasting 8 months, association of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Br, there was a tendency toward smaller daily requirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 ± 240 vs. 725.6 ± 230 mg/day; p < 0.01) after 44 months of continuous treatment in the 40 patients still enrolled in the open-label stage. At that point in time, the mean dose of Br had been increased by 9.2 mg in the combined treatment group, and the mean dose of LD was 40.7% lower than in the group receiving LD alone. On subsequent evaluations, the number of patients with dyskinesias or describing wearing-off fluctuations severe enough to require changes in treatment was lower than in the group under combined therapy, the differences being significant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14.2%). Our results support early combined LD-Br therapy in PD, but no conclusions can be drawn as to whether this dopamine agonist exerts a preventive effect on the late side effects of LD or has another mechanism of action.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryWe report the cases of two patients with complaints of dysphagia following long-term neuroleptic therapy. Esophageal contrast radiography revealed that one patient suffered disruption of the normal swallowing activity of the pharyngoesophagus due to tardive dyskinesia. Her dysphagia disappeared following changes in her neuroleptic medications and the administration of clonazepam. The other patient demonstrated severe rabbit syndrome involving the glossopharynx. This 3-Hz rhythmic movement disorder resolved following injection of an anticholinergic agent. Thereafter, the addition of oral trihexyphenidyl to her medication regimen improved her dysphagia. It should be emphasized that the differential diagnosis of neuroleptic-associated dysphagia subtypes is important because therapeutic strategies differ depending on the subtype of this life-threatening illness.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SummaryRisperidone (Risperdal) is a recently released novel antipsychotic medication. It is different from the conventional neuroleptics, such as haloperidol, as it has both serotinergic and dopaminergic activity. It has a more tolerable side-effect profile compared with other antipsychotic medications. We review the literature regarding the side effects of risperidone use, describe a case of overdose with risperidone, and discuss the clinical sequelae and management of such an overdose.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID