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Biomedical subjects

J K Penry

Publications and source records attributed to J K Penry.

At least 55 records · Page 3Linked to original sources
PubMed1981

Epilepsy in adults.

The past decade has seen advances in the management of patients with epilepsy. The development of practical long-term electroencephalographic techniques, with or without simultaneous video recording, has increased the accuracy of diagnosis of seizure types. The technique also provides clinicians and investigators with a method for establishing the clinical efficacy of antiepileptic drugs and determining their therapeutic serum concentrations. Computerized tomography has enhanced the identification of structural brain lesions. Most of the reported CT abnormalities consist of diffuse and focal atrophies, mild ventricular dilatations, and porencephalies. CT has detected tumors in 8 to 10% of the patients regardless of age or type of seizure involved. New concepts of antiepileptic drug therapy have developed from the recognition of pharmacological properties peculiar to each agent. Determination of serum antiepileptic drug levels has to be utilized to reduce the problem of pharmacokinetic variability from one patient to another and in the same patient at different times, so that dosage can be individualized to achieve maximum therapeutic effects with least toxicity. Review of the literature on pregnancy in epileptic women shows that a third to half experienced more seizures during gestation. Reduced serum levels of most antiepileptic drugs have recently been observed during gestation. Infants of epileptic women taking antiepileptic drugs have a two to three times greater risk for congenital anomalies than infants of nonepileptic women. However, with the exception of oxazolidinediones, evidence to date has not proved the teratogenicity of antiepileptic drugs. The role of genetic factors and the effect of seizures during pregnancy have not been determined. Modest progress has been made in epilepsy rehabilitation, but serious problems still remain. The unemployment rate of persons with epilepsy is twice the national average. Half of those who are successfully employed did not disclose their disorder at the time of employment. Several prognostic indicators have been reported, but the validity of many of these indicators is questionable. For example, does shorter life expectancy apply to all subgroups, or does it vary according to seizure type and cause? The life expectancy, treatment response, and probability of remission in epileptic persons must be reevaluated after consistent applications of current methods of epilepsy management.

Abnormalities, Drug-Induced↗
PubMed1981

Mechanism of valproate-phenobarbital interaction in epileptic patients.

Valproate effects on phenobarbital biodisposition were examined in a search for the mechanisms of the valproate-induced elevation of plasma phenobarbital during antiepileptic therapy. The study involved patients who were treated with phenobarbital alone and phenobarbital plus valproate. Several kinetic parameters were determined after a pulse dose of stable isotope-labeled phenobarbital, with plasma phenobarbital levels at a steady state. Plasma elimination of labeled phenobarbital was studied by selected ion monitoring. The addition of valproate to the phenobarbital regimen resulted in elevation of plasma phenobarbital and increase in urinary output of unchanged phenobarbital. There was no effect on urinary pH. The rise in plasma phenobarbital was paralleled by lengthening of phenobarbital elimination half-life while the decrease of plasma phenobarbital clearance paralleled the decrease in phenobarbital elimination rate constant. These findings suggest that inhibition of phenobarbital metabolism by valproate is the mechanism for this clinically important drug-drug interaction.

Adolescent↗
PubMed1981

Reduction of steady-state valproate levels by other antiepileptic drugs.

Steady-state plasma valproate (VPA) levels were analyzed in 37 children after 6 weeks of VPA therapy. Twenty-six patients were receiving other antiepileptic drugs in addition to VPA (experimental group). Eleven patients who received VPA alone served as controls. The mean VPA dose was not statistically different for the two groups (experimental group, 35.4 mg/kg/day, 11.6 SD; control group, 31.1 mg/kg/day, SD 6.6) The mean plasma VPA level was significantly lower for the experimental group (63.0 micrograms/ml, SD 21.8) than for the control (99.3 micrograms/ml), SD 23.3) (p less than 0.01). VPA level: dose ratio (LDR) was also reduced in the experimental group (1.92, SD 0.75) as compared to controls (3.26, SD 0.65) (p less than 0.01). Within the experimental group the VPA levels and VPA LDR were significantly reduced in patients receiving either phenytoin or phenobarbital. The data suggest that other antiepileptic drugs significantly alter the steady-state level to dose relationship for VPA.

Adolescent↗
PubMed1981

Adverse effects of phenytoin on peripheral nerves and neuromuscular junction: a review.

Review of the literature shows that long-term phenytoin therapy is associated with peripheral neuropathy and neuromuscular disorder that rarely can be symptomatic. The usual manifestations of the peripheral neuropathy are lower extremity areflexia, sensory deficits, and reduced conduction velocities. The risk for these peripheral nerve abnormalities is greater with increased serum levels or long duration of therapy (usually more than 5 years). The relative risks according to age groups or number and kinds of antiepileptic drugs used are undetermined. It is not known if detected abnormalities are static or slowly progressive. Isolated case reports have claimed the resolution of signs and symptoms after discontinuance of therapy or correction of a state of intoxication. Appropriate measures to prevent the appearance or progression of the complications are discussed in light of the available evidence.

Action Potentials↗
PubMed1981

The hospital experience and seizure control.

We studied 30 patients who were admitted to the hospital because of intractable seizures. Twenty-three had fewer seizures during one or both of the first 2 hospital weeks than before admission, although medication was not changed. The role of environment in seizure control is difficult to measure, but hospital admission itself is a form of environmental manipulation. When seizure control is achieved in the hospital, the hospital experience itself must be considered in addition to other therapeutic interventions.

Anticonvulsants↗
PubMed1980

The development of tolerance to the anticonvulsant effect of phenobarbital in mice.

The development of tolerance to the anticonvulsant effect of chronically administered phenobarbital was demonstrated in mice by the maximal electroshock (MES) test. Anticonvulsant activity decreased 50% over a 5 day period. Brain and plasma levels of phenobarbital measured 2 hr after a 25 mg/kg dose of phenobarbital were the same between days 1 and 5, indicating that distributional or pharmacokinetic parameters were not involved. The loss of anticonvulsant activity of phenobarbital is primarily related to the drug's effect to prevent the spread of MES-induced epileptic neuronal activity. In contrast, the anticonvulsant action of phenobarbital on seizure threshold, as measured by the minimal electroshock seizure threshold (EST) test, and on the spread of epileptic discharge induced by pentylenetetrazol (PTZ), as evaluated by the PTZ infusion test, remained unchanged.

Animals↗
PubMed1980

Catamenial epilepsy: a review.

This review of 126 reports on catamenial epilepsy describes seizure exacerbations associated with the menses. The importance of hormonal measurements, the influence of antiepileptic drugs and oral contraceptives, and the significance of hormonal changes on epilepsy are evaluated. The EEG changes during menses are discussed. Explanations for conflicting data are offered, and potential future investigations on catamenial epilepsy are suggested.

Adult↗
PubMed1980

Sodium valproate: pharmacokinetics and effectivensss in treating intractable seizures.

Sodium valproate (VPA) was first marketed in the United States in 1978. In this pilot study of pharmacokinetics and toxicity, VPA was added to the treatment regimens of 20 patients (10 adults and 10 children) with intractable seizures. The drug was absorbed and excreted rapidly; the mean half-life was 9.6 hours. Drowsiness and gastrointestinal symptoms were the most common side effects, but they were usually minor and transient. An increase in some plasma phenobarbital levels and a decrease in some plasma phenytoin levels were attributed to drug interaction. Control of absence attacks was assessed by 12-hour telemetered electroencephalograms. Sodium valproate was most efficacious in generalized seizure disorders, particularly absence seizures.

Adolescent↗
PubMed1979

Plasma concentrations of phensuximide, methsuximide, and their metabolites in relation to clinical efficacy.

The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.

Drug Evaluation↗
PubMed1979

The use of antiepileptic drugs.

The use of antiepileptic drugs has become increasingly effective through several factors: new techniques that allow better diagnosis of the seizure disorder and its underlying cause; the development of new medications and increased knowledge of old ones; and the widespread use of antiepileptic drug-level determinations. The choice of a drug depends heavily on an accurate diagnosis of seizure type, which may determine the response to the medication. Because of better diagnostic criteria and intensive monitoring procedures, the correct seizure disorder can be more easily diagnosed and, therefore, the proper medication selected. Minimal efficacious and toxic blood concentrations have now been identified for most antiepileptic drugs. Several, including primidone, carbamazepine, methsuximide, and mephenytoin, have pharmacologically active metabolites that affect both the toxicity and efficacy of the prescribed drug and can now be measured in the plasma. The most effective use of the antiepileptic drugs depends on a combination of reliable blood level measurements, clinical observation, and knowledge of their pharmacokinetics and biotransformation.

Anticonvulsants↗
PubMed1978

Effects of ethanol, caffeine, and placebo on the auditory evoked response.

A previous paper (Wolpaw and Penry 1975) described separation of the 75-250 msec portion of the AER into N1P2, a product of large areas of cortex, and the T complex, probably a product of secondary auditory cortex. With monaural stimulation, the T complex is larger and earlier on the side contralateral to stimulation and on the right side. Thirty-one normal adults received 3 oz. of ethanol, 300 mg of caffeine, or placebo. Monaural AERs were recorded before intake in all cases, 1 and 4 h after ethanol and 80 min after caffeine or placebo. Blood levels of ethanol and caffeine were measured. Placebo produced mild (20%) decreases in N1P2 amplitude. Caffeine did not decrease N1P2 amplitude. It did produce a statistically significant 2% decrease in Ta peak latency. Ethanol reduced N1P2 amplitude markedly at 1 h and mildly at 4 h. Placebo did not affect hemispheric differences. Caffeine significantly increased the Ta peak ipsilateral vs. contralateral latency difference in 3 of 7 individuals. Ethanol significantly increased it in 3 of 6 subjects at 1 h and in 7 of 10 at 4 h, primarily by increasing ipsilateral latencies.

Adult↗