Despite the recent entry into the market-place of a range of new pharmacological treatments for epilepsy, most patients still receive the standard antiepileptic drugs. This review considers the clinical place and practical use of these agents. Detailed consideration is given to carbamazepine, phenytoin, sodium valproate, phenobarbital and ethosuximide, with lesser emphasis on primidone, clobazam and clonazepam. Individualization of therapy, polypharmacy, refractory epilepsy, therapeutic drug monitoring, pregnancy, withdrawing treatment, epilepsy prophylaxis and referral to an epilepsy centre are also discussed. The paper concludes with a statement of 12 basic rules in prescribing established antiepileptic drugs.
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Concentrations of carbamazepine, phenytoin, phenobarbital, and primidone have been measured by high pressure liquid chromatography (HPLC) in serums of 177 Sri Lankan epileptic patients. Relationships between concentrations and dose per kg body weight of these drugs have been compared with those of patients in the Netherlands, using a matching procedure. Although variabilities in dose-concentration ratios were somewhat larger in Sri Lanka than in the Netherlands, no evidence was found of a systematic difference in pharmacokinetics between both populations.
The antiepileptic activity of oral frusemide (120 mg daily) was compared with that of an identical placebo in a double-blind crossover trial in fourteen patients with severe focal epilepsy who were receiving long-term therapy with established antiepileptic drugs. A statistically significant reduction in the frequency of focal fits was seen with the active drug. Marked drowsiness occurred in three patients during frusemide therapy, causing their withdrawal from the trial. A slight, but significant, rise in serum phenobarbitone concentrations was observed during frusemide therapy, but no change was seen in serum primidone or phenytoin concentrations. Frusemide significantly lowered plasma sodium and potassium concentrations, and increased plasma bicarbonate.
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Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially life-threatening allergic disorder, which is well described in relation to many aromatic anticonvulsants. Lamotrigine is a relatively new aromatic anticonvulsant agent that is thought to act on voltage-dependent sodium channels. Initially, it was licensed as add-on therapy for seizures inadequately controlled by other medications. However, its use has been broadened to other indications, including stand-alone therapy for seizures as well as for bipolar disorder. There is extensive experience with hypersensitivity syndromes related to phenytoin, carbomazepine, primidone, and phenobarbital, but fewer reactions have been reported to lamotrigine because of its relatively recent release. Patients with human immunodeficiency virus (HIV) have a higher rate of adverse reactions to many medications. It is unknown if they react more commonly to anticonvulsants such as lamotrigine. It is also unknown if the syndrome lias a tendency to be more severe or prolonged in such patients. The diagnosis of AHS may be particularly elusive in patients with HIV because its common features can easily be confused with an infectious etiology. We report the occurrence of a prolonged hypersensitivity syndrome likely related to lamotrigine in a 32-year-old female with HIV and review the literature regarding this condition.
Serum iodothyronine concentrations were measured in patients on long-term therapy with one or two anticonvulsant drugs. Diphenylhydantoin (DPH) and carbamazepine (CBZ) reduced the serum levels of thyroxine (T4) free T4 index, reverse triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2), whereas the depressant effect on the serum levels of triiodothyronine (T3) and free T3 index was small but statistically significant. In patients administered DPH and phenobarbital (PB) or CBZ and primidone (PD) the serum iodothyronine levels were also depressed, except for normal T3 and free T3 index. Patients receiving only PB or PD had normal serum levels of total and free thyroid hormones, but decreased concentrations of rT3 and 3,3'-T2. Only supratherapeutic concentrations of DPH and CBZ added in vitro to control sera significantly reduced the number of T4 and T3-binding sites, as reflected in increased T4 and T3 uptake test results. This indicates that the DPH and CBZ-induced decrease in thyroid hormone concentrations in vivo is not due to a displacement of thyroid hormones from their binding sites on serum proteins. The antidepressant drugs amitriptyline and mianserin had no effect on the thyroid hormone levels in serum.
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Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are well-established treatments in clinical practice, they may be ineffective in 25% to 55% of patients and can produce serious adverse events in a large percentage of them. For these reasons, it is worth evaluating the treatment alternatives for essential tremor. Some specialists have suggested that pregabalin could be a potentially useful agent, but there is uncertainty about its efficacy and safety.
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To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.
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Neonatal intensive care unit.
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In the very rare cases where a pregnancy occurs during oral contraceptive use, the blame is usually laid against the patient for having forgotten to take the pill. Evidence has started to accumulate to suggest that neither the patient nor the pill is at fault in some contraceptive failures. It may be because the patient is taking other medicines and these may be preventing the pill from suppressing ovulation. Most drug interactions reducing or negating contraceptive activity are due to concomitant use of drugs having microsomal enzyme-inducing activity (e.g., some antibiotics, especially rifampicin, and anticonvulsants, including phenobarbital, phenytoin, and primidone. Other antibiotics (e.g., tetracycline) may also interact by interruption of the enterohepatic circulation of contraceptive steroids. Less well appreciated, oral contraceptive steroids may themselves modify the metabolism and pharmacological activity of various other drugs (e.g., anticoagulants, benzodiazepines, beta-blockers, caffeine, corticosteroids, and tricyclic antidepressants); in this respect the oral contraceptives are acting as enzyme inhibitors. Contraceptive steroids may also interact with drugs that cause enzyme inhibition and this delays the metabolism of the hormonal agents. Interactions of this type would be expected to potentiate the action of the contraceptive steroids. It is suggested that the effects of such interaction might be presented in terms of increased incidence of side effects, including water retention, diabetogenic effects, hypertension, and an increased risk of thromboembolic disorders. The spectrum of interactions with oral contraceptives is presented in three tables.
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Task-specific tremor is a form of action tremor that occurs only or mainly when a person is performing a specific skilled task. The most frequently encountered form of task-specific tremor is primary writing tremor (PWT). Currently, there is debate about whether PWT is a variant of essential tremor, writer's cramp (dystonia), a separate entity, or in some cases related to essential tremor and in others to dystonia. PWT typically occurs at a frequency of 5-7Hz and has been subdivided into to two types: Type A, task-induced tremor, and type B, positionally sensitive tremor. Temporary suppression of the tremor by alcohol is seen in about one-third of cases. There are no randomized controlled therapeutic studies involving patients with PWT, although anecdotal reports of beneficial responses to propranolol, primidone, anticholinergics, botulinum toxin treatment, and stereotactic surgery have been reported. Reciprocal inhibition of the H-reflex and intracortical excitability are normal in PWT, unlike writer's cramp. Hyperactivity in the cerebellar hemispheres has been demonstrated with positron emission tomography in PWT. Other task-specific tremors have been described but have not been studied in detail.
In 36 epileptic children treated with primidone alone or in combination with additional anticonvulsants, salivary drug levels were compared in resting (I) and in flow-stimulated (II) saliva and were related to the corresponding serum levels. Primidone levels in saliva I and saliva II were highly correlated (r = 0.97) but were significantly (p less than 0.001) lower in saliva II; the mean difference was -38%. Serum primidone levels were highly correlated to salivary primidone levels both in saliva I (r = 0.92) and in salvia II (r = 0.91). A significant negative correlation could be established between the salivary flow rate and the saliva/serum ratio of primidone, especially in saliva I (r = 0.61; p less than 0.001). The mean saliva I/serum ratio was 1.115, reflecting drug accumulation in resting saliva. The reason primidone accumulates remains unclear. When salivary flow was stimulated, the mean saliva/serum ratio decreased to 0.7, indicating the development of a drug concentration slope from blood to saliva. This is explained by the limited permeation of the drug through cellular membranes due to its rather low lipid solubility. From the data it can be concluded that saliva is suitable for monitoring primidone levels provided the conditions of sample collection are standardized.
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Twenty patients with tongue tremor associated with essential tremor are reported. Patients were unaware of the tongue tremor, and voice disturbance was a complaint in only one patient. Three patients had an isolated tongue tremor. Hand tremor was present in 16 patients. Dystonia, myoclonus, and tremor of other body parts were present in some patients. Three patients had a mild-to-moderate dysarthria. The frequency of tongue tremor (4-8 Hz) was identical to hand tremor. The intravenous infusion of ethanol suppressed tongue tremor. Therapy with propranolol, primidone, or clonazepam also reduced tongue tremor amplitude. Tongue tremor is a common finding in some essential tremor patients but often there are no symptoms.
Essential tremor is one of the most frequent movement disorders. It is characterized by postural and action tremor that may affect different regions of the body. Among current treatments propranolol and primidone are included. However, these two drugs have demonstrated a limited efficacy and several adverse events. Additionally, they are contraindicated in patients with cardiac insufficiency and several respiratory diseases. New antiepileptic drugs are revealing as a possibility in the treatment of this disease. AIM. To evaluate efficacy and tolerability of zonisamide in the treatment of essential tremor.