Probable metabolic interaction between methadone and fluvoxamine in addict patients.

We report five cases where fluvoxamine (FLVX) was added to maintenance treatment with methadone (MTD) in addict patients with affective disorders. In view of the implication of FLVX in several metabolic drug interactions, MTD plasma levels were measured before and after treatment with FLVX. A slight increase (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In the remaining three patients, the interaction was more pronounced (40-100% increase of the MTD plasma level/dose ratio), with clinical manifestations of opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when starting or stopping treatment with FLVX in patients receiving maintenance treatment with methadone.

Compilation of selected public health laws: including particularly the Public health service act, the Clean air act, the Solid waste disposal act, the Mental retardation facilities and community mental health centers construction act, and the Narcotic addict rehabilitation act, the Federal food, drug, and cosmetic act, the Federal hazardous substances act, and the fair packaging and labeling act.

Prepared for the use of the Senate Committee on Labor and Public Welfare and the House Committee on Interstate and Foreign Commerce.

Decision-Making Deficits Linked to Real-life Social Dysfunction in Crack Cocaine-Dependent Individuals

Crack cocaine-dependent individuals (CCDI) present abnormalities in both social adjustment and decision making, but few studies have examined this association. This study investigated cognitive and social performance of 30 subjects (CCDI x controls); CCDI were abstinent for 2 weeks. We used the Social Adjustment Scale (SAS), Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT). Disadvantageous choices on the IGT were associated with higher levels of social dysfunction in CCDI, suggesting the ecological validity of the IGT. Social dysfunction and decision making may be linked to the same underlying prefrontal dysfunction, but the nature of this association should be further investigated. (Am J Addict 2010;00: 1-9).

Oral lesions in HIV infected individuals from Ribeirao Preto, Brazil

Objectives: The aim of this study was to diagnosis oral lesions related to HIV infection in individuals followed in the General Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. The presence of oral lesions was correlated with gender, age, smoking habit, levels of CD4 lymphocytes, HIV load, time of HIV seropositivity, AIDS condition, use of removable dental prosthesis, and use of HAART. Materials and Methods: 340 HIV infected individuals were selected for this study, all participants of the study were examined by only one practiced dentist which performed anamnesis, peribuccal and oral examination. Results: Oral lesions were observed in 113 of 340 (33.2%) HIV infected individuals. These oral lesions included: oral candidiasis (17.7%) of pseudomembranous (10.8%) and of erythematous types (6.9%), angular cheilitis (13.9%), hairy leukoplakia (11.8%), and oral ulcers (2.1%). Oral candidiasis lesions were more frequently observed in women (p. 033). Smoking addict participants presented a high frequency of tongue hairy leukoplakia (p. 038) and a reduced frequency of oral ulcers (p. 018). Hairy leukoplakia and pseudomembranous candidiasis were inversely correlated to CD4+ L levels and directly correlated with HIV load, behaving as immune depression markers. Hairy leukoplakia and pseudomembranous candidiasis also showed an inverse correlation with HAART use (p < .0001). Patients using mobile dental prosthesis presented a high frequency of erythematous candidiasis (p. 003). Conclusion: The inverse correlation with CD4+ L level and the direct correlation with HIV load suggest that oral lesions could be used as alternative clinical markers for poor immune condition in HIV infected individuals.

Sentido evolutivo do controle de constitucionalidade no Brasil

Consabido que para uma sociedade organizada se desenvolver política e juridicamente, indispensável se faz a existência de um documento formal, dotado de observância obrigatória, capaz de definir as competências públicas e delimitar os poderes do Estado, resguardando os direitos fundamentais de eventuais abusos dos entes políticos. Este documento é a Constituição, que, em todos os momentos da história, sempre se fez presente nos Estados, mas, inicialmente, não de forma escrita, o que fez com que surgisse, então, o constitucionalismo, movimento que defendia a necessidade de elaboração de constituições escritas, munidas de normatividade e supremacia em relação às demais espécies normativas, que visassem organizar a separação dos poderes estatais e declarar os direitos e as liberdades individuais. Porém, de nada adiantaria a edição de uma Lei Maior sem que houvesse mecanismos de defesa, no intuito de afastar qualquer ameaça à segurança jurídica e à estabilidade social, por conta de alguma lei ou ato normativo contrário aos preceitos estabelecidos na Constituição. O controle de constitucionalidade, pilar do Estado de Direito, consiste em verificar a compatibilidade entre uma lei ou qualquer ato normativo infraconstitucional e a Lei Excelsa e, em havendo contraste, a lei ou o ato viciado deverá ser expurgado do ordenamento jurídico, para que a unidade constitucional seja restabelecida. No Brasil, o controle de constitucionalidade foi instituído sob forte influência do modelo norte-americano e obteve diversos tratamentos ao longo das constituições brasileiras, porém, o sistema de fiscalização de constitucionalidade teve seu ápice com o advento da atual Constituição Federal, promulgada em 05.10.88, com a criação de instrumentos processuais inovadores destinados à verificação da constitucionalidade das leis e atos normativos. Além disso, a Carta da República de 1988, ao contrário das anteriores, fortaleceu a figura do Poder Judiciário no contexto político, conferindo, assim, maior autonomia aos magistrados na solução de casos de grande repercussão nacional, redundando em um protagonismo judicial atual. Nesse contexto, o Supremo Tribunal Federal, órgão de cúpula do Judiciário nacional e guardião da Constituição, tem se destacado no cenário nacional, em especial na defesa dos direitos e garantias fundamentais insculpidos na Lei Fundamental, fazendo-se necessária, desta forma, uma análise na jurisprudência da Corte, no sentido de verificar se, de fato, tem havido evolução no controle de constitucionalidade no Brasil ao longo dos últimos anos e, em caso afirmativo, em que circunstâncias isso tem se dado.

Ruptured pseudo-aneurysm of a femoral artery in a drug abuser revealed by post-mortem CT angiography.

A 35-year-old drug addict was found dead in a public toilet with a ruptured groin, which was later diagnosed to be a leaking pseudo-aneurysm. Investigation at the scene revealed impressive external hemorrhage related to a groin wound. Post-mortem computed tomography angiography demonstrated an aneurysm of the right femoral artery with leak of contrast liquid. Signs of blood loss were evident at autopsy, and histological examination revealed necrosis and rupture of the pseudo-aneurysm. Toxicological analyses were positive for methadone, cocaine, citalopram, and benzodiazepines. This is the first case report in the literature of a ruptured femoral pseudo-aneurysm with a post-mortem radiological diagnosis.

Influència dels tractaments mèdics i psicoterapèutics en la disminució del delicte en població addicta a drogues

En l'àmbit judicial es constata una relació entre drogoaddicció i delicte. Els addictes a drogues han iniciat amb freqüència algun programa de desintoxicació o han sol·licitat suport mèdic o psicològic. L'estudi es proposa avaluar l'associació entre la conducta il·legal i l'abús de substàncies tòxiques, així com interpretar l'eficàcia dels tractaments terapèutics en la disminució d’aquesta associació, i les repercussions de les teràpies tant sobre els pacients com sobre el seu entorn. És un estudi observacional prospectiu d’una mostra de 100 subjectes que tenen relació amb el consum de drogues d'abús, al Jutjat de Guàrdia de Barcelona i en subjectes interns del Centre Penitenciari de Joves de Barcelona. Els resultats de l’estudi diuen que el sexe masculí hi està representat en un 94%, la mitjana d’edat és de 25,5 anys, amb baix nivell d’estudis i sense professió qualificada. Gairebé la meitat de la mostra són estrangers i solters. Els pacients estudiats són politoxicòmans amb un consum majoritari de cocaïna (92%), cannabis (87%), alcohol (71%) i el 54% d’heroïna. Destaca l’alta freqüència dels UDVP i de la positivitat als tres virus (VIH, VHC, VHB), tot i que es demostra el descens de l’ús de la via parenteral. El 73% dels subjectes comenten delictes contra la propietat. El 93% de la mostra han estat en tractament, però en períodes curts (70%). El 72,7% que estan en PMM consumeixen habitualment cocaïna. Els pacients tractats amb psicofàrmacs són detinguts menys vegades que la resta de pacients. Pocs pacients han fet tractaments combinats amb psicoteràpia o lliure de drogues. Entre la població de detinguts, els tractaments rebuts han resultat beneficiosos pel que fa a autoestima, autoagressivitat, heteroagressivitat, conflictivitat penal i violència en els fets delictius, però aquestes variables quasi no es modifiquen en el cas dels joves. Els tractaments produeixen un benefici als pacients toxicòmans i disminueixen la conflictivitat penal. Els tractaments s’han d’iniciar en els primers estadis del consum, així com potenciar l’adhesió i el seguiment. Els centres penitenciaris de justícia juvenil, les comissaries i els jutjats de guàrdia són els llocs idonis per a l’abordatge del tractament del drogodependent.

Methadone maintenance treatment and St. John's Wort - a case report.

St. John's wort, a popular over-the-counter drug for treatment of depression, might reduce concentrations of drugs such as cyclosporin and indinavir and lead to drug resistance and treatment failure. No studies as yet have examined its influence on methadone plasma levels. The trough methadone plasma levels were measured in four patients (2 males, median age: 31 years; range 19 - 40 years) in methadone maintenance treatment just before the introduction of St. John's wort (900 mg/d) and after a median period of 31-day treatment (range 14 - 47). The study was proposed to addict patients about to start an antidepressant therapy. Introduction of St. John's wort resulted in a strong reduction of (R,S)-methadone concentration-to-dose ratios in the four median patients included, with a median decrease to 47 % of the original concentration (range: 19 % - 60 % of the original concentration). Two patients reported symptoms that suggested a withdrawal syndrome. Thus, prescription of St. John's wort might decrease methadone blood levels and induce withdrawal symptoms which, if not correctly identified and handled (by changing the antidepressant or by increasing the methadone dose), might cause unnecessary discomfort to the patient, lead to resumption of illicit drug uses, or be a risk factor for discontinuation of the methadone or antidepressant treatment.

Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir.

Abacavir and amprenavir, a nucleoside reverse transcription inhibitor and a protease inhibitor, respectively, are new drugs used for the treatment of HIV. Methadone blood concentrations were measured in five addict patients receiving methadone maintenance therapy before and after introduction of abacavir plus amprenavir. The administration of these two drugs for a median period of 14 days resulted in a significant reduction (P = 0.043) of methadone concentration, with a median decrease to 35% of the original concentration (range 28-87%). Two patients reported on several occasions nausea in the morning before the intake of the daily methadone dose, which is compatible with withdrawal reaction to opioids. Because amprenavir is a cytochrome P4503A4 substrate and is involved in the metabolism of methadone, reduction of methadone concentrations could be explained by an induction of cytochrome P4503A4.

Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers

Steady-state blood concentrations of (R)- methadone (i.e., the active form), (S)-methadone, and (R,S)-methadone were measured before and after introduction of paroxetine 20 mg/day during a mean period of 12 days in 10 addict patients in methadone maintenance treatment. Eight patients were genotyped as CYP2D6 homozygous extensive metabolizers (EMs) and two patients as poor metabolizers (PMs). Paroxetine significantly increased concentrations of both enantiomers of methadone in the whole group (mean increase for (R)-methadone +/- SD, 26 +/- 32%; range, -14% to +83%, p = 0.032; for (S)-methadone, 49 +/- 51%; range, -29% to +137%, p = 0.028; for (R,S)-methadone, 35 +/- 41%; range, -20% to +112%, p = 0.032) and in the group of eight EMs (mean increase, 32%, p = 0.036; 53%, p = 0.028; and 42%, p = 0.036, for (R)-methadone, (S)-methadone, and (R,S)-methadone, respectively). On the other hand, in the two PMs, (S)-methadone but not (R)-methadone concentrations were increased by paroxetine (mean increases of 36% and 3%, respectively). Paroxetine is a strong CYP2D6 inhibitor, and these results confirm previous studies showing an involvement of CYP2D6 in methadone metabolism with a stereoselectivity toward the (R)-enantiomer. Because paroxetine is a mild inhibitor of CYP1A2, CYP2C9, CYP2C19, and CYP3A4, increase of (S)-methadone concentrations in both EMs and PMs could be mediated by inhibition of any of these isozymes.

El rol del paciente experto en el tratamiento de las adicciones: una propuesta para paliar las altas tasas de abandono prematuro en comunidades terapéuticas

El objetivo de este estudio recae en cómo y de qué forma el ex adicto a sustancias alteradoras del ánimo (E-ASAA), cursando por el estadio de mantenimiento, puede ejercer el rol de asesor y promotor de salud, como “Paciente Experto”, conjuntamente con los profesionales especializados en drogodependencias. Paralelamente este “cómo y de qué forma” viene a dar respuesta a una necesidad existente en las Comunidades Terapéuticas, a saber, reducir las Altas Voluntarias (AV) de los residentes recién incorporados y tras su Alta Terapéutica (AT). Sin embargo, se requiere de una investigación de tipo cualitativo para determinar los factores desencadenantes que inducen a esta prevalencia de AV y recaídas post-AT. Los resultados extraídos de la investigación a informantes clave muestran como existe un deficitario asesoramiento pre-entrada y acompañamiento post-AT. El E-ASAA, debidamente formado, podría dar respuesta a estas demandas asistenciales, mejorando así la completa reinserción de los usuarios de CCTT. La Propuesta del Proyecto “Mi amigo de Comunidad” integra este conocimiento aportando soluciones.

Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment

Methadone is a 50:50 mixture of two enantiomers and (R)-methadone accounts for the majority of its opioid effect. The aim of this study was to determine whether a blood concentration of (R)-methadone can be associated with therapeutic response in addict patients in methadone maintenance treatment. Trough plasma concentrations of (R)-, (S)- and (R,S)-methadone were measured in 180 patients in maintenance treatment. Therapeutic response was defined by the absence of illicit opiate or cocaine in urine samples collected during a 2-month period prior to blood sampling. A large interindividual variability of (R)-methadone concentration-to-dose-to-weight ratios was found (mean, S.D., median, range: 112, 54, 100, 19-316 ng x kg/ml x mg). With regard to the consumption of illicit opiate (but not of cocaine), a therapeutic response was associated with (R)- (at 250 ng/ml) and (R,S)-methadone (at 400 ng/ml) but not with (S)-methadone concentrations. A higher specificity was calculated for (R)- than for (R,S)-methadone, as the number of non-responders above this threshold divided by the total number of non-responders was higher for (R,S)-methadone (19%) than for (R)-methadone (7%). The results support the use of therapeutic drug monitoring of (R)-methadone in cases of continued intake of illicit opiates. Due to the variability of methadone concentration-to-dose-to-weight ratios, theoretical doses of racemic methadone could be as small as 55 mg/day and as large as 921 mg/day to produce a plasma (R)-methadone concentration of 250 ng/ml in a 70-kg patient. This demonstrates the importance of individualizing methadone treatment.