Biomedical subjects

H Kutt

Publications and source records attributed to H Kutt.

At least 55 records · Page 3Linked to original sources

PubMed1979

An improved gas-liquid chromatographic procedure for the determination of amitriptyline and nortriptyline levels in plasma using nitrogen-sensitive detectors.

An improved gas-liquid chromatographic procedure for the plasma level determination of amitriptyline and nortriptyline using nitrogen-sensitive detectors is described. Derivatization of the secondary amines using trifluoroacetic anhydride greatly improves the response and reproducibility of the assay. Plasma samples containing as little as 5 ng/ml of amitriptyline and nortriptyline can be assayed precisely and reproducibly, using protriptyline as internal reference standard.

Amitriptyline↗

PubMed1979

Seizure disorders and trace metals: manganese tissue levels in treated epileptics.

We determined the concentrations of manganese in whole blood and hair in 52 epileptics, 6 blood relatives, and 24 normal controls. Blood, and possibly hair manganese content, was significantly lower in treated epileptics than in controls (p less than 0.002). Although not all patients showed reduced tissue manganese levels, most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity. These differences in manganese levels were not correlated with the type, dose, or plasma levels of anticonvulsant medication. Reduced manganese availability at the neuronal level, where Mn++ stabilizes membrane excitability, may affect epileptogenic lesions to increase the likelihood of seizure activity.

Adolescent↗

PubMed1979

Monitoring diazepam and desmethyldiazepam concentrations in plasma by gas-liquid chromatography, with use of a nitrogen-sensitive detector.

We describe a modified [from Anal. Chem. 36, 2099 (1964)] procedure for determining diazepam and its pharmacologically active metabolite, desmethyldiazepam, in plasma, with use of a nitrogen-sensitive detector in the gas-liquid chromatography. We used medazepam as the internal reference standard. Diazepam and desmethyldiazepam are converted to their respective benzophenones by mineral acid hydrolysis. With this procedure, as little as 100 muL of plasma can be used to determine the drug in concentrations as low as 10 microgram/L, accurately, reproducibly, and quickly. Within-run and between-run CVs for 100 microgram/L concentrations of the two compounds were 5 and 7%, respectively.

Chromatography, Gas↗

PubMed1978

Correlation of the "EMIT" with a gas-liquid chromatographic method for determination of antiepileptic drugs in plasma.

We report a study of the comparison of antiepileptic drugs (phenobarbital, phenytoin, primidone, and carbamazepine) by the Enzyme Multiplied Immunoassay Technique "EMIT" and the gas chromatography (GLC) method. Overall, reasonable correlations were observed for all of the above-mentioned assays by both methods in the majority of samples included in this study. Our observations for statistical and clinical differences at various levels of phenobarbital and phenytoin are discussed. A suggestion is provided in order to avoid a major discrepancy (approximately 30% higher values by EMIT vs GLC) in results observed from the "Bottom of the Bottle Effect" for EMIT reagent.

Anticonvulsants↗

PubMed1977

Pharmacological prophylaxis against the development of kindled amygdaloid seizures.

The kindling of amygldaloid and cortical seizures in cats was used to study the prophylactic effects of phenobarbital, phenytoin, ethosuximide, acetazolamide, and dexamethason. Phenobarbital prevented the evolution of such seizures beyond stage 4 in all amygdaloid-kindling animals during 160 days of study. The prophylactic effect persisted on periodic challenge after the drug had been discontinued. Phenytoin, ethosuximide, acetazolamide, and dexamethasone appeared to have no prophylactic effect against the development of kindled amygdaloid seizures. With cortical kindling, both phenobarbital and phenytoin retarded the evolution of seizures without achieving true prophylaxis. The drugs appeared to act as suppressants. Prophylaxis was not an "all-or-none" phenomenon but rather a limitation of the stage of seizure evolution.

Acetazolamide↗

PubMed1977

Anticonvulsivant-induced depression of clotting factors in children.

A few neonates born to mothers receiving anticonvulsant drugs during pregnancy have shown defects in vitamin K dependent clotting factors with or without clinical bleeding. Experimentally, phenytoin (diphenyl hydantoin, DPH) has induced clotting defects in cats and inhibited production of clotting factors in rat liver slices. Phenobarbital has produced similar but milder defects. Anticonvulsants have been observed to produce clotting defects in 9 children, 2 weeks to 8 years in age. Elevated levels of phenytoin or other anticonvulsants, or a combination of anticonvulsants were measured in the children. Six patients were on drug combination including two or more of the following: phenytoin, phenobarbital, primidone, carbamazepine, diazepam, ethosuximide. Clotting defects included: elevated prothrombin time, elevated partial thromboplastin time, diminished factors V, VII or X. All children had neurologic symptoms of anticonvulsant toxicity, but the only hematologic problems were oozing from venipuncture sites and increased bruising in 3. All patients were on normal diets and had normal liver function tests. By lowering the level of anticonvulsants, clotting factors returned toward normal. Elevated levels of anticonvulsants can potentially produce clotting defects in neonates and young children.

Anticonvulsants↗

PubMed1975

Interactions of antiepileptic drugs.

Several interactions involving antiepileptic drugs are based on changes in the rate of their metabolism and elimination, with concomitant rise or fall of plasma levels. Thus, phenobarbital generally induces the production of the DPH metabolizing enzyme, but its presence inhibits the action of that enzyme. The net result depends upon the balance between these factors in individual patients. Either a decline, a rise, or no change of the DPH plasma level may occur after the onset of administration of phenobarbital. Drugs that may cause elevation of the DPH plasma level include disulfiram, sulthiame, bishydroxycoumarin, chloramphenicol, phenyramidol, benzodiazepines, sulfamethizole, and isoniazid. Isoniazid has been shown experimentally to be a strong inhibitor of DPH metabolism. The extent of DPH plasma level elevation by INH is related to the genetic make-up of individual patients. The highest and frequently toxic DPH plasma levels were seen in very slow INH inactivators. The incidence of clinically significant interactions is not high with most drug combinations; marked changes of antiepileptic drug levels occur only in apparently susceptible individuals. The effects of interactions are not necessarily detrimental; elevation of a low ineffective level may improve seizure control. A rise to a toxic level range requires reduction of the dose of primary drug or elimination of interfering drugs. Monitoring the blood levels of anti-epileptic drugs provides the best means to anticipate interactions and to regulate the doses when multiple medications have to be used.

Anti-Infective Agents↗

PubMed1975

Carbamazepine in difficult to control epileptic out-patients.

Twenty-three difficult to control patients with 1 or more seizures per week despite diphenylhydantoin (DPH), phenobarbital and/or primidone in near and toxic doses and blood levels were entered in the study. 3 had grand mal. 8 psychomotor seizures and 12 had both. During a 6 1/2 month study period the patient received active drug and placebo for 3 months each; randomized, double-blind. The dose was to be increased within 4 weeks up to 6 capsules per day equal to 1,200 mg of carbamazepine (C), while the doses or previously taken (basis) anticonvulsants were to remain unchanged. Hematopoetic system and heptic functions were monitored. Complete seizure control attributable to C was not achieved in any, but up to 50% improvement occurred in 12 patients. Questionable improvement was thought to take place in 3 patients, no change occurred in 7, and psychomotor seizures became more frequent in 1 patient. A clear-cut psychotropic effect was not observed. Adverse effects attributable to C were a decline of WBC below 4,000 with relative neutropenia in 3 patients followed by at return to the previous after discontinuation of C. Nystagmus and unsteadiness were seen in about half of the patients, and some headache and drowsiness occurred in one quarter. The highest C blood level was 11.8 mug/ml, the lowest 3.8 mug/ml (average 5.6 mug/ml) during 1,200 mg intake. It seemed, generally, that intoxication occurred with lower blood levels of carbamazepine in those patients whose basis anticonvulsant blood levels were highest.

Adolescent↗

PubMed1975

Methadone plasma levels in maintenance patients: the effect of dose omission.

The stability of methadone plasma levels during steady drug intake and the effects of a single dose omission on the methadone plasma level, were studied in 3 reliable patients (Group I) and in a nonselected group of 11 clinic patients (Group II). The plasma levels of methadone were determined by gas-liquid chromatography. In Group I patients receiving an average dose of 1.13 mg/kg (range 0.45-1.6 mg/kg) little day to day variation was seen: the average plasma level was 0.358 ug/ml with a variance of +/- 3.6% measured in 4 different days. Forty-eight hours after the last dose (after omission of a single dose), methadone plasma levels declined on the average by 0.179 ug/ml which represents a 50% decrease form the preomission average level. In Group II patients during the presumed steady methadone intake (average dose 1.25 mg/kg, range 0.57-1.75 mg/kg), the average plasma level of methadone was 0.377 ug/ml with a variance of 48.5% measured in 4 different days. A fall in methadone plasma levels occurred mainly after weekends in some of the Group II patients suggesting possibly nonconsumption of the prescribed dose of medication. The rapid and substantial decline of methadone plasma levels following a single dose omission is apparently a parallel to the observed rapid loss of methadone induced cross tolerance.

Chromatography, Gas↗

PubMed1975