Prescribing cascade. A proposed new way to evaluate it.

Prescribing cascade is defined as the situation in which a first drug administered to a patient causes adverse event signs and symptoms, that are misinterpreted as a new condition, resulting in a new medication being prescribed. The cascade may have multiple steps and differ in complexity and severity. Despite being well identified, prescribing cascade is an increasingly common problem in medical practice. It constitutes a warning about irrational use of medicines that puts health at risk and increases treatment costs if it is not taken into account. In this article, representative cases taken from Hospital General de Agudos Dr. Cosme Argerich pharmacovigilance database were selected to assess a proper score and an algorithm that define the probable prescribing cascade.

Prescribing cascade: A proposed new way to evaluate it

Prescribing cascade is defined as the situation in which a first drug administered to a patient causes adverse event signs and symptoms, that are misinterpreted as a new condition, resulting in a new medication being prescribed. The cascade may have multiple steps and differ in complexity and severity. Despite being well identified, prescribing cascade is an increasingly common problem in medical practice. It constitutes a warning about irrational use of medicines that puts health at risk and increases treatment costs if it is not taken into account. In this article, representative cases taken from Hospital General de Agudos Dr. Cosme Argerich pharmacovigilance database were selected to assess a proper score and an algorithm that define the probable prescribing cascade.

La prescripción en cascada identifica la situación generada tras la administración a un paciente de un medicamento que le provoca un evento adverso, el cual al no ser debidamente reconocido como tal por el profesional desencadena nuevas prescripciones farmacológicas que pueden agravar o generar nuevos eventos adversos. Por ello, de acuerdo a la idiosincrasia de cada paciente, la cascada puede tener múltiples pasos y diferir en complejidad y gravedad. A pesar de estar identificada, la prescripción en cascada es un problema cada vez más común en la práctica médica y una advertencia sobre el uso irracional de los medicamentos que pone en riesgo la salud e incrementa sus costos si no se tiene en cuenta. En este artículo, se seleccionaron casos representativos tomados de la base de datos de farmacovigilancia del Hospital General de Agudos Dr. Cosme Argerich para probar un nuevo score y un algoritmo de decisión, que evalúen la supuesta cascada prescriptiva.

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

OBJECTIVE: The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. RESEARCH DESIGN AND METHODS: Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. RESULTS: Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. CONCLUSION: QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Relevancia de la farmacovigilancia hospitalaria en la práctica médica actual / Importance of pharmacovigilance in current medical practice

Las reacciones adversas medicamentosas (RAM) generan actualmente una notable morbimortalidad, llegando a representar entre la cuarta y sexta causa de muerte y hasta un 12% de las hospitalizaciones en países desarrollados. Este es, además, un problema creciente. El objetivo del trabajo fue revisar la incidencia de RAM en un hospital de alta complejidad. Se revisó la base de datos del sistema de farmacovigilancia, desde junio de 2008 hasta febrero de 2012. Para determinar la causabilidad de una droga en un evento médico se aplicó el índice de Naranjo de efectos indeseables medicamentosos. Se consideró RAM grave a aquella que provoca la internación, la prolonga, compromete seriamente la vida, genera discapacidad permanente o teratogénesis o induce la muerte. Se detectaron 2420 RAM en este período. 469 (19.38%; IC 95%: 17.80-20.95) fueron serias, principalmente debido a que fueron causa de hospitalización (n = 287). Hubo 14 muertes atribuibles a RAM. Los grupos farmacológicos más frecuentemente asociados a toxicidad fueron drogas cardiovasculares, antibióticos, neuropsiquiátricas y corticoides. Las RAM más frecuentes afectaron al sistema endocrinometabólico, causaron hepatotoxicidad, nefrotoxicidad y farmacodermias. Las causas más frecuentes de hospitalización por RAM fueron infecciones graves asociadas a tratamiento inmunosupresor y hemorragia digestiva por anticoagulación y antiinflamatorios no esteroides. La incidencia de RAM en pacientes hospitalizados y el número de hospitalizaciones por este motivo fue elevado. Las drogas involucradas fueron similares a las comunicadas en la bibliografía internacional, salvo la alta incidencia de RAM relacionadas a inmunosupresores.

Adverse drug reactions (ADRs) are cause of significant morbi-mortality They are between the fourth and sixth cause of mortality in developed countries and cause nearly 12% of hospitalizations. The objective of this publication was to analyze the incidence of ADRs in a tertiary care hospital in Buenos Aires City. The hospital phamacovigilance database for the period June 2008- February 2012, was analyzed. The Naranjo score was applied to assess drug causality. We consider serious an ADRs when it potentially compromised life, induced hospitalization or prolonged it, caused discapacity, teratogenesis or death. In this period, a total of 2420 ADRs were detected: 469 (19.38%; CI 95%: 17.80 - 20.95) were serious, mainly because they induced hospitalization (n = 287). There were 14 ADRs-related deaths. Cardiovascular and neuropsychiatric drugs, antibiotics and corticoids were those most frequently related to toxicity. Endocrine-metabolic disorders, hepatotoxicity, nephrotoxicity and pharmacodermy were the most frequently involved. Among the ADR most frequently associated to hospitalization were Immunosuppressant-associated severe infections and upper gastrointestinal bleeding related to oral anticoagulants and non steroids anti-inflammatory drugs. The ADRs incidence in hospitalized patients and ADRs related hospital admissions were considered relatively high. Drugs involved were similar to those reported in the international bibliography except for the higher incidence of immunosuppressants related admissions here observed.

[Importance of pharmacovigilance in current medical practice]. / Relevancia de la farmacovigilancia hospitalaria en la práctica médica actual.

Adverse drug reactions (ADRs) are cause of significant morbi-mortality They are between the fourth and sixth cause of mortality in developed countries and cause nearly 12% of hospitalizations. The objective of this publication was to analyze the incidence of ADRs in a tertiary care hospital in Buenos Aires City. The hospital phamacovigilance database for the period June 2008- February 2012, was analyzed. The Naranjo score was applied to assess drug causality. We consider serious an ADRs when it potentially compromised life, induced hospitalization or prolonged it, caused discapacity, teratogenesis or death. In this period, a total of 2420 ADRs were detected: 469 (19.38%; CI 95%: 17.80 - 20.95) were serious, mainly because they induced hospitalization (n = 287). There were 14 ADRs- related deaths. Cardiovascular and neuropsychiatric drugs, antibiotics and corticoids were those most frequently related to toxicity. Endocrine-metabolic disorders, hepatotoxicity, nephrotoxicity and pharmacodermy were the most frequently involved. Among the ADR most frequently associated to hospitalization were Immunosuppressant-associated severe infections and upper gastrointestinal bleeding related to oral anticoagulants and non steroids anti-inflammatory drugs. The ADRs incidence in hospitalized patients and ADRs related hospital admissions were considered relatively high. Drugs involved were similar to those reported in the international bibliography except for the higher incidence of immunosuppressants related admissions here observed.

Drug-induced liver injury caused by adalimumab: a case report and review of the bibliography.

The most serious adverse drug reaction of adalimumab (ADR) is tuberculosis reactivation. We describe a case of a 35-year-old man, with rheumatoid arthritis (RA) and hepatitis C virus genotype 1a with a liver biopsy in 2001 with a METAVIR score pattern A1 F0; he received interferon alpha 2b for six months, but treatment was suspended because of reactivation of RA. Liver function tests after treatment were similar to previous ones showing a minimal cholestatic pattern. In 2008, methotrexate was prescribed, but the drug was withdrawn at the third month because of the appearance of pruritus and Ggt rise. Viral load at that moment was 9300000 UI/mL, log 6,9. The liver biopsy showed a Metavir Score A2 F1. Adalimumab was started in 2010, and at the third month of treatment, Ggt showed a rise of 23 times normal value (NV), alkaline phosphatase 2,5 times NV with AST and ALT with no change. A new liver biopsy showed portal inflammation with eosinophils and a METAVIR A1 F2. We think that adalimumab appears to be responsible for the liver injury, because of temporal relationship, liver biopsy findings, other clinical conditions being discarded, and the improvement of clinical symptoms and biochemical abnormalities when adalimumab was suspended.

Toxicidad renal generada por medicamentos / Drug-induced renal toxicity

La nefrotoxicidad por drogas es un evento médico frecuente en pacientes hospitalizados. El control estricto de la función renal y evitar la combinación de drogas nefrotóxicas puede disminuir la aparición o la gravedad de esta toxicidad.

Mechanisms of drug induced QT interval prolongation.

The long QT syndrome (LQTS) is characterized by a prolonged QT interval, as well as a propensity to develop syncope and sudden cardiac death caused by the malignant polymorphic ventricular arrhythmia called torsades de pointes (TdP). The QT interval is measured from the onset of the QRS complex to the end of the T wave and can be affected by both ventricular conduction velocities as well as by the velocity of repolarization. In most cases, QT prolongation is caused by factors that prolong the duration of the action potential, mainly by delaying the repolarization phase 3. The molecular mechanism is partially known. There are two well described mechanisms: blocking of the ion channel cavity of HERG; or causing an abnormal protein trafficking required for the location of HERG subunits in cell membrane. Both of them impair the I(Kr) current. However the blockade of ion channels is not the only condition to generate TdP. Other factors may play an important role, e.g. myocardium heterogeneity, drug-drug interaction, genetic polymorphism, and Electrolyte disturbances. Several drugs had been subject of withdrawal because QT-prolongation and arrhythmia. Understanding of processes involved in drug-induced QT prolongation is needed for the study and prevention of life-threatening arrhythmias.

Other drugs acting on nervous system associated with QT-interval prolongation.

Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some preparations used for treatment of cough. These drugs have a narrow therapeutic interval or possible drug interactions that lead to clinical toxicity manifested by arrhythmias. They share the ability to block potassium channels (HERG), prolong the action potential and QT interval, and generate arrhythmias and Torsades de Pointes like other typicality recognized like antiarrhythmics, antihistamines, prokinetics, psychotropics and anti-infectives agents. Muscle relaxants like alcuronium, pancuronium and atracurium associated with or without atropine prolong significantly the QT interval. Methadone is the opiod most tightly associated with QTc prolongation; with much lesser potency buprenorphine and oxycodone can block HERG channels and depress the IKr current in vitro.Antineoplastic chemotherapy like anthracyclines, alkylating drugs, alkilants and cisplatin are associated with electrocardiographic alterations including prolongation of QT and emesis of different grades. It's very important take in account the synergic effects over the QT prolongation when effective antiemetics like 5-HT3 receptor antagonist (granisetron, ondansetron, and dolasetron) are administered. The Knowledge of their pharmacological properties is of vital importance to avoid exposing particularly vulnerable individuals as those with congenital long QT syndrome, and even the general public to unnecessary risk of potentially fatal arrhythmias.

Farmacovigilancia en sala de clínica médica / Pharmacosurveillance in a clinical department centre

Las reacciones adversas a medicamentos representan entre el 5 y 10 por ciento de las internaciones y son la quinta o sexta causa de muerte en países desarrollados. La farmacovigilancia es una herramienta fundamental para disminuir la morbimortalidad producida por drogas... Las drogas son causa frecuente de prolongación de internación así como también de aumento de la morbimortalidad en pacientes hospitalizados.