Biomedical subjects

J L Herranz

Publications and source records attributed to J L Herranz.

At least 19 recordsLinked to original sources

PubMed2006

[Pharmacogenetics, pharmacogenomics and individualised antiepileptic therapy].

AIMS: Despite the large number of antiepileptic drugs (AED) currently on the market, in 20-30% of patients it is still not possible to achieve a total control of the seizures or to prevent the appearance of idiosyncratic side effects. DEVELOPMENT: In this study the pharmacokinetic and pharmacodynamic factors involved in pharmacoresistance in epilepsies are analysed, with special attention given to the polymorphisms of metabolising enzymes or their inducers, particularly the hepatic cytochrome CYP, the over-expression of membrane-transporting proteins -P-glycoprotein (PGP), MRP- and polymorphisms in the ion channels. Idiosyncratic effects are produced due to an imbalance between the production of toxic metabolites and the individual capacity to detoxify them. Pharmacogenetics and pharmacogenomics can identify certain personal, biochemical, enzymatic and genetic characteristics that are of use in selecting the most effective AED with the lowest risk of idiosyncratic effects for each person. CONCLUSIONS: Although new AED that can help reduce the number of medication resistant patients must be introduced, at the same other therapeutic strategies have to be developed with the aid of pharmacogenomics; more specifically there is a need for AED that are not transported by PGP o MRP, or substances that antagonise those membrane transporters and make it possible for the AED to reach the site where they are to act. Furthermore, the detoxification capacity of each individual must be known in order to be able to minimise the risk of idiosyncratic side effects.

Anticonvulsants↗

PubMed2002

[Characteristics and indications of oxcarbazepine].

OBJECTIVE: To review the major studies published concerning the pharmacokinetic characteristics, mechanism of action, clinical efficacy and adverse effects of oxcarbazepine (OXC). DEVELOPMENT: OXC is a ketoderivative of carbamazepine (CBZ), with a similar mechanism of action, possibly widening the voltage dependent potassium channels. Its pharmacokinetic characteristics are much better than those CBZ but the frequency and intensity of interactions is much less. In several double blind trials, using the drug in monotherapy in previously untreated patients, similar efficacy was found after OXC, phenytoin, valproate and CBZ but the fewest adverse effects were seen after OXC. CONCLUSIONS: OXC is an antiepileptic drug with better pharmacokinetic properties than CBZ and similar clinical efficacy, but better tolerated, so it may therefore be expected to replace this classical antiepileptic drug for use in monotherapy and polytherapy of both children and adults in all types of partial seizures.

Animals↗

PubMed2002

[Characteristics and indications of levetiracetam].

OBJECTIVE: To describe the data contained in the most important studies published on the pharmacokinetic and pharmacodynamic properties of levetiracetam, and also the main clinical trials carried out using this new antiepileptic drug. DEVELOPMENT: Derived from piracetam, but with very different properties, levetiracetam is ineffective in the usual models of seizures induced in experimental animals, although it acts in models of prolonged activation, audiogenous seizures and absences and has a novel mode of action. It has pharmacokinetic properties which are nearer to that of the ideal anti epileptic drug. In clinical trials done in adults with partial epilepsies use of 1,000 to 4,000 mg of levetiracetam was significantly more effective than a placebo, and the drug was very well tolerated. CONCLUSIONS: Levetiracetam is the newest antiepileptic drug to appear on the market. Its pharmacodynamic and pharmacokinetic characteristics are excellent. It has currently been approved for use in the polytherapy of patients with partial seizures aged over 16 years. Several studies indicate that its therapeutic spectrum is probably wider, particularly in generalized seizures such as the myoclonias, absences and seizures induced by light stimulation. Thus the indications for levetiracetam may become clear over the next few years.

Animals↗

PubMed2000

[Television and children: is television responsible for all the evils attributed to it?].

OBJECTIVE: The purpose of this study was to analyze children's television viewing habits and their parents attitudes towards such viewing. DESIGN: Cross-sectional descriptive study. SETTING: Primary care. PARTICIPANTS: A survey was undertaken with 317 three to fourteen year old children and their parents as part of the primary care check-up program for healthy children. MEASUREMENTS AND MAIN RESULTS: Time devoted to television viewing was 106 +/- 50 minutes on weekdays and 141 +/- 80 minutes weekends. Despite this, 49.2% of parents thought their children saw little television, especially those with children under six (57.6%). Children of parents in highly qualified positions and of parents in the uppermost socioeconomic group saw television the least, on non-working days (70 +/- 61 minutes and 144 +/- 78 minutes respectively, p < or = 0.0001). Some 71.9% of children watched television alone and 34% did so at meal-times. Altogether 48.3% of parents were unaware as to what their children watched and some 61.5% encouraged television viewing, above all those having children of under six (76%). The youngest children preferred to watch cartoons which were generally of a violent nature. For those aged from 11 to 14, 19.5% chose as their favorite programs those having a high level of violence. CONCLUSION: Television habits are an educational problem for parents, an important shake-up in their attitudes being called for, in which pediatricians should be involved in developing health programs aimed at proper use of the television.

Adolescent↗

PubMed2000

Cryptogenic gelastic epilepsy of frontal lobe origin: a paediatric case report.

Gelastic (laughing) seizures are an uncommon seizure type which in most cases has an organic cerebral pathology and specifically a hypothalamic hamartoma. The interictal EEG frequently shows focal activity. This report describes a 3 1/2-year-old boy who presented with episodes of unmotivated laughter associated with other epileptic symptomatology before the age of 3 years. Prolonged ambulatory EEG monitoring recorded electroclinical seizures starting in the right frontal area and spreading to the adjacent frontotemporal region. Neurological examination and brain magnetic resonance imaging were normal. Vigabatrin resulted in immediate remission of the seizures and normalization of the EEG.

Anticonvulsants↗

PubMed2000

[Current data on gabapentin].

OBJECTIVE: To review the current data on gabapentin (GBP) with regard to its mechanism of action, pharmacokinetic characteristics, clinical efficacy, tolerance and mode of administration. DEVELOPMENT: GBP has a multiple mechanism of action which justifies its use in many clinical conditions besides epilepsy. These include neuropathic pain, psychiatric disorders, disorders of movement, and migraine. Its pharmacokinetic characteristics are nearly those of an ideal drug, with no interactions. Regarding clinical efficacy, there is much evidence of this in polytherapy and in monotherapy in adults and children with partial crises, with rare adverse effects and the exceptional possibility to establish the total dose of GBP in only a few days. CONCLUSIONS: GBP is an effective drug in patients of all ages with partial crises. Because of its excellent tolerance and decreasing dose-dependent kinetics, conditioned by less absorption of the drug, we recommend the administration of GBP at doses higher than those normally used. Thus we suggest a dose of 900 to 2,400 mg/day in patients with a new diagnosis, of 1,800 to 3,600 mg/day as a second therapeutic alternative and even 2,400 to 4,800 mg/day when other antiepileptic drugs have failed to be of use.

Acetates↗

PubMed2000

[Current data on topiramate].

OBJECTIVES: To review current knowledge regarding the mechanisms of action, pharmacokinetics, clinical efficacy and the tolerance of topirimate (TPM) and describe the Spanish experience of the use of this drug in 224 patients of all ages. DEVELOPMENT: TPM is a new drug which affects practically all the mechanisms involved in the production of epileptic seizures, which means that it is a broad-spectrum antiepileptic drug. After reviewing the mechanisms of action and pharmacokinetic characteristics of TPM, we consider the efficacy of the drug in 224 patients of all ages with all types of epileptic seizures. CONCLUSIONS: In patients of all ages with uncontrolled epileptic seizures treated with TPM, the frequency of their seizures was reduced by over 50% in 78% of the patients and the seizures were abolished in 25% of the total cases. The drug was generally well tolerated. Side-effects leading to suspension of the drug occurred in only 5% of the cases. TPM is an effective drug which is well tolerated in patients of all ages and with all kinds of epilepsy.

Anticonvulsants↗

PubMed2000

[Current data on tiagabine].

OBJECTIVE: To review current data regarding the mode of action, pharmacokinetics, clinical efficacy and tolerance of tiagabine (TGB). DEVELOPMENT: TGB is a drug which boosts gabergic inhibition by blocking the re-uptake of synaptic GABA by the glia and neurones. This specific mode of action leads to an antiepileptic effect in patients of all ages with partial seizures. The efficacy of TGB is complemented by good tolerance, especially when it is introduced slowly, over a period of eight weeks. This form of administration is also used with other new antiepileptic drugs, such as lamotrigine and topiramate. We consider the data regarding efficacy and tolerance found in the clinical trials and studies reported in the literature. CONCLUSIONS: TGB is an effective, well-tolerated drug when used in patients with difficult-to-control partial crises. However, it should also be used in patients with less difficult-to-control seizures and in previously untreated patients so as to properly define its efficacy and tolerance.

Adolescent↗

PubMed2000

[Economic aspects of epilepsy].

INTRODUCTION: The economic magnitude of epilepsy is determined by its effect on the employment status of the patients, the cost of drug treatment for them and the healthcare system and the repercussion worldwide. DEVELOPMENT: Studies of the cost of the disease show that it has economic importance due to the sum of the direct and indirect costs caused by it. In the case of epilepsy, the results of studies in various countries led to the creation of a Commission on Economic Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in Spain may explain the lack of publications on this subject in our country. The percentage of the total cost due to antiepileptic drugs is considerable and will probably increase in the future. The pharmaco-economic evaluation made by cost-benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize costs should serve to use healthcare resources in the most effective manner and justify the rational use of the new antiepileptic drugs. CONCLUSIONS: The economic impact of epilepsy is added to the repercussion of the disease itself on the patient and his family. The different distribution of costs in children and adults with epilepsy suggest the need for intervention at an early age to try to reduce the long term economic and personal repercussions. The pharmaco-economic evaluation of the new antiepileptic drugs will make it clear whether their considerable cost is worth paying for their greater effectivity.

Adult↗

PubMed1999

Lamotrigine serum concentration-to-dose ratio: influence of age and concomitant antiepileptic drugs and dosage implications.

Using bivariate and multivariate methods, we retrospectively analyzed the influence of patient age and the use of concomitant antiepileptic drugs (AEDs) on the lamotrigine (LTG) concentration-to-dose (C/D) ratio in samples from 164 patients (68 children, 96 adults) with epilepsy receiving LTG alone (n = 28) or in combination with various antiepileptic drugs (n = 136). The LTG C/D ratio increased with age in children receiving LTG alone (r = 0.60, p < 0.01), but decreased with age in adults receiving LTG and inducers (r = -0.42, p < 0.001). In patients receiving LTG and inducers, the ratio was statistically lower in those younger than 9 years of age (0.23 +/- 0.08) and older than 30 years of age (0.32 +/- 0.15) than it was in those between 9 and 30 years of age (0.44 +/- 0.15). The mean LTG C/D ratio was 0.37 +/- 0.15 in patients receiving LTG and inducers (n = 92), 0.84 +/- 0.41 in patients receiving LTG alone (n = 28), 1.09 +/- 0.44 in those receiving LTG with VPA plus inducers (n = 17), and 3.41 +/- 1.18 in those receiving LTG and VPA (n = 27). Differences in the LTG C/D ratio between treatment groups were similar in children and in adults. We reached the following conclusions: The LTG C/D ratio increased with age in children but may decrease with age in adults receiving concomitant enzyme-inducing AEDs; the LTG C/D ratio was 10 times lower in patients receiving LTG and inducers than in those receiving LTG and VPA (in both children and adults), and this difference was higher than the four-fold difference described for LTG half-life and the two-fold differences currently used in LTG dosage.

Adolescent↗

PubMed1999

[Epileptic signs of metabolic origin].

INTRODUCTION: It is very difficult to identify metabolic causes of epileptic crises. This is partly because metabolic disorders are not fully understood and partly because the complementary tests required for their identification can be undertaken only in a few laboratories. DEVELOPMENT: We describe the characteristics of the metabolic disorders which may most frequently lead to epileptic crises occurring during the neonatal period, the first year of life, between the ages of one and six years and between six and fifteen years of age. We also emphasize the findings which may help in orientation towards diagnosis of these metabolic disorders, and the complementary tests required for confirmation.

Child↗

PubMed1998

Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey.

A collaborative survey was performed to compare prescribing strategies for the treatment of epilepsy in Mediterranean countries, based on analysis of 500 questionnaires compiled by physicians in 14 different countries. For partial seizures, carbamazepine was the drug of choice in most countries, whereas the second choice of drug differed widely. For primarily generalized tonic-clonic seizures, valproic acid was usually preferred, but other drugs used widely in some countries included phenobarbital, phenytoin and carbamazepine. Lamotrigine was the most popular second-line drug for primarily generalized tonic-clonic seizures in the European countries. In patients where the initial drug failed, switching to an alternative monotherapy was usually the preferred strategy, but advocates of early use of combination therapy exceeded 30% in the respondents of seven countries. Most respondents, in all countries except Turkey, did not prescribe drugs to prevent recurrence of febrile seizures; however, intermittent prophylaxis with a benzodiazepine was advocated by a considerable number of physicians, and continuous prophylaxis was prescribed by a significant minority of respondents in France, Syria and Tunisia. New drugs were rarely used as first-line treatment due to high cost and inadequate experience. Overall, this survey indicates that there is a wide variability in therapeutic practices between and within countries. This information may be useful for the implementation of national educational activities and for the design of pragmatic trials aimed at comparing different therapeutic strategies.

Adult↗

PubMed1998

Seizure recurrence and risk factors after withdrawal of chronic antiepileptic therapy in children.

The aim of this study was to identify the risk factors for seizure recurrence after withdrawal of chronic antiepileptic therapy in 226 children: 136 with partial epilepsies and 90 with generalized epilepsies. The influence on prognosis of the different variables was assessed retrospectively with univariate and multivariate analysis. With a mean observation period of 5.85+/-3.87 years, seizure recurrence occurred in 24.3% of all patients with partial and generalized epilepsies. In children with partial epilepsies, the following factors were found to significantly increase relapse risk after treatment withdrawal: neurological abnormalities; interval between seizures less than 1 month at onset of illness; the use of VPA in treating seizures; start of withdrawal after 6 years of age; frontal paroxysmal activity; and abnormal EEG before drug withdrawal. In children with generalized epilepsies the risk factors were found to be: abnormal neonatal period; first seizure after 10 years of age; mean duration of seizures greater than 1 minute; poor school progress and generalized spike-waves in EEG. The factors associated with the risk of recurrence in children with generalized epilepsy appear to differ from to those related to partial epilepsies, in which seizure treatment with VPA was associated with an increased recurrence risk after the withdrawal of antiepileptic drugs.

Adolescent↗

PubMed1998

[Diagnostic focus on the child with myoclonic seizures in isolation or associated with other types of seizures].

Myoclonus may be observed in children with mild or severe epileptic syndromes. Both types are seen at characteristic ages, together with other factors: aetiology, family history, hereditary pattern, effect on psychomotor development and EEG-EMG findings. In children with progressive or degenerative encephalopathies and myoclonus, better known as progressive myoclonic epilepsy, there are also specific clinical data, together with biological and genetic markers which permit identification. The most specific clinical characteristics of each of these clinical pictures are described, as are the complementary tests which permit confirmation of these diagnoses.

Adolescent↗

PubMed1998

[Tiagabine: recent findings and recommendations for dosage].

INTRODUCTION: Tiagabine causes GABA to remain in the synapses longer since it inhibits the protein GAT-1, which normally transports GABA for uptake by the glia and neurones. DEVELOPMENT: With its advantageous pharmacokinetics, it is particularly effective in patients with complex partial crises, and leads to complete control in 53% of new patients treated with tiagabine alone. Side effects are infrequent, especially when treatment with the drug is started gradually and increased weekly. The lowest effective dose has been found to be 15 mg/day. The usual maintenance dose is between 15 and 30 mg/day taken divided into 2 or 3 doses per day.

Dose-Response Relationship, Drug↗

PubMed1998

[Suggestions regarding new classification of epileptic seizures].

INTRODUCTION: A modification of the current classification of epilepsy is proposed taking the clinical and neurophysiological knowledge of recent years into account. DEVELOPMENT: In the first group (partial seizures) those of unknown type are added. In the second group (generalized seizures) typical and atypical absence attacks, tonic, atonic, clonic and tonic-clonic attacks are included. A third group is proposed of generalized or focal seizures, which includes myoclonic seizures, inhibitory seizures (negative myoclonus) and spasms. The fourth group includes subtle seizures of the newborn. The fifth group contains unclassified seizures, emphasizing the need for video-EEG recordings which are essential for correct identification of the characteristics of the seizures and suitable classification in the corresponding epilepsy or epileptic syndrome.

Epilepsy↗

PubMed1997

[When and how should the long-term anti-epileptic treatment be stopped].

Although for some decades it has been customary to stop long-term treatment of epilepsy in patients who have been free of crises for several years, there is still no general agreement as to when, how and in which cases such treatment should be stopped. Several factors have to be taken into account when making such a decision: the known toxicity of anti-epileptic drugs; the fact that 10-20% of the patients on such treatment have recurrences of their epileptic crises and that around 25% of the children and 40% of the adults relapse when long-term treatment is stopped. On the other hand, factors which reduce the risk of relapse have recently been identified. When the psychological benefit of no longer having to take anti-epileptic drugs together with their high cost are also considered, it would seem advisable to stop treatment when the patient has had no epileptic crises for several years. Since there is no significant difference in the frequency of relapses when anti-epileptic drugs are suspended 2-5 years after the last crises, and these crises are more frequent when paroxystic activity is seen on the EEG before stopping the drugs, we recommend that treatment be stopped after 2 years free of crises in idiopathic epilepsy, after 3 years with no sign of abnormality in the EEG in patients with partial cryptogenic epilepsy and after at least 4 years without crises and 2 years of normal EEG in patients with partial symptomatic or generalized cryptogenic or symptomatic epilepsy. The criteria for suspending drug treatment should take account of the pharmacokinetic features and permit EEG control. Therefore we recommend that 40% of the total dose be stopped during the first 6 months at a rate of 20% every three months and then a further 20% every two months until medication has been stopped completely.

Anticonvulsants↗

PubMed1997

[Topiramate, a new antiepileptic drug].

OBJECTIVE: The characteristics of the new anti-epileptic drug topiramato (TPM) are described: multiple mechanism of action, favourable pharmaco-kinetics, wide therapeutic range and is relatively well tolerated, Development. Its initial usefulness in patients with partial crises resistant to other anti-epileptic drugs has been shown. TPM is equally effective in primary generalized crises, and in patients with the Lennox-Gastaut syndrome, in whom no problem of tolerance has been seen. CONCLUSION: TPM is a valuable drug for the treatment of epilepsy.

Anticonvulsants↗