Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Primidone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

Anticonvulsants for soman-induced seizure activity.

This report describes studies of anticonvulsants for the organophosphorus (OP) nerve agent soman: a basic research effort to understand how different pharmacological classes of compounds influence the expression of seizure produced by soman in rats, and a drug screening effort to determine whether clinically useful antiepileptics can modulate soman-induced seizures in rats. Electroencephalographic (EEG) recordings were used in these studies. Basic studies were conducted in rats pretreated with HI-6 and challenged with 1.6 x LD50 soman. Antimuscarinic compounds were extremely effective in blocking (pretreatment) or terminating soman seizures when given 5 min after seizure onset. However, significantly higher doses were required when treatment was delayed for more than 10 min, and some antimuscarinic compounds lost anticonvulsant efficacy when treatment was delayed for more than 40 min. Diazepam blocked seizure onset, yet seizures could recur after an initial period of anticonvulsant effect at doses </=2.5 mg/kg. Diazepam could terminate ongoing seizures when given 5 min after seizure onset, but doses up to 20 mg/kg were ineffective when treatment was delayed for 40 min. The GABA uptake inhibitor, tiagabine, was ineffective in blocking or terminating soman motor convulsions or seizures. The glutamate receptor antagonists, NBQX, GYKI 52466, and memantine, had weak or minimal antiseizure activity, even at doses that virtually eliminated signs of motor convulsions. The antinicotinic, mecamylamine, was ineffective in blocking or stopping seizure activity. Pretreatment with a narrow range of doses of alpha2-adrenergic agonist, clonidine, produced variable protection (40-60%) against seizure onset; treatment after seizure onset with clonidine was not effective. Screening studies in rats, using HI-6 pretreatment, showed that benzodiazepines (diazepam, midazolam and lorazepam) were quite effective when given 5 min after seizure onset, but lost their efficacy when given 40 min after onset. The barbiturate, pentobarbital, was modestly effective in terminating seizures when given 5 or 40 min after seizure onset, while other clinically effective antiepileptic drugs, trimethadione and valproic acid, were only slightly effective when given 5 min after onset. In contrast, phenytoin, carbamazepine, ethosuximide, magnesium sulfate, lamotrigine, primidone, felbamate, acetazolamide, and ketamine were ineffective.

Animals↗
PubMed2004

[Drug interactions with antiepileptic agents].

Drug interactions with antiepileptic agents are based in large part on pharmacokinetic mechanisms. Most prominent are induction or inhibition of enzymes of the cytochrome P450 (CYP) system, which is of central importance for metabolic elimination of lipophilic xenobiotics. Potent inductors of CYP isoenzymes are carbamazepine, phenobarbital, phenytoin, and primidone, thereby decreasing not only their own plasma levels and efficacy but also that of other antiepileptics and other drugs. Felbamate, oxcarbazepine, and topiramate are weak inductors of the CYP isoenzyme 3A4, whereas they inhibit CYP2C19. Valproic acid is a potent inhibitor of several CYP isoenzymes and glucuronyltransferases, resulting in an increase in plasma concentrations and toxicity of antiepileptics and other drugs. Antiepileptics that are not involved in drug interactions include gabapentin, levetiracetam, and vigabatrine. The P-glycoprotein may mediate the exit of antiepileptics from the brain. This transport mechanism is inhibited by carbamazepine, which may explain the enhanced clinical efficacy of a combination of carbamazepin with other antiepileptics. Other possible pharmacokinetic interactions are precipitation of antiepileptics in the stomach by antacids or sucralfate and displacement from plasmaprotein binding of one antiepileptic agent by another. Therapeutic drug monitoring (TDM) may be helpful in assessing pharmacokinetic drug interactions. Pharmacodynamic interactions appear to be responsible for the enhanced efficacy of antiepileptic combination therapy. In prescribing drugs, their spectrum of interactions has to be known.

Anticonvulsants↗
PubMed1994

[Anticonvulsant hypersensitivity syndrome to carbamazepine].

In a 39-year-old woman an anticonvulsant therapy was initiated because of focal attacks in the left arm and face. The patient experienced generalized maculopapular skin rashes in response to each of four chemically similar anticonvulsant drugs: phenytoin, carbamazepine, primidone and clonazepam. During administration of carbamazepine the clinical features included fever, hepatitis and hematological eosinophilia in addition to the skin rash (anticonvulsant hypersensitivity syndrome). The anticonvulsant hypersensitivity syndrome is defined as an idiosyncratic reaction caused by disturbed drug metabolism. Positive lymphocyte-transformation tests with carbamazepine and phenytoin indicate an immunological mechanism underlying the rashes in our patient. Patch testing with the four anticonvulsant drugs gave positive results only with carbamazepine. Skin biopsy showed the histological features of a delayed-type allergy. The anticonvulsant therapy was continued with a chemically unrelated preparation, valproic acid; this drug is well tolerated and has proved appropriate for prevention of seizures.

Adult↗
PubMed2002

Antiepileptic hypersensitivity syndrome: clinicians beware and be aware.

Antiepileptic hypersensitivity syndrome is a serious idiosyncratic, non-dose-related adverse reaction reported to occur with phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine. The reaction usually develops 1 to 12 weeks after initiation of therapy with one of the above agents and is recognized by the classic triad of fever, rash, and internal organ involvement. Immediate discontinuation of the suspected anticonvulsant is essential for good outcome. Patients usually are managed supportively with hydration, antihistamines, H(2)-receptor blockers, and topical corticosteroids. In severe cases, the use of systemic corticosteroids may be necessary. The use of intravenous immune globulin should be limited to severe cases where Kawasaki disease or idiopathic thrombocytopenic purpura cannot be ruled out. Education of health care professionals and patients is imperative to improving outcomes and prevention of this reaction in the future.

Anticonvulsants↗
PubMed2002

Management of essential tremor.

Essential tremor (ET) is the most prevalent tremor syndrome. It commonly affects the hands, head, voice, and other body parts. Appropriate management begins with correct diagnosis. Primidone and propranolol are the first-line medications for the treatment for ET, but several other medications may also provide benefit. In patients with medically refractory tremor, alternative therapies, including surgery or injections of botulinum toxin, may be considered.

Adrenergic alpha-Antagonists↗
PubMed2000

Primary Generalized Epilepsies.

For pure childhood absence epilepsy (CAE), ethosuximide (ESM) remains the drug of first choice. Although valproic acid (VPA) is of equal efficacy, it is more toxic, and is reserved for those patients with accompanying convulsions. Lamotrigine (LTG) is effective as both add-on and monotherapy for CAE. If any of these three drugs fails, one of the other two can be used as monotherapy. Rarely, when ESM, VPA, or LTG does not effectively control CAE, phenytoin (PHT), primidone (PRM), and phenobarbital (PB) may be partially effective, although carbamazepine (CBZ) may worsen absence seizures. Experience is limited with the newer AEDs. Tiagabine (TGB) may induce absence status epilepticus in PGE. Oxcarbazepine (OXC) and vigabatrin (VGB) may worsen absence seizures. Felbamate (FBM) is probably effective, but is potentially fatal. Lifelong therapy is not anticipated. For juvenile absence epilepsy (JAE), VPA is the drug of first choice. LTG is also of proven efficacy. The risks of VPA-induced teratogenicity (possibly lessened by the concurrent use of folic acid) and weight gain are potentially unacceptable in young women of childbearing age. Not enough data exists on the safety of LTG in pregnancy. A combination of VPA and LTG can be used if either drug alone is unsuccessful. For juvenile myoclonic epilepsy (JME), VPA is the traditional drug of first choice in most patients. As in JAE, side effects may make VPA an unacceptable choice in many patients, especially young women. In clinical practice, TPM is being increasingly used as monotherapy for JME. Many patients appreciate the accompanying weight loss seen with TPM, but it has potentially troubling side effects, has not been well studied as monotherapy for JME, and its safety in pregnancy has yet to be confirmed. PHT and CBZ may worsen myoclonus when used alone, but they may have a role as add-on treatment to VPA, LTG, or TPM, especially when generalized tonic-clonic seizures (GTCSs) are not controlled. PB and PRM may also be useful as add-on treatment, but often have unacceptable side effects. Clonazepam may be useful as adjunctive treatment for resistant myoclonic jerks. OXC and VGB both worsen myoclonic seizures. GBP is not useful in JME and can make seizures worse. The efficacy of FBM and TGB in JME is largely unknown. Lifelong AED therapy is necessary. In epilepsy with generalized tonic-clonic seizure (GTCS) on awakening (EGA), VPA is the drug of choice, especially if other seizure types (absence and myoclonic) are present. If only GTCSs are present, then PB, PHT, and CBZ may be as effective as VPA; however, the use of PHT and CBZ may "unearth" other seizure types (absence and myoclonic) in those patients with EGA, although PB is poorly tolerated. As for JME, LTG, and TPM may both be effective monotherapy for EGA, although the use of other AEDs in EGA has not been well studied. Lifelong AED treatment is necessary.

Journal Article↗
PubMed2002

Epilepsy in Pregnant Women.

For women of childbearing potential with epilepsy, seizures should be controlled with the smallest dosage of anti-epileptic drug (AED). Treatment with monotherapy should be achieved, if possible. The possibility of AED withdrawal should be considered in appropriate clinical setting prior to conception, and the AED treatment should be optimized prior to conception. Many pregnancies are unplanned, underscoring the need for constant vigilance in streamlining the treatment regimen. Prenatal counseling becomes particularly important, in order that both the physician and patient have open communication and realistic expectations about the course and outcome of a potential pregnancy. All women of childbearing potential with epilepsy should be informed about the known rates of teratogenicity of AEDs, possibility of increased seizure frequency during pregnancy, and the risks of the pregnancy and labor. All of the conventional AEDs are associated with an increased risk of major and minor anomalies in the offspring and are categorized as US Food and Drug Administration class C or D. Polytherapy increases this risk. Valproic acid and carbamazepine are each associated with an increased risk of neural tube defects, and should be avoided by women with a family history of spina bifida. This combination should be avoided, if possible. When a woman with epilepsy presents with pregnancy, a monotherapy regimen should not be changed if the seizures are well controlled. Reducing the number of AEDs can be considered in case of polytherapy, if the seizures are well controlled. If seizures are poorly controlled, adequate seizure control is the primary goal. Serum AED levels should be documented prior to conception, and within each trimester. More frequent monitoring may be necessary in case of poorly controlled seizures. If seizures have occurred during pregnancy, therapeutic AED levels should be documented in the late third trimester, prior to delivery. Phenytoin levels should also include an unbound fraction ("free" level); other unbound AED levels are not generally available. The dose adjustment should be made taking the whole clinical picture into account. Vitamin K 10 mg per day orally should be administered in the last 4 weeks of pregnancy for women taking hepatic enzyme-inducing AEDS (phenytoin, phenobarbital, primidone, carbamazepine, topiramate, and oxcarbazepine). The newborn should receive vitamin K 1 mg intravenously or intramuscularly regardless of maternal AED exposure.

Journal Article↗
PubMed2006

Essential tremor: treatment options.

The treatment of essential tremor depends on the tremor severity, location, and risk benefit ratios. Mild to moderate tremor usually will respond to oral agents such as noncardiac selective beta-blockers or primidone. Other agents including ethanol, topiramate, benzodiazepines, gabapentin, levetiracetam, and zonisamide may be effective. There are very little data comparing different oral agents, but there is support for polypharmacy in some cases. Botulinum toxin injections are effective in some tremor patterns, especially wrist flexion/extension and head tremor. For severe tremor, surgical lesioning or deep brain stimulation of the thalamus is justified and often dramatically improves function.

Journal Article↗
PubMed1983

DMCM: a potent convulsive benzodiazepine receptor ligand.

DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) is a very potent convulsant with high affinity for specific benzodiazepine binding sites. A number of compounds were compared for their ability to prevent seizures induced by DMCM and pentylenetetrazol. DMCM seizures were antagonized by benzodiazepine (BZ) receptor antagonists, such as Ro 15-1788, CGS 8216 and several beta-carboline-3-carboxylates, which all fail to inhibit pentylenetetrazol seizures. The benzodiazepines diazepam, clonazepam and lorazepam as well as valproate, ethosuximid, phenobarbital, primidone, diphenylhydantoin and carbamazepine antagonized both DMCM and pentylenetetrazol. Muscimol and gamma-vinyl-GABA did not inhibit DMCM seizures whereas THIP showed a weak and selective effect against DMCM. Valproate showed a relatively potent (60 mg/kg i.p.) and competitive antagonism of short duration. Baclofen antagonized DMCM at 3 mg/kg. Valproate and baclofen were at least 5 times more potent against DMCM-induced than against pentylenetetrazol-induced seizures. DMCM most probably induces the seizures by selective impairment of the functions mediated by the GABA/BZ receptor-chloride channel complex (inverse agonism) and therefore differs from GABA receptor blockers.

Animals↗
PubMed1986

Is amygdala kindling in rats a model for drug-resistant partial epilepsy?

Amygdala-kindled female rats were used to compare the effects of seven antiepileptic drugs that are clinically used for treatment of partial epilepsy with complex symptomatology, on generalized seizures, focal seizures, or electrographic seizure activity at the focus. As a second approach of drug evaluation, drug effects on mean latency, severity, and duration of the seizures were determined. Anticonvulsant potencies obtained were compared with those determined in the maximal electroshock seizure test in female rats. Phenobarbital, phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, but not primidone dose-dependently suppressed generalized motor seizures in kindled rats; however, except for the benzodiazepines, ED50S were substantially higher than those determined in the maximal electroshock seizure test. Compared with their effect on generalized motor seizures, all drugs were much less potent in blocking focal seizures and afterdischarges recorded from the amygdala. The data suggest that with respect to behavioral and pharmacologic characteristics of the amygdala kindling model, fully kindled rats may be a useful model for drug-resistant complex partial seizures with secondary generalization. Results of experiments with novel inhibitors of GABA uptake, which were inactive in the maximal electroshock seizure test but highly potent against kindled seizures, suggest that such drugs might be more effective than current antiepileptic drugs for treatment of partial epilepsy.

Animals↗
PubMed1992

Analysis of antiepileptic drugs in human plasma using micellar electrokinetic capillary chromatography.

We describe a method for the simultaneous determination of antiepileptic drugs (ethosuccimide, phenytoin, primidone, phenobarbital, carbamazepine and valproic acid) by micellar electrokinetic capillary chromatography using sodium dodecyl sulphate as the micellar phase. Factors affecting the micellar electrokinetic separation were studied for the quantitative determination of these drugs in human plasma. The confirmation of the peaks and the specificity of the method were investigated by combining multiwavelength detection with micellar electrokinetic capillary chromatography.

Anticonvulsants↗
PubMed1993

Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats.

Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.

Animals↗
PubMed1979

Effects of some anti-epileptic, neuroleptic and gabaminergic drugs on convulsions induced by D,L-allylglycine.

The antagonism of various seizure and time-related components of the convulsions resulting after IV injection of D,L-allylglycine into male Wistar rats were assessed in a standard test procedure. Trimethadione and ethosuximide did not antagonize the seizure components, whereas clonazepam, phenobarbital, diphenylhydantoin, primidone, valproate sodium, aminoxyacetic acid, etomidate, acetazolamide, flunarizine, pipamperone and baclofen did. The allylglycine test may thus represent a relatively specific method of differentiating between drugs effective against partial or generalized convulsive seizures from those effective against absence seizures. The neuroleptics haloperidol and pimozide were completely inactive in contrast to their reported antagonism of bicuculine seizures. The spectra of the active substances are discussed with respect to Principal Component and Cluster Analysis. Noteworthy are the similarities between baclofen and etomidate; between aminoxyacetic acid, phenobarbital and valproate sodium; and between diphenylhydantoin and flunarizine.

Allylglycine↗
PubMed1983

A spectrophotometric method for simultaneous estimation of phenytoin and carbamazepine.

A 0.5 ml sample of serum, containing different antiepileptic drugs, singly or in combination, was made alkaline, overlayered with isooctane, and steamed in the presence of KMnO4. The spectra of oxidized products in the organic layer were recorded in the UV range. Oxidized phenobarbitone and primidone show no absorption peak; diazepam a delta-max at 228 nm; phenytoin at 247 nm; and carbamazepine at 247 nm and 372 nm. Consequently, phenobarbitone and diazepam do not interfere in phenytoin quantitation, but carbamazepine does. The contribution of carbamazepine at 247 nm was calculated from the absorption at 372 nm and the ratio of its molar extinction coefficients at the two wave lengths. This was subtracted from the total A247 values to get the actual values due to phenytoin. Thus, a method for simultaneous analysis of carbamazepine and phenytoin in a single sample has been developed.

Carbamazepine↗
PubMed1984

Progabide as an add-on drug for epilepsy refractory to high dose antiepileptic drug therapy.

In a double-blind cross-over add-on trial an average daily dose of 2100 mg progabide or placebo were given for 3 months each as adjunctive therapy to 11 patients with intractable complex partial seizures uncontrolled by a high-dose regimen of either carbamazepine, phenobarbital, phenytoin or primidone. A reduction or an increase in seizure frequency by more than 50% was seen in one patient each. Mild transient sedative side effects were observed in two patients. The plasma concentrations of the concomitant antiepileptic drugs remained unchanged. Progabide appears to be as effective as primary antiepileptic drug for adjunctive therapy in partial epilepsy refractory to previous high-dose therapy. Progabide does not seem to be the drug urgently needed for failures of standard therapy despite its few side effects.

Adult↗
PubMed1986

Effects of antiepileptic drugs on concentration of serum proteins and immunoglobulins of epileptic patients.

Serum of normal volunteers and serum of epileptic patients receiving either a single drug or combined antiepileptic therapy with Phenytoin (Phen); Carbamazepine (Cbz); Primidone (Prim); Phenobarbital (Phb) were examined and showed: No differences with regard to total proteins, albumins and A/G ratio. The alpha 1-globulin fraction increased to 4.4% with Phen/Cbz (P less than 0.001) and decreased to 1.7% with Phen/Prim = (P less than 0.001). The alpha 2-globulins corresponded to 7.2% (P less than 0.001) with Phen/Prim and 15.5% (P less than 0.001) with Phen/Phb treatments. beta-Globulins decreased to 7.1% (P less than 0.05) when received Phen/Phb treatment. Low concentrations of serum gamma-Globulins were found in Phb (P less than 0.001), Prim (P less than 0.001, Phen (P less than 0.001) treated patients. However, with Cbz, Phen/Phb, Phen/Prim this electrophoretic fraction remained within the upper range of normal. IgA of patients treated with Phen showed a mean of 60 mg/dl. Those patients with Phen serum levels below or above 12-20 micrograms/ml remained normal. Prim and Phb treatment also decreased IgA. IgD was normal in patients treated with Phen/Prim. Alterations of immune humoral responses to all antiepileptic drugs were found.

Adolescent↗
PubMed1996

Liquid chromatographic assay in plasma of one of the members of a new series of anticonvulsants: D,L-3-hydroxy-3-ethyl-3-phenylpropionamide.

A method for the simultaneous determination of HEPP (D,L-3-hydroxy-3-ethyl-3-phenylpropionamide), a member of a new homologous series of phenylamide-derivative anticonvulsants, with six other antiepileptic drugs (ethosuximide, primidone, phenobarbital, phenytoin, carbamazepine and clonazepam) in plasma by high-performance liquid chromatography is described. These drugs are extracted from plasma by adding an equal volume of acetonitrile. An aliquot of the extract is then injected on a reversed-phase column with a acetonitrile-methanol-phosphate buffer mobile phase. The total time required for the whole analytical process, including the plasma pretreatment and chromatography, is approximately 30 min. The assay method is simple, rapid and reproducible, and therefore considered suitable for routine use in clinical investigations monitoring HEPP simultaneously with common antiepileptic drugs.

Acetonitriles↗
PubMed1996

Determination of apovincaminic acid in human plasma by high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic method is described for the quantitative analysis of low concentrations of apovincaminic acid (AVA) in blood plasma. AVA, interfering plasma components and primidone (used as the internal standard) were separated on a reversed-phase column of LiChrospher 60 RP-Select B (125 mm x 3 mm i.d.; 5 microns) (Merck). A UV-Vis detector was used at a wavelength of 254 nm. Each chromatographic separation was completed in 14 min and the results showed a relative recovery which varied between 95.9 and 116%, a good overall precision (relative standard deviation, 7.00%) and sensitivity over a linear range of 5.00-300 ng ml-1 (R = 0.999) for AVA in plasma. The method was applied to the analysis of plasma samples obtained from healthy subjects treated with one single oral dose of 20 mg of vinpocetine. The results indicate the method to be suitable for pharmacokinetic studies.

Administration, Oral↗