RESUMO
A case of acute primidone intoxication, due to overdose, was evaluated at National Taiwan University Hospital. Serial assessment of the clinical manifestations, electroencephalograms and serum levels of primidone and phenobarbital were made. From these data, we conclude that the toxic effects, such as depression of the central nervous system and dysequilibrium, are due mostly to primidone itself, rather than its metabolite, phenobarbital.
Assuntos
Primidona/envenenamento , Adulto , Sistema Nervoso Central/efeitos dos fármacos , Overdose de Drogas/sangue , Overdose de Drogas/diagnóstico , Eletroencefalografia , Humanos , Masculino , Fenobarbital/sangue , Primidona/sangueRESUMO
Seven cases of crystalluria following primidone overdose have been reported since the 1950s. An eighth case of primidone crystalluria following overdose is presented. Because of low aqueous solubility (600 mg/L at 37 degrees C) which is directly proportional to temperature, any factor increasing renal excretion of unchanged primidone predisposes to crystal formation. Renal clearance is dependent on dosage because of negligible protein binding, zero-order conversion to phenobarbitone (phenobarbital) and first-order conversion to phenylethylmalonamide. Therapy with other anticonvulsants known to induce the metabolism to phenobarbitone does not appear to be protective against crystalluria in overdose situations. The critical serum primidone concentration for crystalluria presence seems to be 80 mg/L. There is evidence for nephrotoxicity of the crystals themselves if formed in vivo (actual crystal presence during voiding). The chemical phenomenon of supersaturation of a solution is protective against in vivo crystal formation with subsequent nephrotoxicity. Vigorous hydration to augment elimination and to lessen the propensity for renal toxicity is recommended.
Assuntos
Primidona/envenenamento , Doenças Urológicas/urina , Adulto , Cristalização , Feminino , Humanos , Rim/efeitos dos fármacos , Primidona/farmacocinética , Primidona/urinaRESUMO
The present paper describes a patient who was in danger of dying from a massive primidone overdose. She was comatose, hypotensive and in acute renal failure with crystalluria. Because of her clinical condition and high plasma primidone level (209 mg/l) haemoperfusion was instituted. Both the calculated drug clearances and the remarkable improvement in the patient's clinical condition suggest that haemoperfusion was very effective.
Assuntos
Coma/induzido quimicamente , Hemoperfusão , Primidona/envenenamento , Idoso , Carvão Vegetal/uso terapêutico , Coma/terapia , Feminino , Meia-Vida , Humanos , Cinética , Fenobarbital/sangue , Feniletilmalonamida/sangue , Primidona/metabolismoRESUMO
Serial plasma levels of phenytoin, primidone, and phenobarbital were determined in a patient following massive overdose of phenytoin and primidone. The patient's neurologic status improved slowly over a period of 10 days and correlated best with the rise and fall of phenytoin plasma concentrations. The pharmacokinetics of all three agents were characterized by nonlinear regression analysis of their respective plasma concentration-time profiles during the elimination phase, followed by analog computer simulations of their entire plasma concentration-time profile closely resembled the observed values. Average values of Km and Vmax obtained from patients undergoing chronic therapy were used in the simulation and appear to adequately describe phenytoin elimination in this overdose situation. The elimination half-lives of primidone and phenobarbital of 6.2 and 83.5 hours, respectively, were within the "normal range" for patients on chronic therapy. Two distinct absorption phases for primidone and three for phenytoin were noted. The marked decrease in the estimated absorption rate constant between phases 1 and 2 for each drug may have been due to slow dissolution of a large congealed mass of phenytoin and primidone in the gut. The analysis of serial plasma samples following a massive overdose is recommended to provide a reliable data base for therapeutic decisions.
Assuntos
Doenças do Sistema Nervoso/induzido quimicamente , Fenitoína/envenenamento , Primidona/envenenamento , Adulto , Humanos , Cinética , Masculino , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangueRESUMO
Primidone (PRIM) is metabolized into phenobarbital (PB) and phenylethylmalonamide (PEMA). During anticonvulsant therapy with PRIM under normal conditions PB represents by fat the largest portion of the total concentration of all three components (PRIM + PB + PEMA). In combined therapy with diphenylhydantoin (DPH), and during chronic PRIM overdosage, the relative concentration of PB is even higher. A case of renal insufficiency while on PRIM therapy and a case of acute PRIM intoxication are presented. In both cases PRIM and PEMA are elevated while PB is relatively low. The mechanisms involved in this phenomenon are discussed. Excluding young children with chronic PRIM overdosage, and the endogenous and exogenous intoxication described here, a relative PB concentration below 40% indicates a lack of patient compliance if a steady treatment schedule has been maintained for at least 3 weeks.
Assuntos
Falência Renal Crônica/metabolismo , Primidona/metabolismo , Doença Aguda , Adulto , Idoso , Biotransformação , Feminino , Humanos , Fenobarbital/sangue , Feniletilmalonamida/sangue , Primidona/sangue , Primidona/envenenamento , Tentativa de SuicídioRESUMO
Pupillary hippus was observed and recorded in a man of 44 years, who had epileptic seizures, chronic alcoholism with liver disease and Primidon intoxication, during a period of unconsciousness of 24 h. During this time the simultaneous records of the EEG and pupillogram over a long period of time revealed that the basic EEG rhythm and hippus had the same frequency. Both recordings were temporarily in phase, time-locked, and could be blocked by painful and acoustic stimuli. The etiology and interpretation of hippus are discussed.
Assuntos
Atetose/diagnóstico , Pupila , Adulto , Alcoolismo/complicações , Eletroencefalografia , Epilepsia Tônico-Clônica/complicações , Humanos , Masculino , Primidona/envenenamento , InconsciênciaRESUMO
We have encountered a case of apparent intoxication with primidone (Mysoline) in a patient with severe renal impairment. Of interest were high serum levels of phenylethyl-malondiamide (PEMA), a metabolite of primidone.
Assuntos
Malonatos/envenenamento , Feniletilmalonamida/envenenamento , Primidona/envenenamento , Adulto , Biotransformação , Feminino , Meia-Vida , Humanos , Feniletilmalonamida/sangue , Primidona/sangue , Primidona/uso terapêutico , Esclerose Tuberosa/sangue , Esclerose Tuberosa/tratamento farmacológicoRESUMO
An 18 year old girl is reported, who ingested 15 g of primidone (Liskantin), 330 mg/kg, to commit suicide. Continuous monitoring of the serum levels of primidone, PEMA, and phenobarbital revealed increased elimination of primidone by forced diuresis (6000 ml/24 hours). It is concluded that forced diuresis inhibits the otherwise mandatory increase in primidone metabolites, PEMA and phenobarbital. It is suggested that even after improvement of the clinical symptoms forced diuresis should be continued for at least 48 hours. In epileptic patients the reinstitution of primidone therapy should be considered only on the third day after accidental ingestion, if the clinical symptoms have improved, and if there is no possibility of immediate determination of primidone serum levels.
Assuntos
Primidona/envenenamento , Adolescente , Diurese , Feminino , Humanos , Fenobarbital/urina , Feniletilmalonamida/urina , Primidona/sangue , Primidona/metabolismoRESUMO
A novel metabolite, alpha-phenyl-gamma-butyfolactone has been isolated in urine samples of patients severely intoxicated by either glutethimide, phenobarbital, or primidone. This lactone was prepared synthetically and its spectral data and chromatographic properties were compared to those data obtained from the urine samples of drug overdosed victims. The results of these comparisons confirm the presence of this lactone in human urine following the ingestion of large amounts of the parent drug.
Assuntos
Glutetimida/metabolismo , Fenobarbital/metabolismo , Primidona/metabolismo , Glutetimida/envenenamento , Humanos , Fenobarbital/envenenamento , Primidona/envenenamentoRESUMO
We describe a case of fatal overdosage with primidone and methsuximide. During the early phase of the patient's hospital course we found concentrations of methsuximide, N-desmethylmethsuximide, and primidone in serum that far exceeded the usual therapeutic concentrations, as determined by gas-liquid chromatography. Determination of N-desmethylmethsuximide in peritoneal fluid demonstrated concentrations comparable to those in serum. This led to the therapeutic decision to manage the patient by dialysis. Subsequently, serum samples collected during the course of hospitalization were analyzed quantitatively by gas-liquid chromatography for methsuximide, N-desmethylmethsuximide, primidone, phenobarbital, and diphenylhydantoin. Selected serum specimens were also analyzed by gas chromatography-mass spectrometry, and N-methyl-2-hydroxymethyl-2-phenylsuccinimide, a metabolite of methsuximide not previously described in human serum, was identified by analysis of its mass spectrum.
Assuntos
Primidona/envenenamento , Succinimidas/envenenamento , Adulto , Computadores , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Microquímica , Fenobarbital/sangue , Fenitoína/sangue , Primidona/sangue , Succinimidas/sangue , Succinimidas/metabolismoRESUMO
A patient admitted to the hospital in coma was found to have massive primidone crystalluria. Gas chromatographic analysis of blood and urine for primidone and phenobarbital showed high urine primidone levels and high blood phenobarbital levels. The primidone levels suggest that primidone is rapidly cleared into urine. The high blood phenobarbital levels within 12 hr of overdosage with a history of diphenylhydantoin therapy and without phenobarbital therapy or overdosage suggests that diphenylhydantoin may influence the metabolic conversion of primidone to phenobarbital. The relationship of clinical symptomatology to high levels of primidone and phenobarbital is unclear. Analysis of blood and urine for primidone and phenobarbital and urine for crystals is of value in establishing diagnosis and prognosis in cases of suspected primidone overdosage.