Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

Bilateral ocular deposit of chlorpromazine / Depósito ocular bilateral de clorpromazina

ABSTRACT Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern in the lens. The total amount exceeds 2.000g (significant for the ocular alterations described) considering the patient's daily dosage of chlorpromazine of 300mg for ten years. After performing complete ophthalmic evaluation and discarding other causes for the ocular deposits, we diagnosed a secondary corneal deposit and cataract due to the use of chlorpromazine. This case reinforces the importance of periodic follow-up with an ophthalmologist for chlorpromazine users to trace ocular changes, heeding the exposure time and its dosage.

RESUMO A clorpromazina é uma medicação muito empregada na psiquiatria para tratamento de psicoses, especialmente em casos de esquizofrenia. Desde 1964 existem artigos publicados que correlacionam o uso dessa medicação com o aparecimento de alterações oculares. Neste trabalho, relatamos o caso de um paciente de 65 anos com efeitos oculares devido à terapia de longo prazo com clorpromazina. A biomicroscopia de ambos os olhos apresentou depósitos granulares difusos e de cor marrom, mais proeminente ao nível do estroma profundo e do endotélio da córnea, além de depósitos castanhos subcapsulares anteriores centrais em um padrão estrelado no cristalino. Considerando a dose diária de clorpromazina de 300mg por 10 anos usada pelo paciente, a quantidade total ultrapassa 2.000g (dose considerada significativa para as alterações oculares descritas). Após avaliação oftalmológica completa e descartado outras causas desses depósitos oculares, foram diagnosticados depósito corneano e catarata secundários ao uso de clorpromazina. O caso apresentado reforça a importância do acompanhamento oftalmolÓgico periÓdico de usuários de clorpromazina para o rastreio de alteraçÕes oculares, atentando-se ao tempo de exposição à droga e à posologia da mesma.

Combined influence of illness duration and medication type on visual sensitivity in schizophrenia

Objective: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. Methods: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. Results: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. Conclusion: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.

Lesão hepática grave induzida por fármacos anticonvulsivantes: relato de casos / Serious liver injury induced by anticonvulsants drugs: case reports

JUSTIFICATIVA E OBJETIVOS: Inúmeros medicamentos empregados rotineiramente na prática médica podem apresentar como efeito adverso significativo a agressão hepática, manifestando-se, por vezes, com lesões graves irreversíveis, sendo possível causa de óbito em determinadas situações. O objetivo deste estudo foi relatar dois casos de pacientes que apresentaram hepatotoxicidade por fármacos anticonvulsivantes, suas consequências e possível prevenção. RELATO DOS CASOS: Caso 1: Paciente do sexo feminino, 12 anos, com história de epilepsia, em uso de carbamazepina (CBZ), haloperidol, clorpromazina e clobazan. Ao exame clínico apresentava-se sonolenta e confusa, com exames laboratoriais contendo dosagem de CBZ elevada e enzimas hepáticas alteradas. Apresentou piora progressiva com surgimento de icterícia, elevação de enzimas hepáticas e diminuição do nível de consciência. A paciente evoluiu com broncopneumonia, hemorragia pulmonar, insuficiência respiratória e óbito. Caso 2: Paciente do sexo masculino, 4 anos, em uso contínuo de depakene, foi encaminhado com quadro de sonolência, icterícia, diminuição do nível de consciência, náuseas e dor abdominal. Houve agravamento do quadro hemodinâmico, com abalos mioclônicos, choque hipovolêmico e óbito. Durante a internação apresentou elevação de enzimas hepáticas e, assim como no primeiro caso, as sorologias virais eram negativas e a tomografia de crânio não apresentava anormalidades. CONCLUSÃO: Nos últimos anos, lesões hepáticas induzidas por diferentes agentes têm sido cada vez mais observadas. E, progressivamente, a importância dada a esse fenômeno tem aumentado de maneira significativa. Sendo o fígado o principal órgão metabolizador corporal, é esperado um comprometimento proporcionalmente extenso à medida que um número crescente de substâncias farmacológicas é utilizado. Diante do exposto, destaca-se a importância do uso racional de interações medicamentosas, na tentativa de prevenir lesões possivelmente evitáveis.

BACKGROUND AND OBJECTIVES: Countless medicines employees routinely in medical practice can present as significant adverse effect the hepatic aggression, manifesting, sometimes, with serious irreversible injuries, being a possible cause of death in determined situations. The objective of this study was reported two cases of patients who presented hepatotoxicity by anticonvulsants, its consequences and possible prevention. CASE REPORTS: Case 1: Female patient, 12 years, with a history of epilepsy, in use of carbamazepine (CBZ), haloperidol, chlorpromazine and clobazam. On clinical examination the patient was drowsy and confused, with laboratory containing elevation of CBZ dosage and liver enzymes changed. There was progressive worsening, with appearance of jaundice, elevation of liver enzymes and decreased level of consciousness. The patient evolved with bronchopneumonia, pulmonary hemorrhage, respiratory failure and death.Case 2: Male patient, 4 years, in continuous use of depakene, was directed with drowsiness, jaundice, decreased level of consciousness, nausea and abdominal pain. There was aggravation of hemodynamic status, with myoclonic tremors, hypovolemic shock and death. During hospitalization in our department, presented liver enzymes elevated and, as in the first case, viral serology was negative and tomography of skull showed no abnormalities. CONCLUSION: In recent years, liver injury induced by different agents has been increasingly observed. And gradually, the importance given to this phenomenon has increased significantly. Being the liver the main metabolizing organ body is expected a proportionally extensive involvement as a growing number of pharmacological substances is used. Given the above, highlights the importance of rational use of drug interactions in an attempt to prevent possibly avoidable injuries.

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period / Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anos

OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females), with mean year age of 34.8 (range 21-57), suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38), and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg), chlorpromazine (n=105, 100-400 mg) or clozapine (n=115, 75-600 mg). The scores of psychometric instruments (GWB, PANSS, CGI) were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( ÷2=315.7, df=34, p<0.001). Clozapine was safer and had fewer adverse effects (average of 0.9 adverse events per patient) than haloperidol (2.7) and chlorpromazine (3.2). CONCLUSIONS: Clozapine, in low doses of flexible regime, in long term (five years) showed better effectiveness in chronic schizophrenics with positive and negative symptoms than typical antipsychotics.

OBJETIVO: O propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. MÉTODO: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57). Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38) e os surtos subsequentes apareceram em média 4,1±0,5 anos após. Os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg), clorpromazina (105 pacientes com dose entre 100 e 400 mg) e clozapina (115 pacientes com dose entre 75 e 600 mg). Os instrumentos psicométricos utilizados (GWB, PANSS e CGI) foram regularmente empregados durante os 5 anos do estudo. RESULTADOS: Os 66 pacientes respondedores ao tratamento foram incluídos no protocolo de análise: 12, 10 e 16 apresentavam síndrome esquizofrênica positiva e 7, 6 e 15 síndrome negativa esquizofrênica com haloperidol, clorpromazina e clozapina, respectivamente. Diferenças estatísticas significantes foram observadas em todas as avaliações psicométricas em ambas síndromes esquizofrênicas favorecendo a clozapina. A distribuição de 18 tipos de efeitos colaterais observados foi diferente de modo significativo entre os 3 grupos estudados. A clozapina foi a droga que apresentou menos efeitos colaterais. CONCLUSÃO: A clozapina administrada por longo termo em pequenas doses em regime flexível apresenta melhor eficácia nas síndromes esquizofrênicas quando comparada a outras drogas antipsicóticas.

Probable Case of Neuroleptic Malignant Syndrome Following Administration of Antituberculotic Drugs in a Chlorpromazine-Treated Patient

Neuroleptic malignant syndrome (NMS), a potentially fatal adverse reaction to neuroleptics, is known to occur more often in the initial stage of antipsychotic treatment. We describe a patient with chronic schizophrenia who, in a few days after the addition of antituberculotic drugs to his antipsychotic regimen, developed probable NMS without pyrexia. We reasoned that rifampin, a strong hepatic enzyme inducer, decreased the plasma chlorpromazine concentration of the patient, with the result of cholinergic hyperactivity and finally, the symptoms of NMS. Therefore, physicians should be aware of drug interactions and the likelihood of NMS, and consider antipsychotic dose adjustment when prescribing drugs that may influence pharmacokinetic properties of antipsychotics in a patient with schizophrenia receiving long-term antipsychotic treatment.

Protective effect of melatonin against chlorpromazine-induced liver disease in rats

To evaluate the possible protective effect of orally administered melatonin against Chlorpromazine [CPZ]-induced liver disease in rats. We performed this study in the College of Pharmacy, University of Baghdad during the period from May to October 2004. The hepatoprotective effect of melatonin was studied through treatment of rats with single dose [10 mg Kg-1] orally, 7 days before and during the period of CPZ treatment, and 7 days after the induction of suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde [MDA] and glutathione [GSH] in liver tissue homogenate, activities of the liver aminotransferases, alanine transaminase [ALT] and aspartate transaminase [AST] in serum, in addition to serum level of bilirubin [total and conjugated] were evaluated. Liver tissue sections were examined to follow histological changes. Analysis of data showed that treatment with melatonin significantly attenuated the oxidative stress parameters as evidenced by lowering MDA levels in tissue homogenate while not affecting GSH levels. Serum activities of ALT, AST and serum bilirubin were normalized with both pre-treatment and post-treatment with melatonin. Data revealed that post-treatments with both saline and melatonin restore hepatic activity; however, melatonin showed significant reduction in ALT activity and bilirubin level than saline post-treatment. Additionally, histological evaluation revealed improvement of liver damage in this respect. The presented data indicated that orally administered melatonin in pharmacological doses protects against CPZ-induced liver disease in rats

Carbamazepine--the commonest cause of toxic epidermal necrolysis and Stevens-Johnson syndrome: a study of 7 years.

BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are a group of severe life threatening drug reactions. The drugs commonly implicated as the cause of these drug reactions vary depending on host factors and the prescription pattern of drugs in that particular area. AIM: The aim of the study was to find the drugs implicated as the cause of SJS/TEN in the patients admitted in the dermatology ward at the Medical College, Thrissur and to find the clinical outcome. METHODS: It was a retrospective study of 7 years from 1997 to 2004. The case records of all patients with a clinical diagnosis of TEN or SJS were studied in detail regarding the drugs implicated as the cause, the management and the clinical outcome. RESULTS: During the study period, 41 patients in the age group ranging from 12 to 72 years were treated as inpatients, of which 20 were males and 21 were females. The commonest drug implicated as the cause of SJS/TEN was carbamazepine (44%). The indication for carbamazepine was control of pain in more than 50% of the cases. Presence of a major systemic disease before the onset of SJS/TEN was associated with a bad prognosis. CONCLUSION: The increased use of carbamazepine, especially for control of pain, may be the reason for the increased incidence of SJS/TEN due to the same drug. Awareness about the drugs implicated in life threatening drug reactions will help physicians in preventing them by judicious use of the drugs.

Clopromazina, L-carnitina y carbonato de litio: evaluación de efectos eriprotectores in vitro ante estrés mecánico y fotohemólisis UVB / Chlorpromazine, L-carnitine and lithium carbonate: evaluation of erythoprotective efects in vitro under mechanical stress and UVB photohemolysis

Se evaluaron los efectos eritroprotectores de: Clorpromazina (CPZ), L-Carnitina (LCN) y Carbonato de Litio (Li). A las muestras de sangre de cobayos (n=15, 6mL; 1mL/vial) se añadió ringer (20µL), CPZ (20 µL; 0,5 mg.mL-¹), LCN (20µL; 4mg.mL-¹) o Li (20µL; 0,08mg.mL-¹) incubándose por 30, 60 y 90 min en rotación lenta, luego se sometieron a agitación calibrada por 10min, centrifugación (2500rpm, 15min) y determinación de Hemoglobina libre (HbL) en el sobrenadante por espectrofotometría a 415 nm. Otra serie de muestras (n=5), fueron sometidas a fotohemólisis con luz ultravioleta B (UVB) por 10 min, agregándose previamente Ringer ó LCN, comparándose con muestras sin adiciones (controles). En estrés mecánico la CPZ mostró valores de HbL mayores al Ringer a los 30 min (Mann-Whitney; Z= -3,8; p<0,001); 60 min (Z= -3,6 p<0,001) y 90 min (Z= -3,6; p<0,001). La incubaci¢n con LCN ó Li mostró valores similares al Ringer en todos los tiempos (Z<2,56; p>0,05) y significativamente menores que la CPZ (Z>3,0; pz0,001) sin diferencias entre LCN vs. Li (Z<1,0; p>0,05). En fotohemólisis UVB, la incubación con Ringer mostró valores de HbL inferiores al control (t=5,57; p<0,05) y mucho menores que los de LCN (t= 18,06; p<0,001). Las muestras controles presentaron menor HbL que aquellas con LCN (t= 3,44; p<0.05). Los resultados indican que en estrés mecánico la CPZ tiene efecto hemolítico, mientras qye la LCN y el Li no mostraron diferencias con el Ringer. En fotohemólisis UVB, la LCN no mostró efecto eritroprotector

Acute pancreatitis and diabetic ketoacidosis in non-diabetic person while on treatment with sodium valproate, chlorpromazine and haloperidol.

A nondiabetic young male patient in hypomanic phase of bipolar disorder on maintenance treatment with sodium valproate, developed transient episode of acute pancreatitis and diabetic ketoacidosis after addition of chlorpromazine and halopridol. It subsided completely within six weeks and his blood sugar was normal without any antidiabetic therapy. Simultaneous occurrence of acute pancreatitis and diabetic ketoacidosis is reported as a very rare complication of combination of antipsychotic drugs sodium valproate, chlorpromazine and haloperidol. Blood sugar should be periodically monitored in patients on sodium valproate and antipsychotic medication.

Hematopoietic growth factors in drug-induced agranulocytosis.

Drug-induced agranulocytosis (DIA) is a potentially fatal disorder. Hematopoietic growth factors have been used in the treatment of DIA. We report nine cases of DIA treated with granulocyte macrophage - colony stimulating factor (GM-CSF) in a dose of 300 microg/day. All the patients had evidence of systemic infection. Mean time to reach an absolute neutrophil count of 0.5 x 10(9)/L was three days. One patient succumbed to the disease. The cause of death was multiorgan failure. No adverse events were observed with GM-CSF. We conclude that hematopoietic growth factors are useful in shortening the period of neutropenia and reducing morbidity and mortality in these patients.

Síndrome neuroléptica maligna: relato de caso com recorrência associada ao uso de olanzapina / Neuroleptic malignant syndrome: case report with recurrence associated with the use of olanzapine

A síndrome neuroléptica maligna (SNM) consiste em reaçao idiossincrática a neurolépticos, provavelmente relacionada a bloqueio dos receptores dopaminérgicos nos gânglios da base, sendo por isso também conhecida como síndrome da deficiência aguda de dopamina. A SNM é caracterizada por hiperpirexia, alteraçao do nível de consciência, hipertonia, disfunçao autonômica e insuficiência respiratória, podendo ainda ser encontrados rabdomiólise e leucocitose. O haloperidol é a droga mais frequentemente associada à síndrome. Relatamos o caso de um paciente de 30 anos que apresentou SNM em duas ocasioes diferentes, a primeira delas relacionada ao uso de haloperidol e clorpromazina e a segunda relacionada ao uso de olanzapina, fato este sem mençao anterior na literatura indexada.

Síndrome neuroléptico maligno: aproximación médico-psiquiátrica / Malignant neuroleptic syndrome: a clinical-psychiatric approach

We report the case of a 42 years old male, with a bipolar disorder and receiving lithium therapy, valproic acid and clonazepam. Due to an exacerbation of his underlying disease, he was admitted to a psychiatric clinic and received 50 mg of intramuscular chlorpromazine in 2 ocasions. Afterwards, the patient had an alteration of conciousness, fever reaching 39ºC and generalized muscular rigidity. Laboratory work-up showed a normal brain CT scan, a diffuse slowness in the EEG and a creatinphosphokinase that reached values of 3.040 U/l. He was transferred to an intensive care unit and treated with sodium dantrolene and bromocriptine, obtaining a good clinical response

Assessment of chlorpromazine as radiation sensitizer and protector.

In vitro studies of chlorpromazine (CPZ) a popular anti-psychotic drug has shown radiation sensitizing effects at higher celluar concentration and protective effect at a lower concentration. The present study was designed to evaluate both sensitizing and protective effects in the treatment of advanced cancer of the cervix treated with hypofractionated external radiation and intratumoural injection of chlopromazine. Twenty patients were treated with intratumoural CPZ and radiation, while, 23 patients received radiation alone. A 52.94% complete response was noted in CPZ arm while 39.1% complete response in the control. A trend towards improved response is seen in CPZ group. Similarly patients who received CPZ showed significantly low proctitis rates.

Efeitos oculares associados ao padräo de uso e à dose de clorpromazina / Ocular effects related to the pattern and dose of use chlorpromazine

Os autores avaliam a influência da dose da clorpromazina no desenvolvimento de alteraçöes oculares características em 38 pacientes psiquiátricos internados no Hospital Psiquiátrico Säo Pedro (Porto Alegre, RS) em uso crônico desta droga. Vinte e dois pacientes (58 por cento) apresentaram efeitos oculares adversos, manifestados por opacificaçäo bilateral do cristalino e, em casos severos, opacificaçäo concomitante do endotélio corneano. Os pacientes foram classificados em graus crescentes de 0 a IV pigmentaçäo bilateral acentuada da cápsula anterior do cristalino em forma de estrela. A frequência das alteraçöes é analisada em relaçäo faixa etária, padräo de uso e doses utilizadas. Os autores sugerem a possibilidade de uma suscetibilidade maior em indivíduos idosos, e concluem ser a dose de clorpromazina o fator mais importante na gênese das alteraçöes oculares

Catarata estelar em pacientes näo usuários de fenotiazínicos / Stellar cataract in patients not using phenothiazines

Os autores apresentam um estudo sobre a presença de catarata estelar em um grupo de pacientes ambulatoriais com uma história negativa para o uso de derivados fenotizínicos. Com o encontro de 7 casos em 100, analisam esta frequência em sua distribuiçäo por sexos e faixas etárias, além de compará-la com dados da literatura, concluindo serem os achados concordantes com esta. Comparam ainda tais achados com os de trabalhos nos quais a casuística consistia de pacientes que usavam fenotiazínicos, concluindo que a presença da catarata estelar pode ser considerada altamente sugestiva do uso destas drogas, porém näo patognomônica