Serum Levels Of Anticonvulsants Research Articles

Interacciones medicamentosas de los anticonvulsivantes de primera línea con antipsicóticos y/o antidepresivos

ObjectiveIdentify drug interactions of old antiepileptic drugs with antidepressants and antipsychotics and its impact on the patient with epilepsy at the Hospital de San José in outpatient appointment from June 1st, 2015 to the april 30th, 2016. Material and methodsA descriptive study was conducted to identify drugs interactions in patients diagnosed with epilepsy. The study involved patients over 18 years old with a diagnosis of epilepsy according to the International League Against Epilepsy criteria in therapy with first line antiepileptic drugs associated with antipsychotic drugs or/and antidepressants, excluded pregnant women, patients with hepatic and renal impairment. The statistic analysis of qualitative variables was performed using absolute and relative frequencies. Quantitative variables were analysed using medians and interquartile ranges. ResultsWe included 26 patients with a median age of 49 years (IQR: 33-57), 14 were women (53.8%). The most relevant conditions on past medical history were perinatal hypoxia and brain trauma, both diagnosed on 5 patients (19.2%). The most frequently anticonvulsant monotherapy used was carbamazepine, which was prescribed on 8 patients (30.8%). Only two patients receiving carbamazepine presented leucopenia. None of the patients presented elevated liver enzymes. Anticonvulsant serum levels in most therapies were within the therapeutic range. Discussion and conclusionsWe described multiple combinations of anticonvulsants with antipsychotics and/or antidepressants. No liver toxicity or serious hematologic abnormalities that could suggest a change on the therapy was documented. Furthermore, most anticonvulsants serum concentration remained within the therapeutic range.

Correlation between Serum Level of Antiepileptic Drugs and their Side Effects

The aim of the study is to investigate the relation between serum levels of anticonvulsants and their side effects. This is a prospective cross sectional hospital based study conducted at Al Shaab Teaching Hospital. 120 patients were included in the study. The AEDs used were phenytoin, phenobarbitone, carbamazibine, and sodium valproate. The results showed that the side effects among the studied group were not uncommon. There was no relationship between serum levels of AEDs and their side effects.

Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors.

Procarbazine usage in brain tumors has a high incidence of hypersensitivity reactions compared with its use in other malignancies. Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital. Patients with primary brain tumors would have a preferential exposure to anticonvulsants compared to patients with other malignancies. To determine whether anticonvulsant exposure is associated with procarbazine hypersensitivity reactions in patients with primary brain tumors. This retrospective cohort study included 83 patients with primary brain tumors who were treated with procarbazine between 1981 and 1996 at a university hospital-based regional oncology center. Data were extracted by chart review. The data collected included age, sex, race, tumor type, smoking, alcohol usage, and all concomitant medications, as well as creatinine, aspartate aminotransferase, total bilirubin, and anticonvulsant serum levels. Anticonvulsant exposure was determined by the presence of detectable serum levels. Cases of procarbazine hypersensitivity reactions were identified through a review of progress notes. There were 20 patients with procarbazine hypersensitivity reactions. A significant association between the exposure to anticonvulsants and the development of procarbazine hypersensitivity reactions was found (p = 0.05). In addition, there was a significant dose-response association between the development of procarbazine hypersensitivity and the presence of therapeutic anticonvulsant serum levels (p = 0.03). Concomitant exposure to anticonvulsants is associated with procarbazine hypersensitivity reactions, possibly though a reactive intermediate generated by CYP3A isoform induction. All patients in this cohort received enzyme-inducing anticonvulsants. New anticonvulsants devoid of this property are available. These data support trials that use these newer agents for the prophylaxis of seizures in patients with brain tumors who are to receive procarbazine.

Changes in serum anticonvulsant levels with febrile illness in children with epilepsy.

Changes in anticonvulsant serum levels during intercurrent illness may cause toxicity or decreased seizure control in children with epilepsy. We studied prospectively the effect of intercurrent illness and its treatment in 111 children being treated with AC monotherapy. Free fraction and total serum AC levels were determined when the child was well, on the fifth day of any illness with fever and one month after recovery. There were 55 episodes of febrile illness in 39 children during the study period. Twelve illnesses were associated with significant increases or decreases in serum AC levels; 7 children became clinically toxic; 1 child had increased seizures during illness. The mechanisms of AC level changes appeared to include interaction with antibiotics, with antipyretics or with viral illness. Amoxycillin and acetaminophen did not appear to interact with the AC's used. Physicians caring for children with epilepsy should be aware of the frequency and complexity of potential interactions between intercurrent febrile illness and anticonvulsant medication.

Cardiopulmonary arrest following intravenous phenytoin loading

Two patients, aged 44 and 68 years, presented with generalized seizures either witnessed or highly suspected. Both patients had laboratory-proven subtherapeutic anticonvulsant serum levels. The patients differed with regard to risk; one patient had existing cardiopulmonary disease, and the other was free of such risk factors except liver disease. An apparently appropriate dose of intravenous phenytoin was initiated in each case, and the patients were monitored appropriately and given supplemental oxygen. Bradycardia, hypotension, respiratory distress, and, ultimately, cardiopulmonary arrest occurred in both. The criteria proposed by Earnest et al. should be implemented for each seizure case that requires a decision on the urgent need for therapeutic anticonvulsant levels, whether by mechanical infusion, manual intravenous push, or oral loading. The mechanical infusion is the easiest method to standardize and monitor. The manual intravenous push has a greater possibility of inadvertent overdosage during some small time frame, as well as more local symptoms by some reports. Record et al. have recommended oral loading in selected patients. Careful consideration must be made of the choice of environment in which intravenous loading is done (e.g., emergency department, intensive care unit), as dictated by patient parameters, nursing staff levels, and planned disposition. The crucial factors contributing to the deterioration of both patients in the two cases presented were the concentration of phenytoin manually infused and the possibility that their high-risk status made them poor candidates for manual intravenous phenytoin. Dose and a hypersensitivity reaction were doubtful factors in these cases.

Generalized Seizure Triggering Threshold and Serum Phenobarbital Levels During Pregnancy in Rats

In experiments using pregnant rats, the following results were noted: (a) Of the amygdaloid kindled rats, the generalized seizure triggering threshold of the pregnant group was significantly higher than that of the nonpregnant group. (b) Of the rats taking oral phenobarbital, 4 mg/kg once a day, there was no significant difference of serum levels between the pregnant group and the nonpregnant group. (c) Of the amygdaloid kindled rats taking oral phenobarbital, 4 mg/kg once a day, the generalized seizure triggering threshold of the pregnant group was significantly higher than that of the nonpregnant group. It may be suggested that, when the drug dose remains the same, the rise in threshold by gestational physiological changes antagonizes the fall in threshold by decreased serum levels of anticonvulsants because of increasing distribution volume due to increasing body weight during pregnancy.

Anticonvulsant serum levels are useful only if the physician appropriately uses them: an assessment of the impact of providing serum level data to physicians.

The ability to measure serum levels of anticonvulsants has been a significant advance in the treatment of epilepsy. This technique enables practitioners to monitor a patient's plasma concentration, to detect potential toxicity, and to assess compliance with the prescribed regimen. A retrospective study of 164 adults with epilepsy was conducted to evaluate how serum anticonvulsant determinations were used by physicians in their treatment of epilepsy. Results indicate that the availability of test results did not improve the degree of seizure control, nor did it diminish patient reports of toxicity. In 17% of therapeutic decisions, prescribers did not appear to use the blood levels appropriately in their therapeutic decision-making process. When physicians did appropriately utilize information from serum levels, the degree of seizure control improved significantly compared with when the prescribers did not use this information. The cost of determining serum levels of anticonvulsants is justified only if the information is appropriately utilized.

Anticonvulsant serum levels: relationship to impairments of cognitive functioning.

Twenty-eight patients with epilepsy were seen on two occasions at an interval of three months. On one session anticonvulsant serum levels were high and on the other session the serum levels were lower. On each of the two sessions patients performed a series of psychological tests and had a blood sample taken for the analysis of anticonvulsant serum concentrations. Seizure frequency in the previous three months was documented and several patients had an EEG recording made. Deficits in psychological test performance were found at high serum concentrations. Furthermore, lower serum level concentrations did not appear to be accompanied by worsened seizure control.

Anticonvulsant drugs and cognitive functions.

Thirty-five patients with epilepsy were seen before and 3 and 6 months following changes in their anticonvulsant regimes. Patients either underwent a reduction in the number of different drugs prescribed (n = 20) or had at least one drug changed to carbamazepine (n = 15). A third group of patients was seen at the same time intervals but remained on stable anticonvulsant therapy (n = 10). On each assessment session patients performed a series of specially designed tests of cognitive and motor functions, completed rating scales of mood, had a blood sample taken for the analysis of anticonvulsant serum levels, and had their seizure frequency for the previous 3 months documented. In addition, 24 patients had a routine EEG recording made. The overall results obtained suggested that a reduction in polypharmacy and the use of carbamazepine both had beneficial effects on cognitive functioning and mood.

Iatrogenic Behavioral and Psychiatric Symptoms in Children With Partial Complex Seizures

Reports are presented of two children with partial complex seizures (PCS) who had a variety of behavioral and psychiatric symptoms that were related to toxic serum levels of anticonvulsants. Anticonvulsant toxicity should be considered in the differential diagnosis of psychiatric symptoms in all children with convulsive disorders. The traditional view that the psychomotor spells have behavioral and psychiatric components increases the complexity of the differential diagnosis. PCS in children present differences in symptomatology and more difficulties in diagnosis and treatment compared with adults.

PREVENTION OF INTRAVENTRICULAR HAEMORRHAGE IN PRETERM INFANTS BY PHENOBARBITONE: A Controlled Trial

Sixty infants with birth-weights less than 1500 g and who were less than 6 h old were randomly assigned to a group given phenobarbitone or a control group. Intravenous phenobarbitone was given in doses sufficient to achieve anticonvulsant serum levels within 12-18 h. Maintenance therapy was continued for one week. Periventricular/intraventricular haemorrhage (IVH) occurred in 133% (4/30) of the phenobarbitone group and in 46.7% (14/30) of the control group. The occurrence of risk factors related to IVH was similar in the two groups. Phenobarbitone may reduce the incidence of IVH in small preterm infants.

Relation of prophylactic medication to the occurrence of early seizures following craniocerebral trauma.

✓ In a series of 1614 cases of combat head injury incurred in Vietnam between 1967 and 1970, 70% received prophylatic anticonvulsant medication (diphenylhydantoin, 300 to 400 mg/day); 36 developed fits in the first week following injury. The prophylactic regimen had no recognizable effect. Therapeutic serum levels of anticonvulsants are not achieved for 2 or 3 weeks. Usefulness of dexamethasone in controlling brain swelling may be seriously impaired by diphenylhydantoin. Thus prophylaxis against early posttraumatic fits may not be practical or desirable.