Uso de la farmacogenética en el diagnóstico diferencial. A propósito de un caso / No disponible

Presentamos el caso clínico de un niño de 8 años con un trastorno por déficit de atencióne hiperactividad que desarrolló un cuadro clínico compatible con psicosis después deluso de metilfenidato en dosis terapéutica. Ante tan grave reacción adversa se le realizó unestudio farmacogenético para intentar dilucidar la causa de dicha reacción. Se estudiaronlos alelos 3*, 4*, 5* y 6* de la enzima CYP2D6 por amplificación en PCR buscando si el pacienteera un metabolizador pobre.Caso clínico: varón de 8 años sin antecedentes de interés que, tras el uso de metilfenidatoen dosis de 5 mg/día durante dos años tiene una buena respuesta clínica y un rendimientoescolar adecuado. Acude a la consulta ambulatoria por presentar un cuadro dehipotonía, bradipsiquia y dificultad en la articulación de la palabra, alternando con verborreay desconexión del medio. Se deriva a urgencias hospitalarias donde, tras la supresiónde la medicación, la sintomatología remitió hasta desaparecer. Todos los estudioscomplementarios fueron normales (hemograma, bioquímica, punción lumbar, electroencefalogramay resonancia magnética nuclear). Cuatro semanas después de este evento elpaciente reinició la medicación reapareciendo el cuadro clínico, que desapareció tras susupresión.La normalidad del estudio genético descarta una alteración farmacocinética relacionadacon la reacción adversa. Este efecto secundario probablemente se deba al uso prolongadode metilfenidato y a los niveles de dopamina mediados por CYP2D6

We present the clinical case of an 8 year old child with attention deficit hyperactivity disorder(ADHD), who developed a psychopathological disorder compatible with acute psychosisafter two years of using therapeutic doses of methylphenidate. We performed a pharmacogeneticstudy in order to find the cause of the serious adverse reaction. Biochemical amplificationby PCR of CYP2D6 and its alleles, 3*, 4*, 5* and 6* was done to find if the reaction was toxic,if the patient had a poor metabolizer genotype. Clinical case: an 8 year old male patient, withoutantecedents, who was being successfully treated for two years with methylphenidate at 5mg/day orally for ADHD, with goodscholastic results as well. The patient went to ambulatoryemergency complaining of hypotonia, bradypsychia and difficulty articulating words with intervalsof verbosity, speech disconnected with reality and having periods of complete verbal absence.The patient was admitted in the pediatric unit. After suspending medication, the clinicalsymptoms improved until they disappeared. Blood profile as well as biochemical complementarytests were normal. A nuclear magnetic resonance (NMR) did not reveal organic alterationwhich could have explained the symptoms. EEG was also normal. After rechallenge, one monthafter the first event, the boy developed the same symptoms. A CYP2D6 genotype analysis wasdone (3*, 4*, 5* y 6* alleles) where we found him to be a normal metabolizer. This discards apharmacokinetic alteration of genetic origin, which could explain an abnormal reaction tomethylphenidate. This adverse reaction could be due to the prolonged use of this drug and theaction of CYP2D6 in the levels of dopamine

Analysis of narcotic analgesic usage in the treatment of postoperative pain.

We reviewed 526 medical records of surgical patients and interviewed 81 of these patients. We also sent questionnaires to house staff (57 of 97 responded) and nurses (70 of 142 responded) involved in the care of these patients. A substantial number of patients suffered at least moderate pain during the postoperative period despite analgesic medication. Patients received 70% of the maximal ordered analgesic dose in the first 24 hours. Physicians prescribed drugs in doses that were often inadequate and to be given at inflexible intervals. The optimal doses and duration of action of meperidine, as judged by the house staff and nurses, did not agree with the accepted pharmacologic profile of this drug.

A comparison of drug product information in four national compendia.

Four widely used compendia of prescribing information have been received to examine the way in which some drug companies recommend uses for several anti-inflammatory products and describe the major dangers in their use. The Physician's Desk Reference (PDR) cites the greatest absolute number of indications for steroids with systemic action, as well as the greatest number of contraindications, warnings and precautions, and adverse effects. The total number of precautions appearing in the PDR is three times the mean for the other compendia, and the number of adverse effects is four times the mean of the others. Together, these other compendia contain 70.5% of the number of words in the PDR. The PDR contains statements that are strongly directive for the physician and that do not appear in the other compendia. Regulatory and social differences may at least partially explain these discrepancies.

Attitudes of patients, housestaff, and nurses toward postoperative analgesic care.

A survey was carried out among housestaff and nurses involved with postoperative patient care to assess their knowledge of analgesics and their attitudes toward postoperative analgesic care. Only one-fifth of the respondents prescribed for complete pain relief. There were some misconceptions about adding other drugs to narcotic analgesics as well as fear of the addictive properties of these narcotics. The respondents lacked confidence about their knowledge of narcotic analgesics. Fear of respiratory depression was less prominent. Nine percent of the physicians and 31% of the nurses believed that response to a placebo indicates factitious pain. Fifty-four percent of the physicians and 74% of the nurses believed that patients receive adequate pain relief. Eighty-one patients were questioned on their beliefs about pain and its relief. Sixty-six of these were monitored postoperatively to assess the effectiveness of pain relief, which was judged by the authors to be ineffective (i.e., moderate to severe pain at the peak of analgesia) in 41%. Seventy-five percent of the patients reported that their overall postoperative pain relief had been adequate. There was no correlation between the amount of analgesic required postoperatively and either the degree to which patients believed pain builds character or the degree to which they rated themselves sensitive to pain. This study emphasizes the need for better and more comprehensive training of housestaff and nurses in analgesic care.

Antithrombin III contribution to cholestasis differential diagnosis: its correlation with one stage prothrombin time and factor V.

Levels of antithrombin III (AT III) measured by two different methods, Factor V (FV) and One Stage Prothrombin Time, have been studied in two groups of patients: 55 with chronic liver disease and 22 with extra hepatic cholestasis. Results show a statistically significant correlation between the decrease of AT III and FV in the first group, and the normality of these parameters (unrelated to One Stage Prothrombin Time) in the second group. Levels at AT III and FV correlate directly with the functional integrity of hepatic parenchyma, so they may help in the differential diagnosis of different types of cholestasis.