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)

The distribution of cis-diamminedichloroplatinum (CDDP) was studied in 23 patients undergoing surgical resection of brain tumors metastatic from lung cancer. CDDP (100 mg/m2) was administered intravenously (i.v.) or intra-arterially (IA) at the time of surgery, and various fluids and tissues were sampled for measurement of drug concentration. Comparison of the two routes of administration disclosed that the plasma level was slightly lower after IA than after i.v. infusion, whereas there was no difference between the two routes in terms of drug diffusion into the brain tissue adjacent to the tumor. However, IA administration resulted in an intratumoral drug concentration twice as high as that achieved with i.v. infusion. The tumor:plasma and tumor:adjacent brain ratios of drug concentration after IA injection were also twice those measured after i.v. administration. The distribution pattern of CDDP is characteristic of water-soluble agents. All patients experienced tolerable nausea and vomiting. Creatinine clearance was moderately reduced in ten cases, but no serious renal toxicity was observed. Seizures occurred postoperatively in nine patients. Infrequent side effects were myelosuppression, ototoxicity, and postoperative intracranial bleeding. All adverse effects disappeared with conservative treatment or no intervention.
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PMID:cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. I. Distribution within the central nervous system after intravenous and intracarotid infusion. 841 Jan 44

A 78-year-old woman was admitted to our hospital because of disorientation and fever on January 21, 1992. Two days before admission she experienced vomiting, anorexia and general malaise. Laboratory examinations on admission disclosed a hemoglobin level of 11.1 g/dl and a platelet count of 8,000/microliters. The peripheral blood smear revealed anisocytosis with numerous schistocytes and poikilocytes. Polychromatophilic and nucleated red blood cells were also seen, and the reticulocyte count was 38/1000. Her serum lactate dehydrogenase (LDH) value was 2,977 WU and the total serum bilirubin level was 3.5 mg/dl with 2.7 mg/dl indirect reacting fraction. Serum creatinine was 4.7 mg/dl. Her consciousness became semicomatose after a systemic seizure which lasted approximately 15 seconds and her hemoglobin level decreased to 8.5 g/dl on hospital day 2. Therefore, we diagnosed her as having thrombotic thrombocytopenic purpura (TTP) because of the presence of all 5 features, that is, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic abnormalities, renal dysfunction and fever. A plasmapheresis with fresh frozen plasma (FFP) replacement was begun on that day. She was also treated with anti-platelet agents, 80 mg/day aspirin, and 300 mg/day dipyridamole. Moreover, packed red blood cells (PRC) were infused. While also receiving diphenylhydantoin and phenobarbital to prevent convulsions, status epilepticus developed on day 3. Because of inhibited spontaneous respiration which was an adverse effect derived from diazepam and sodium thiamylal administered intravenously to treat the status epilepticus, an artificial respiration was initiated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An elderly case of thrombotic thrombocytopenic purpura]. 848 87

A 44-year-old Spanish woman travelled in Kenya without doing correct malarial prophylaxis. Upon her return to Spain, she suffered from Plasmodium falciparum malaria. She was initially treated with chloroquine for three days, but her state worsened and she was admitted to our intensive care unit. On admission, parasitaemia was 22%. She had hyperpyrexia, obtundation, hypotension, tachycardia, tachypnoea, jaundice, digestive haemorrhage, petechiae in her soles, oliguria with elevation of serum uraemia and creatinine, anaemia, thrombocytopaenia, hypoproteinaemia, hyponatraemia, hypocalcaemia, metabolic acidosis and parameters of disseminated intravascular coagulation. She was given quinine, sulfadoxine-pyrimethamine and clindamycin. An exchange transfusion was performed, during which an acute pulmonary oedema appeared, initially with high pulmonary artery wedge pressure. She required mechanical ventilation for 16 days and haemodialysis for 11 days. She remained in coma and had seizures which required diazepam, phenitoin and thiopentone. She received a total amount of 22 units of packed erythrocytes, 55 of platelets and 15 of plasma. After the first week, she had nosocomial infection due to Escherichia coli, Staphylococcus and Pseudomonas aeruginosa and was treated with the corresponding antibiotics. She cured completely. This case report gives us the possibility of discussing on frequent problems in the prevention and treatment of malaria, and on the treatment of severe, life-threatening malaria in the setting of the intensive care unit.
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PMID:[Multiple organ failure in Plasmodium falciparum malaria]. 853 25

Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body weight/d. Clinical signs included hind limb weakness, ataxia, and disorientation. Renal insufficiency, diagnosed by determination of endogenous creatinine clearance, was believed to be responsible for the development of bromide toxicosis in this dog. Diuresis with physiologic saline solution and discontinuation of bromide and phenobarbital treatment resulted in rapid resolution of abnormal neurologic signs; however, serum bromide concentrations decreased dramatically during diuresis and seizures recurred. Although saline diuresis has been recommended for the treatment of bromide intoxication in human beings, more conservative measures, such as discontinuation of bromide and short-term fluid administration, may be more appropriate for epileptic dogs.
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PMID:Bromide toxicosis secondary to renal insufficiency in an epileptic dog. 856 78

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.
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PMID:Gabapentin: pharmacokinetics, efficacy, and safety. 868 9

The amino acid antiepileptic drug (AED) gabapentin (GBP) is indicated for adjunctive use in the treatment of partial seizures with or without becoming secondarily generalized in individuals older than 12 years. GBP was about as potent as phenytoin in the maximal electroshock test, but had a different profile of efficacy than standard antiepileptics in a range of animal models. Possible mechanisms of action include biochemical effects enhancing the ratio of gamma-aminobutyric acid (GABA) to glutamate, ion-channel actions (direct or indirect), and/ or enhancement of nonsynaptic GABA release. The anticonvulsant effect appears to depend on concentration of gabapentin in neurons, presumably by the L-system amino acid transporter that has been implicated in absorption from the gut. Data from studies for U.S. Food and Drug Administration (FDA) approval suggested a direct relationship of clinical response to dose and efficacy did not plateau at the doses used. The maximally effective dose, relationship of efficacy to blood level, and maximum tolerable dose are not yet known conclusively. Lack of significant binding to plasma proteins and lack of liver metabolism contribute to the absence of known limiting drug-drug interactions, particularly with other AEDs. Excretion intact in the urine affords dose adjustment on the basis of creatinine clearance. A half-life of approximately 7 h necessitates multiple doses daily for many individuals. The medication is well tolerated, in general. Side effects tend to be mild to moderate in intensity, most frequently affect the central nervous system, and resolve with time in many individuals. GBP has been prescribed for approximately 70,000 individuals worldwide without untoward incidence of severe systemic toxicity to date. Safety data continue to accumulate. GBP has been labeled category C on the basis of effects on rodent fetuses. Experience with use in pregnant women is limited and human teratogenic effects have not been reported. Data from ongoing monotherapy trials will help to clarify the range of clinical utility of gabapentin.
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PMID:Gabapentin. 878 16

Patients with epilepsy on long term antiepileptic drug (AED) therapy deserve special consideration not only concerning seizure control but also the effect on anaesthetic metabolism and hepatorenal functions. In the present study, we examined the effects of sevoflurane anaesthesia on plasma inorganic fluoride (F-) level and hepatorenal function in patients with and without AED therapy. Twenty-two patients (12 with AEDs = AED group, and ten without AEDs = control group = C group), ASA I, who were free of hepatorenal disease, received approximately 2-3 h sevoflurane anaesthesia. Plasma F- analysis was performed at the stages of: 1) induction of anaesthesia, 2) conclusion of anaesthesia, 3) 15 h after the conclusion of anaesthesia, using an ion-selective electrode calibrated with a standard solution of sodium fluoride. Pre- and postoperative hepatic (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin) and renal (blood urea nitrogen, creatinine) function was tested. There were no significant differences between the two groups in the average age (AED group = 9.4 and control group = 10.1 y.o.), body weight, duration of anesthesia, and MAC hours (2.6 and 2.4). The mean peak F- levels were 15.5 and 13.6 microM, in AED and C groups (not significant), respectively. No patient exhibited F- values greater than 50 microM, the hypothetical nephrotoxic threshold. The patients showed no abnormal values either in hepatic or renal function tests postoperatively. These results suggest approximately 2-3 h sevoflurane anaesthesia to be safe in patients taking AEDs.
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PMID:Clinical characteristics and biotransformation of sevoflurane in paediatric patients during antiepileptic drug therapy. 888 Aug 18

Data obtained from 23 critically ill patients treated with intravenous ciprofloxacin in two clinical trials were used to validate prospectively a previously developed maximum a posteriori (MAP)-Bayesian estimator and optimal plasma-sampling strategy (OSS). Dosages ranged from 200 mg every 12 hours to 400 mg every 8 hours. Each patient had 8-16 samples taken, either as large gold standard sampling sets or as a mix of gold standard sets and OSSs. The MAP-Bayesian estimator used a two-compartment model and identified apparent volumes of distribution of the central and peripheral compartments, distributional clearance, and the slope and intercept of the relationship between creatinine clearance and total body clearance. Fit parameters were used to derive the apparent volume of distribution at steady state and the 24-hour area under the curve. All parameters derived from the OSS using the MAP-Bayesian estimates matched up almost identically to those obtained from modeling the gold standard sets. There was no systematic bias, and good precision was seen among all the parameters. These data demonstrate the usefulness and validity of the current OSS and MAP-Bayesian estimator, and provide further evidence of the utility of optimal sampling theory.
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PMID:Prospective validation of an optimal sparse plasma-sampling strategy for estimating ciprofloxacin pharmacokinetics. 888 90

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.
Seizure 1996 Sep
PMID:Vigabatrin dosing during haemodialysis. 890 28

Thiazides and amiloride are the most often suggested treatment for nephrogenic diabetic insipidus. We found this ineffectual in a patient with acute problems and reviewed the literature to see if there were other more efficient approaches. A 47-year-old woman on lithium had polyuria. When inadvertently fasted for 48 h she became confused, had a seizure, and her sodium was 170 mmol/L. Urinary output was 24 L/day. Large volumes of intravenous fluids were given but sodium remained > 170 mmol/L. Treatment with DDAVP, thiazides, and amiloride did not decrease urinary output. Indomethacin 150 mg was started and urine volume immediately fell to one-half. However, because of persistent high urine output the patient was then fluid depleted, with further reduction to normal in urine volume, and Na decreased to 140 mmol/L. Creatinine rose from 135 mumol/L to 173 mumol/L, but decreased to 152 mumol/L when indomethacin was decreased to 75 mg q.d.; urinary output remained stable around 2 L/day. The literature described 22 patients with nephrogenic diabetes insipidus (16 congenital, 6 lithium) treated with nonsteroidal anti-inflammatory drugs. Urine flow was reduced to 1/3, within hours. Rarely, mild renal failure ensued, improving in all but one case when nonsteroidal anti-inflammatory drugs were reduced. Indomethacin (and controlled volume reduction if continued high urine output), while observing renal function, appears the emergency treatment of choice for serious complications of nephrogenic diabetes insipidus.
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PMID:Emergency treatment of lithium-induced diabetes insipidus with nonsteroidal anti-inflammatory drugs. 904 66


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