Comparison of patterns of drug levels in head and body hair for medico-legal and workplace testing.

This paper presents concentration ranges and positivity rates for the common drugs, alcohol markers, new psychoactive substances (NPS) and anabolic steroids tested in head hair (n = 138,352) and body hair (n = 9532) on samples of hair from medico-legal (n = 112,033) and workplace (n = 35,851) sectors tested in our laboratory. Statistically significant higher levels were found more often in the various types of body hair when compared with head hair, but fewer cases exhibited lower levels. For example, statistically significant higher levels were detected in leg hair for cannabinol, THC, methadone and EtG and in beard hair for THC, THC-COOH and 6-acetylmorphine. In contrast, significantly lower levels were detected in axilla hair for cannabinol, THC and for EDDP, but median levels of mephedrone and DHEA were higher. Overall, higher medium levels were detected in head hair samples tested in the UK when compared with those previously published for samples tested in Germany, indicating geographical differences in drug consumption. Recommendations are, firstly, that hair testing laboratories use the results of their own compiled previous positive results for guidance when interpreting hair testing results and, secondly, that laboratories periodically share and combine their accumulated data with other testing laboratories. The latter could be used to establish reference ranges associated with specific technical procedures which would improve interlaboratory comparability and improve laboratory testing services when interpreting hair testing results.

Testing venous carbohydrate-deficient transferrin or capillary phosphatidylethanol with concurrent ethyl glucuronide and ethyl palmitate hair tests to assess historical and recent alcohol use.

Hair biomarkers, ethyl glucuronide (EtG) and ethyl palmitate (EtPa), together with blood biomarker tests, carbohydrate-deficient transferrin (CDT) or phosphatidylethanol (PEth), are commonly used in identifying patterns of alcohol consumption as they possess different windows of detection. The detection of EtG in hair samples is mainly used in combination with EtPa when hair cosmetic treatments such as hair colouring and bleaching affect EtG levels. The main purpose of our study was to investigate the differences in frequency distribution of positive CDT and PEth results indicating alcohol had been used, when EtG and EtPa were not detected, where evidence of abstinence is paramount. Of the total 602 cases, for 179 (29.7%), neither EtG nor EtPa markers were detected. Of these, 0.5% of the cases produced positive CDT. However, 18.6% produced positive PEth, a significantly higher proportion. A similar pattern emerges when results are evaluated according to whether hair had been either cosmetically treated or untreated. When hair was untreated, one case produced positive CDT, and 19.3% were positive for PEth (median of 51 ng/ml). No cases of positive CDT results, but 20.8% of PEth were positive (median of 106.5 ng/ml) when hair samples had been cosmetically treated. Whether EtG or EtPa markers were detected or not, significantly higher proportions of PEth than CDT were seen. The results of this study substantiate the case for using hair EtG in conjunction with a PEth test, rather than CDT test, for efficient monitoring of recent and historical alcohol consumption.

The Effect of Prolonged Storage Time on the Stability of Fatty Acid Ethyl Esters in Hair Samples.

The advantages of analysis of drugs in hair samples are recognized for the long window of detection, alongside easy sampling and long stability after sample collection. Alcohol markers, ethyl glucuronide (EtG) and total fatty acid ethyl esters (FAEEs) in hair, are widely used for monitoring alcohol consumption for clinical and forensic purposes. Although stability of drugs and EtG in hair samples is documented to a certain extent, stability of FAEEs in hair samples after collection has not been reported. This study covered hair samples that had been tested for FAEEs on the day of arrival at the laboratory and retested between 4 and 80 months later. The statistical analysis of the data set reveals significant lower FAEEs levels including ethyl palmitate (EtPa) ester levels when samples were retested for the second time after 6 days of storage under ideal conditions. Specifically, the results suggest that when measuring total FAEEs or solely EtPa in hair samples, the elapsed time between sample collection and analysis of the sample needs to be considered when interpreting the results. The recommendation is that whenever hair samples need to be tested for total FAEEs or EtPa, the analytical procedure needs to be performed within 1 week after collection in order to obtain meaningful results. The study results substantiate the case for the use of hair samples solely for the analysis of EtG, in conjunction with other measurements such as full blood count, carbohydrate-deficient transferrin test, liver function test or phosphatidylethanol alongside clinical assessment for a more effective evaluation of alcohol consumption.

Adulterants in crack cocaine in Brazil.

INTRODUCTION: Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. METHOD: We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. RESULTS: Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). CONCLUSION: Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Adulterants in crack cocaine in Brazil / Adulterantes no crack vendido na "Cracolândia"

Abstract Introduction Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence. Method We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained. Results Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%). Conclusion Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Resumo Introdução O Brasil é o maior consumidor mundial de crack, e a dependência é um grande problema de saúde pública. Este é o primeiro estudo a investigar a prevalência de adulterantes potencialmente nocivos presentes em amostras de cabelo de pacientes brasileiros com dependência de crack. Métodos Foram avaliados adulterantes em amostras de cabelos extraídos por conveniência de 100 pacientes internados na unidade de observação de 48 horas do Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), o maior centro de tratamento de dependência do Brasil. Uma análise transversal foi realizada com os dados obtidos. Resultados Foram encontrados adulterantes em 97% das amostras de cabelo analisadas. O adulterante mais prevalente foi a lidocaína (92%), seguida da fenacetina (69%) e levamisol (31%). Conclusão Os adulterantes foram amplamente prevalentes em amostras de cabelo de usuários de crack tratados no CRATOD: pelo menos um adulterante estava presente em praticamente todas as amostras de cabelo coletadas. Isso aponta para a necessidade de monitorar os efeitos adversos no ambiente clínico, a fim de proporcionar a esse grupo de pacientes de alto risco cuidados imediatos e efetivos relacionados às complicações agudas e crônicas associadas a esses adulterantes.

Data on ethyl glucuronide and cocaethylene concentrations in the hair of cocaine users.

We present data on ethyl glucuronide and cocaethylene concentrations from the hair of cocaine users. Head hair from 64 subjects, previously tested for cocaine, cocaethylene, benzoylecogonine and anhydroecgonine methyl ester (AEME), were subsequently analysed for Ethyl Glucuronide (EtG). Samples were prepared by solid phase extraction and analysed using gas chromatrography coupled to tandem mass spectrometry. The dataset is made available to allow analysis of possible correlation between cocaethylene and ethyl glucuronide or between other metabolites presented in the data.

Hair analysis when external contamination is in question: A review of practical approach for the interpretation of results.

Despite having been extensively discussed over the last decade, the differentiation between systemic exposure and external contamination still continues to be one of the limitations of hair testing for drugs. For this reason, we consider it worthwhile to re-state some basic principles in this short review. Various studies investigating a diversity of wash protocols, most using artificially contaminated hair with cocaine, have been valuable in evaluating wash efficacy and in understanding the incorporation of drugs in hair. However, assessments of wash efficacy made with real hair samples, as opposed to artificially contaminated samples, provide a different perspective, and demonstrate how rarely external contamination affects the interpretation of results. Data from a large number of hair samples from crack cocaine users, confirmed the usefulness of our protocol to remove most of the externally deposited cocaine. The data showed that hair levels of cocaine and benzoylecgonine in crack cocaine users were overall high with ratio of benzoylecgonine to cocaine in all samples above 0.1. The wash residue concentrations of cocaine ranged from not detected to 21ng/mg with a median of 0.5ng/mg. Cocaine was detected in the wash residue in 105 out of 138 samples. The wash to hair cocaine ratio ranged from not detected to 0.36 with a median of 0.02. The wash to hair cocaine ratios were below 0.07 in 133 cases. The five cases that produced wash to hair ratios above 0.1, one sample was at 0.11, three at 0.13 and one at 0.36, possibly because these cases were at the lower end of cocaine levels, however, we could not rule out that the hair was contaminated. Whilst it is not possible to differentiate between the drug extracted from the hair and the drug attached to the outside of the hair, we can compare levels of drug in the wash residue with levels detected in the hair sample. In addition, further diagnostic criteria must be applied to minimise potential misdiagnosis of external contamination. When drugs are detected in hair, individuals have clearly been in an environment where drugs are present, but it is only on rare occasions that it is unclear whether this is the result of drug use or of external contamination, and, in those cases, the results of testing need to be interpreted in the light of corroborating evidence from clinical data or social context.

Commentary on current changes of the SoHT 2016 consensus on alcohol markers in hair and further background information.

The consensus on alcohol markers in hair was revised for the fourth time by an expert group of the Society of Hair Testing based on current state of research. This revision was adopted by the members of the Society during the business meeting in Brisbane on August 29th 2016. For both markers, ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), two cut-off values for discrimination between teetotalers or occasional low amount consumption and moderate alcohol drinking (low cut-off), and between non-excessive (abstinence up to moderate alcohol intake) and chronic excessive drinking (high cut-off value) were critically examined. For the current revision, the cut-off values for EtG (7pg/mg and 30pg/mg, respectively) remained unchanged despite different findings or discussions published in the meantime. This was mainly due to the lack of broader data collections from new studies with great numbers of volunteers following thorough study concepts. In contrast, an essential change of the consensus was accepted for the FAEEs, where the concentration of ethyl palmitate (E16:0) can be used autonomously for interpretation instead of the concentration sum (ΣFAEE) of the four esters ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate, as previously applied. After evaluation of the data from seven laboratories, the E16:0 cut-off for abstinence assessment was defined at 0.12ng/mg for the 0-3cm segment and at 0.15ng/mg for the 0-6cm segment. The cut-off for chronic excessive drinking was fixed at 0.35ng/mg for the 0-3cm segment and at 0.45ng/mg for the 0-6cm segment. The use of E16:0 with these cut-offs in place of ΣFAEE for alcohol intake assessment produces only a minor loss in discrimination power, leads to no essential difference in the interpretation concerning chronic excessive alcohol consumption and is suitable to confirm EtG results in abstinence assessment if ethanol containing hair sprays or lotions are excluded.

Differentiation between consumption and external contamination when testing for cocaine and cannabis in hair samples.

It is possible for hair to be externally contaminated by drugs like cannabis or cocaine, which are smoked or snorted. Three steps are commonly employed to minimize the chance of external contamination causing misinterpretation of the results of a hair test. The first consists of decontamination of hair samples by washing the hair before analysis, the second is the use of cut-off levels, and the third is the detection of both the parent drugs and appropriate levels of their metabolite(s) in the hair sample. We propose an additional step for the assessment of drug use using hair samples combined with decontamination data. Hair samples from 186 drug users were analyzed along with their wash residues by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results of the hair analysis of the 140 samples for cocaine showed that 85.5% (N=89) of the samples passed 'cocaine use' criteria for metabolites ratios and 12.5% (N=13) for wash residue criteria (<10% of cocaine in the wash residue) leading to conclusive interpretation. Only two cases (1.9%) had an uncertain conclusion of drug consumption because cocaine levels in the wash residue were >10% of the levels in the hair. The results of the cannabis set of samples (N=46) were not as clear-cut, as a comparatively large number of samples (15.2%) had relatively high levels of THC in the wash residues. To use this approach, it is important that laboratories testing drugs in hair samples can demonstrate that the method utilized does not generate significant levels of the cocaine metabolites.

Workplace drug testing, different matrices different objectives.

Drug testing is used by employers to detect drug use by employees or job candidates. It can identify recent use of alcohol, prescription drugs, and illicit drugs as a screening tool for potential health and safety and performance issues. Urine is the most commonly used sample for illicit drugs. It detects the use of a drug within the last few days and as such is evidence of recent use; but a positive test does not necessarily mean that the individual was impaired at the time of the test. Abstention from use for three days will often produce a negative test result. Analysis of hair provides a much longer window of detection, typically 1 to 3 months. Hence the likelihood of a falsely negative test using hair is very much less than with a urine test. Conversely, a negative hair test is a substantially stronger indicator of a non-drug user than a negative urine test. Oral fluid (saliva) is also easy to collect. Drugs remain in oral fluid for a similar time as in blood. The method is a good way of detecting current use and is more likely to reflect current impairment. It offers promise as a test in post-accident, for cause, and on-duty situations. Studies have shown that within the same industrial settings, hair testing can detect twice as many drug users as urine testing.

Differentiation between drug use and environmental contamination when testing for drugs in hair.

The differentiation between systemic exposure and external contamination for certain drug groups has been frequently referred to as one of the limitations of in drug testing in hair. When hair samples are used, three steps are usually employed in order to minimise the possibility of external contamination causing a misinterpretation. The first consists of decontaminating hair samples by washing the hair before analysis, the second is the detection of the relevant metabolites in the hair samples and the third is the use of cut-off levels. Difficulty in the interpretation arises when metabolites are not detected either due to external contamination of the hair or low doses of the drugs used. A wash protocol needs to be practical and ideally remove any drug deposited on the external portion of the hair. We propose an additional step that helps considerably in the interpretation of the results with the aim to establish a consensus: the analysis of the wash residue (W) and its comparison with the levels detected in hair (H). The wash residue is the remainder of a quick wash with methanol which is dried and reconstituted in buffer before analysis. The detection of small quantities of analytes that are not susceptible to external contamination in the wash residue, such as metabolites or drugs such as dihydrocodeine, indicates that the washing procedure is in fact able to remove drugs from the hair shaft. Where the W/H ratio is less then 0.1 or null, it would tend to indicate drug use as opposed to environmental contamination. Where the W/H ratio is above 0.1 but less than 0.5, it is likely to indicate possible use possibly combined with a level of external contamination. A W/H ratio greater than 0.5 is likely to indicate that the source of most of the drug in the wash residue is from external contamination. In this last case, the source of levels detected in the hair is questionable, as it is not possible to be absolutely sure that all external contamination was removed, and so use cannot be confirmed. Two hundred and sixteen hair samples from a population where external contamination could be expected (Police Investigations on drug related cases) and their wash residue were analysed. The W/H ratios of 891 results were evaluated over 13 analytes. Between 74 and 100% of the analytes studied produced W/H ratios less than 0.5, in particular in cannabis (93%) and cocaine (95%), where external contamination is more likely because of the way the drug is used. The data do show that while it is very important to always be aware of alternative explanations for test results, the likelihood of external contamination confounding the interpretation of hair tests can be reduced to manageable proportions.

Do drug users use less alcohol than non-drug users? A comparison of ethyl glucuronide concentrations in hair between the two groups in medico-legal cases.

Two groups were selected from the remainder of hair samples that had been tested for drugs at TrichoTech for medico-legal cases: samples that tested negative (drug-negative group; N=42, age 33.4+/-7.2 years) and samples that tested positive for drugs (drug-positive group; N=57, age 32.5+/-8.8 years). A rapid, simple method to detect the ethanol metabolite, ethyl glucuronide (EtG) in hair has been developed. The hair samples were sectioned, and then submitted to overnight sonication in water. Samples then underwent SPE using anion exchange cartridges, followed by derivatisation with N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA), before confirmation by GC-MS/MS. The assay produced excellent linearity and sensitivity over the calibration range 0.02-1.0 ng/mg, assuming a 10 mg hair sample. The mean age of the two groups was not statistically different (p=0.575, Student t-test), indicating a homogeneous group. Twelve of the 57 (21.0%) hair samples of the drug-positive group tested positive for EtG, and 17 of the 42 (40.5%) hair samples of the drug-negative group tested positive for EtG. The mean concentration of EtG in the drug-positive group was 0.011 ng/mg compared to 0.107 ng/mg in the drug-negative group. When the full results of this study were subjected to statistical analysis it was shown that EtG levels in the drug-negative group were statistically higher than those found in the drug-positive group (p<0.05). This preliminary finding may be of use in the study of addiction and adds valuable data to previous studies regarding the use of EtG as a valuable marker for alcohol levels in hair.

Prevalence and disposition of drugs of abuse and opioid treatment drugs in oral fluid.

Testing oral fluid for drugs of abuse has been studied under many conditions but rarely has been evaluated in large population databases. We evaluated oral fluid tests in a database from a commercial laboratory in the United Kingdom composed of 8679 confirmed positive results. The results originated from 635,000 specimens collected over the period of May 2004 through September 2006. Oral fluid specimens were collected with the Intercept oral fluid collection device, screened by enzyme immunoassay, and confirmed by GC-MS or GC-MS-MS. The database was organized by collection settings (legal/treatment, N = 8198 specimens; and workplace, N = 481 specimens) and by drug groups (without consideration of collection setting). The drug groups were as follows (number of confirmed positives): amphetamines (468); benzodiazepines (892); buprenorphine (276); cannabinoids (725); cocaine (1443); methadone (998); and opiates (5739). The goal of the study was to provide drug/metabolite prevalence data, concentrations, and drugs/metabolite patterns encountered in oral fluid. Comparison of results by collection setting indicated differences in relative frequency, primarily for opiates and cannabinoids. Opiate positives were most frequently observed for specimens collected in legal/treatment settings, whereas cannabinoids were most frequently reported in the workplace. An array of information on drug and metabolite occurrences and concentration arose from evaluation of the data by drug groups. Amphetamine was the predominant drug reported for the Amphetamines Group; approximately 10% were also positive for MDA and/or MDMA; and methamphetamine was rarely reported. Multiple combinations of diazepam, nordiazepam, oxazepam, temazepam, chlordiazepoxide, and lorazepam were reported for the Benzodiazepine Group. Buprenorphine, an opioid treatment drug, was the predominant analyte reported, but low concentrations of norbuprenorphine were frequently reported. THC was the predominant analyte reported in the Cannabinoids Group and was frequently reported in combination with cannabidiol and cannabinol. THCCOOH was reported in only 10.8% of these specimens and was never reported in the absence of THC. HO-THC was reported in 5.7% of the specimens. In the Cocaine Group, cocaine was present, often in combination with BZE, but also as the sole analyte in 17.3% of the specimens. AEME and cocaethylene were reported in 10.4% and 5.5% of the specimens. Methadone, another opioid treatment drug, was reported in all specimens for the Methadone Group; EDDP was reported in 30.1% of the specimens. In the Opiates Group, morphine, codeine and 6-acetylmorhine were most frequently reported, often in combination. The frequency of detection of 6-acetylmorphine when morphine was present (N = 4575 specimens) was 77.5%. Surprisingly, heroin (19.0%; N = 1091 specimens) and 6-acetylcodeine (24.9%; N = 1431 specimens) were frequently reported. The results from analysis of this large oral fluid database offer a rich mixture of new information on detection frequency, drug and metabolite patterns, and concentration data on drugs of abuse.

Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample.

This paper presents an overview of the most common sectioning patterns utilised in the analysis of hair for drug use; report on the major user groups (sectors) that currently make use of hair analysis in the United Kingdom (UK); present the results for the different drug groups analysed in samples of hair samples analysed at TrichoTech between 2001 and 2005. A total of 186,084 tests on 34,626 hair samples were performed for the commonly requested drug groups. There were 145,799 enzyme-linked Immunosorbent positive screening tests (ELISA), which were subsequently confirmed by gas chromatography equipped with mass spectrometry detection (GC-MS). The two major sectors were the Medico-Legal sector (65%) and Workplace (20%). Police (Forensics), Clinical Monitoring, Schools, Research and Insurance accounted together for the remaining 15% of the samples. Combinations of several sections patterns were requested covering periods from the most recent month up to 24 months. The most common sectioning pattern was one single section measuring 3 cm, to cover the most recent 3 months (44%), which in some cases was complemented by a further 3 cm to cover together 6 months (13%). The second most common sectioning pattern was the analysis of three sections of 1cm each to cover the most recent 3 months (28%), when a more detailed evaluation of drug use pattern was relevant. Samples collected from other areas of the body such as axilla, pubic, chest, beard and leg, constituted 6% of the samples. The analysis of monthly sections plays an important role in the evaluation and interpretation of drug use, particularly in certain Medico-Legal cases. The sectors with the highest rates of positive results were Police (Forensics) (78%), Medico-Legal (62%) and Clinical (54%). The common drugs in each group were cannabinol (27%), cocaine (25%), morphine (17%), amphetamine (13%) and diazepam (15%). The positive rate for the Workplace sector was 10%. The most common drugs detected in the Workplace samples in each group were: THC (4%), codeine (2%), cocaine (2%), MDMA (0.5%) and diazepam (0.1%). The concentration levels of drugs found in samples from the workplace were lower than in the other sectors (95% of cases). The exceptions were for dihydrocodeine and MDMA, where levels were 170 and 143% higher, respectively. However, the maximum levels detected in the Workplace samples were lower. The Medico-Legal sector is the most prevalent sector using hair analysis in the UK but the rate of Workplace sector use of hair testing is increasing. One in 10 workplace hair tests detected the presence of at least one drug, which is twice the rate of detection using urine, which is a 1 in 20 urine sample. This means that the chances of identifying people on drugs in the workplace by testing hair samples are twice as likely than urine samples.

GC-MS-MS determination of gamma-hydroxybutyrate in blood and urine.

A gas chromatographic-tandem mass spectrometric (GC-MS-MS) method for determining trace concentrations of gamma-hydroxybutyrate (GHB) in blood and urine has been developed. Multiple reaction monitoring was used to detect parent and daughter ions of GHB, 233 and 147, respectively, following liquid-liquid extraction with acetonitrile and derivatisation with N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA). Deuterated GHB was used as an internal standard. The assay produced excellent linearity and sensitivity without conversion to gamma butyrolactone. The lower limit of quantitation (LLOQ) in 50 microL of sample was 2.5 microg/mL. The expanded uncertainty values for intra- and interassay results were +/- 0.097 and +/- 0.123 ng/mL at a confidence level of 95% for blood and urine, respectively. Endogenous concentrations of GHB were found to be in the range of 0.3 to 6 microg/mL in urine and 0.5 to 2.3 microg/mL in blood, confirming previously suggested cut-off values for forensic analysis.

Cognitive Functions of epileptic patients on monotherapy with phenobarbitone and healthy controls

Estudos quantitativos anteriores têm demonstrado que hereditariedade, dano cerebral, aspectos psico-sociais, fenômenos ictais e interictais e drogas antiepilépticas interferem na disfunçäo cognitiva de pacientes epilépticos. Neste estudo os métodos objetivos incluiram memória e reconhecimento imediatos e tardio nas figuras, teste de Stroop e seleçäo auditiva. Vinte pacientes com epilepsia localizada sintomática entre 17 e 52 anos de idade (27 ñ 10, média ñ d.p.) foram comparados a grupo controlado para idade e classe social. Os pacientes tinham concentraçöes terapêuticas (25 ñ 12 µg/ml) de fenobarbital e epilepsia ativa com 1,94 crises generalizadas tônico-clônicas, 0,85 parciais simples e 6,28 parciais complexas por mês (médias). Pacientes tiveram performances piores que controles em todos testes (p < 0.05 a 0.001), indicando disfunçäo cognitiva generalizada relacionada com crises epilépticas e/ou tratamento com barbitúricos. Sugerimos que outros estudos com populaçöes uniformes em regimes monoterapêuticso e síndromes epilépticas uniformes sejam realizados, para isolar fatores relacionados à disfunçäo cognitiva de apcientes epilépticos

Doses-carga de carbamazepina e difenil-hidantoína: utilizaçäo em pacientes de alto risco / Carbamazepine and phenytoin loading-doses: utilization in high-risk patients

Doses-carga de difenil-hidantoína (1000mg) e carbamazepina (600mg) foram administradas oralmente a respectivamente 10 e 6 pacientes com crises epilépticas secundárias a doença aguda neurológica ou síndrome de abstinência alcoólica. No grupo da difenil-hidantoína a idade variou de 12 a 73 anos e as concentraçöes séricas 2, 4, 6, 8, 12 e 18 horas após a administraçäo foram 7,6, 8,8 8,7, 7,2 e 6,5 micrograma/ml (média). Näo foram anotados efeitos colaterais importantes por um método quantitativo. No grupo da carbamazepina a idade variou de 25 a 56 anos e as concentraçöes séricas nas mesmas horas foram 3,9, 5,3 6,5, 7,5 7,4 e 8,2 micrograma/ml. Efeitos colaterais foram discretos. Näo foi necessária medicaçäo suplementar durante as 24 horas após a administraçäo das doses-carga. Embora ambos os esquemas tenham controlado a situaçäo clínica sem efeitos colaterais relevantes, as concentraçöes séricas foram sub-terapêuticas no caso da difenil-hidantoína. Sugerimos que a dose-carga ideal de difenil-hidantoína é 1500mg. A dose-carga de carbamazepina foi eficaz e produziu níveis séricos terapêuticos. A estabilidade dos níveis séricos durante o período de estudo torna este esquema útil no controle subagudo de crises epilépticas frequentes, no tratamento de manutençäo de estado de mal epiléptico e na síndrome de retirada alcoólica