Estudio de mortalidad de pacientes en tratamiento con digoxina y trazodona / Study of mortality on patients with digoxin and trazodone treatment

Objetivos: Analizar la influencia de trazodona en la mortalidad de pacientes en tratamiento con digoxina. Material y métodos: Estudio observacional retrospectivo comparativo de mortalidad de pacientes en tratamiento concomitante con digoxina y trazodona versus digoxina. El período de estudio fue de un año (1 de mayo de 2020 hasta 30 de abril de 2021). Las variables recogidas fueron edad, sexo, indicación, dosis de digoxina y trazodona, fecha de inicio de trazodona, fecha fin de digoxina y trazodona, número total de fármacos prescritos, éxitus y fecha de éxitus. El análisis estadístico se realizó mediante la aplicación Stata®. Versión 14.2. Resultados: Se incluyeron 644 pacientes en tratamiento con digoxina, 73 en el grupo con trazodona y 571 en el grupo sin trazodona. Al final del periodo estudiado se registraron 73 muertes, observándose una mortalidad del 34,3% en el grupo de digoxina y trazodona, y del 8,4% en el grupo de digoxina. Las variables relacionadas con el riesgo de muerte fueron tratamiento con tradozona, edad y número de tratamientos prescritos. Conclusiones: Los resultados del estudio sugieren un incremento del riesgo de mortalidad en pacientes de edad avanzada en tratamiento con digoxina y trazodona. La falta de evidencia de uso de trazodona como hipnótico, la interacción farmacocinética entre ambos fármacos y el perfil de seguridad de trazodona, hace necesario una estrecha monitorización de los pacientes o valorar alternativas con mayores evidencias de seguridad.(AU)

Objectives: To evaluate the trazodone influence on the mortality of patients treated with digoxin. Material and methods: Retrospective, observational, comparative study that included patients receiving trazodone and digoxin concomitantly and patients on digoxin treatment without trazodone between April 2020-April 2021. Age, sex, drug indication, digoxin and trazodone dosage, start and end dates of trazodone use, digoxin end date, number of prescribed drugs and death date were the variables we paid attention to. Statistical analysis was performed using the Stata® application. Version 14.2. Results: 644 patients were included, 73 in the group digoxin with trazodone and 571 in the group without trazodone. At the end of the study period, 73 deaths were recorded. Mortality in the digoxin and trazodone group were 34.3% and 8.4% in the digoxin group. The variables related to the risk of death were treatment with trazodone, age and number of prescribed treatments. Conclusions: The results of the study suggest an increased risk of mortality in elderly patients in treated with digoxin and trazodone. The lack of evidence in the use of trazodone as a hypnotic, the pharmacokinetic interaction between both drugs and the safety profile of trazodone, makes it necessary to closely monitor patients or assess therapeutic alternatives with more evidence to be sure its use is safe.(AU)

Análisis de la utilización de medicamentos biosimilares / No disponible

No disponible

Cannabis derivatives therapy for a seronegative stiff-person syndrome: a case report.

WHAT IS KNOWN AND OBJECTIVE: Stiff-person syndrome (SPS) is an uncommon and disabling disorder characterized by progressive rigidity and episodic painful spasms involving axial and limb musculature. SPS treatment is mostly based on benzodiazepines, baclofen, immunosuppressants and intravenous immunoglobulin. Cannabis derivatives [tetrahydrocannabinol (THC) and cannabidiol (CBD)] are available as an oromucosal spray (Sativex(®)), indicated as add-on treatment, for symptom improvement in patients with moderate to severe spasticity because of multiple sclerosis (MS). Our objective is to report a case of seronegative SPS successfully treated with THC-CBD oromucosal spray. CASE SUMMARY: We report a case of a 40-year-old man presenting with progressive muscle stiffness and intermittent spasms for 6-years. The diagnosis of stiff-person syndrome was based on the clinical features and neuroelectrophysiologic findings of continuous motor unit activity. Glutamic acid decarboxylase autoantibodies was absent in our patient, in both serum and cerebrospinal fluid (CSF). Cannabis derivatives oromucosal spray was introduced after a series of unsatisfactory traditional medical treatments. After 14 months treated with THC-CBD oromucosal spray, improvement was verified in the eight dimensions of the scale of SF-36 quality of life questionnaire. WHAT IS NEW AND CONCLUSION: Clinical experience with cannabis derivatives in patients with multiple sclerosis is accumulating steadily, but there is no current literature about its efficacy for SPS. Because MS and SPS share some neurological symptoms such as spasticity and rigidity, it is thought that THC-CBC can be an option for SPS patient. Our case report suggests that THC-CBD oromucosal spray is an alternative treatment for patients with refractory SPS, and further validation is appropriate.

[Integral computerization of health care for inpatients. Impact on primary care activities]. / Informatización integral de la asistencia sanitaria en el paciente hospitalizado. Repercusión sobre las actividades de atención farmacéutica.

INTRODUCTION: Due to its iatrogenic potential and economic impact, drug prescription is one of the most complex tasks within the health care process. Electronic prescription systems (EPS), and particularly expert systems, increase quality by reducing errors in the prescribing and dispensing processes. Besides, electronic prescription reduces costs. On the other hand, it demands a new equilibrium in the delivery of pharmaceutical services. METHOD: The EPS established at "Hospital de la Ribera" is described. This system is basically characterised by: (1) its integration within the electronic global system throughout a computer network; (2) drugs are ordered directly by physicians in the electronic system; (3) pharmacists access the whole clinical record of patients "in situ"; (4) and integration of clinical activities by pharmacists in the patient medical record. The impact of this system on pharmaceutical care activities such as identification, reporting and documentation of drug-related problems (DRPs) versus traditional approaches is analysed. RESULTS: Access to patient information throughout the system facilitates DRP identification, with a resulting overall prevalence of clinically relevant drug-related problems of 9%. CONCLUSION: The model implemented in our hospital favours the development of clinical activities by pharmacists as it allows communication among health care professionals, activities are permanently recorded in patient medical charts, and a formal document of pharmacist involvement and compromise with the clinical progress and outcome of patients ensues.

Informatización integral de la asistencia sanitaria en el paciente hospitalizado. Repercusión sobre las actividades de atención farmacéutica / Integral computerization of health care for inpatients. Impact on primary care activities

Introducción: La prescripción de medicamentos es una de las tareas más complejas dentro del proceso asistencial, tanto por su potencial iatrogénico, como por su impacto económico. El desarrollo de los sistemas de prescripción informatizada (SPI), y en particular los sistemas expertos, supone una mejora en la calidad asistencial en la medida en que disminuyen los errores en la prescripción y dispensación al tiempo que reducen los costes. Por otra parte, su implantación motiva el establecimiento de un nuevo equilibrio en la provisión de los servicios farmacéuticos. Método: Se describe el sistema de prescripción electrónica establecido en el Hospital de la Ribera que se caracteriza por: a) formar parte del sistema informático integral del hospital; b) la prescripción la realiza directamente el médico en el sistema informático; c) dispone de acceso in situ a la totalidad de la historia clínica del paciente; y d) integra las actividades de atención farmacéutica en la historia clínica del paciente. Se analiza la repercusión del sistema sobre las actividades de atención farmacéutica de identificación, comunicación y documentación de problemas relacionados con los medicamentos (PRM) frente al sistema tradicional de revisión de la historia farmacoterapéutica. Resultado: El acceso a la información del paciente a través del sistema facilita la identificación de PRM, de manera que la prevalencia global de problemas relacionados con el medicamento con relevancia clínica se sitúa en el 9 por ciento. Conclusiones: El sistema descrito facilita la identificación de problemas relacionados con los medicamentos, la comunicación con el equipo asistencial y permite documentar las actividades de atención farmacéutica en la historia clínica del paciente. (AU)

Effect of vigabatrin on the pharmacokinetics of carbamazepine.

OBJECTIVE: To evaluate a possible interaction between vigabatrin and carbamazepine in epileptic patients. METHODS: Steady-state serum concentrations of carbamazepine with and without vigabatrin were compared. The study group consisted of 15 patients (eight females, seven males, and mean age 31 +/- 12 years), with refractory partial epilepsy. They received vigabatrin as add-on therapy. Patients received carbamazepine monotherapy for at least 6 months and the carbamazepine-vigabatrin combination for at least 3 months. Blood samples were obtained in the morning, before the first daily dose and the carbamazepine plasma concentrations were analysed by fluorescence polarization immunoassay (TDx System). RESULTS: No statistically significant differences were found in mean carbamazepine daily dose. Mean trough concentrations were 7.9 +/- 1.4 microg/mL with carbamazepine alone, and 6.5 +/- 2.0 microg/mL with carbamazepine-vigabatrin association (P < 0.03). The mean values of pharmacokinetic parameters were: level/dose ratio (L/D) = 0.59 +/- 0.20 vs. 0.45 +/- 0.15 (P < 0.05) and plasma clearance (Cl) = 78.5 +/- 25.8 vs. 105.8 +/- 38.9 mL/h/kg (P < 0.05), with carbamazepine alone and carbamazepine-vigabatrin combination, respectively. CONCLUSION: Vigabatrin produced a statistically significant increase in the plasma clearance of carbamazepine when the two drugs were given simultaneously.

Placental transfer and neonatal effects of propofol in caesarean section.

OBJECTIVE: To assess transplacental passage of propofol by measuring the levels in maternal and foetal plasma, and the possible relationship between the latter and the neonatal effects when propofol is used as an induction agent in obstetric anaesthesia for performing a caesarean section to terminate pregnancy. METHODS: Intravenous propofol was administered as an anaesthesia-inducing agent at doses of 2 mg/kg in 10 healthy women (ASA I-II). The propofol concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: After induction, hypnosis was achieved in all patients within 75 s, and it took 4-10 min to deliver the foetus. Apgar test scores were high in seven of the 10 neonates, in three cases the score was 5 or less. The mean values in venous maternal blood were 5.01+/-1.06 microg/ml 1 min after propofol administration and 1.47+/-0.35 microg/ml at the time of delivery. Propofol crossed the placental barrier with levels in the umbilical cord of 0.32+/-0.10 microg/ml in the vein and 0.22+/-0.08 microg/ml in the artery. CONCLUSION: Propofol plasma levels in the newborn at the time of delivery depend on the level in maternal plasma, and therefore on the dose used for induction and the time lapsed between the administration of the drug and the delivery of the foetus.

Valproic acid clearance in children with epilepsy.

OBJECTIVE: To evaluate population pharmacokinetics and the relationship between plasma concentration and daily dose of valproic acid (VPA) in a homogeneous group of children with epilepsy. METHODS: One hundred and fifty-one steady-state VPA plasma level measurements were made in 62 children aged 8 months to 6 years who were receiving VPA monotherapy. RESULTS: The level:dose ratio increased with age, its mean value was 1.7 in children aged under 2 years, 2.1 in children aged 2.4 years and 3.3 in children aged 4.6 years. Weight-adjusted values of VPA clearance (Cl) decreased with increasing age. The Cl values in these three age groups were 24.5+/-12.4 ml/kg/h, 19.9+/-6.1 ml/kg/h and 12.7+/-3.0 ml/kg/h, respectively. The relationship between VPA clearance and age was: Cl (ml/kg/h)=47.6 x age (months)(-0.29), (r=-0.87). This equation allows the estimation of VPA plasma clearance on the basis of the child's age, within the range 8-72 months. Therefore, it can be used to establish the initial maintenance paediatric dose of VPA in monotherapy. CONCLUSION: The relationship between clearance and age should be useful when establishing a pharmacokinetic programme for VPA monotherapy in children.

Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.

OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.

[Pharmacokinetics of lidocaine in obstetric patients after its epidural single-dose administration]. / Farmacocinética de la lidocaína en pacientes obstétricas tras su administración epidural en dosis única.

OBJECTIVE: To determine the concentrations of lidocaine in maternal plasma and to establish the kinetic constants following absorption of a single dose of lidocaine in obstetric epidural anesthesia. PATIENTS AND METHOD: Epidural blockade was provided to 10 patients by a single injection of lidocaine at doses of 200 to 300 mg (265 +/- 35 mg). The plasma concentrations of lidocaine were determined 1, 5, 10, 15, 20, 40, 60, 120 and 180 min later and at the moment of birth, by way of polarized immunofluorescence (PIF) with a Tdx automatic analyzer (Abbott). RESULTS: Time until peak plasma concentration was 17.4 min. Peak concentrations ranged from 1.44 to 2.12 micrograms/ml. Plasma clearance took place at a rate of 10.1 +/- 1.7 ml/min/kg, more slowly than in surgical patients. Duration of anesthesia ranged from 40 to 80 min and was sufficient in all cases, even for women undergoing cesarean section. At birth (25 +/- 5 min after epidural injection), plasma concentration was 1.67 +/- 0.28 micrograms/ml. CONCLUSION: Injection of 200-300 mg of lidocaine provides good analgesia during childbirth, even when cesarean section is practiced, with no toxic effects for the mother.

Plasma concentrations of vigabatrin in epileptic patients.

OBJECTIVE: To measure plasma concentrations of vigabatrin in a group of 30 adult epileptic patients with complex partial seizures (CPS) refractory to conventional antiepileptic drugs. With a view to better defining the drug's dose-response relationships in the presence of concomitant alternative antiepileptic drugs. METHODS: High-performance liquid chromatographic analysis of blood samples drawn at steady-state trough levels from patients receiving vigabatrin. RESULTS: The steady-state plasma concentrations of vigabatrin showed marked interpatient variability (CV = 59.5%). The mean concentration was 42 +/- 25 micrograms/ml (range 11.5-102.7 micrograms/ml). Nineteen patients (63%) had plasma levels between 20 and 60 micrograms/ml. The plasma clearance of vigabatrin ranged from 0.24 to 1.37 ml/min/kg (mean +/- SD = 0.74 +/- 0.40 ml/min/kg), with a median value of 0.64 ml/min/kg. Concomitant treatment with carbamazepine increased the plasma clearance of vigabatrin from 0.59 ml/min/kg (monotherapy), 0.54 ml/min/kg (co-treated with phenobarbital) and 0.41 ml/min/kg (co-treated with valproic acid) to 0.92 ml/min/kg. CONCLUSION: Vigabatrin plasma levels show wide interpatient variability, and co-administration with carbamazepine increases vigabatrin's clearance. While there is no relationship between plasma level and anti-epileptic effect, abnormally high levels of the drug may increase toxicity.

Caffeine test assessment for measuring liver function in critically ill patients.

Caffeine elimination was studied in 73 patients admitted to an intensive care unit, 33 of whom had liver disease. Mean plasma clearance of caffeine in patients with no liver disease (1.30 +/- 0.79 ml/kg/min) was significantly higher than in patients with liver disease (0.39 +/- 0.23 ml/kg/min). Mean half-life of caffeine in patients with liver disease (23.96 +/- 12.19 h) was significantly higher than in patients with no liver disease (7.25 +/- 3.04 h). No significant differences in distribution volumes were found. Receptor-operator curves (ROC) for plasma clearance and the half-life of elimination of caffeine showed a high diagnostic value. Therefore, the parameters for caffeine biotransformation, i.e. Cl and t1/2, are useful for assessing liver function in the population studied.

Treatment of nephrotic syndrome associated with idiopathic rapidly progressive glomerulonephritis and cyclosporin A.

Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response.

Pharmacokinetics of intravenous caffeine in critically ill patients.

The pharmacokinetics of intravenous caffeine used to measure liver function were evaluated in 20 critically ill patients. Each patient received a single dose of 3.0 mg/kg of caffeine benzoate as a 30-min i.v. infusion. Caffeine serum concentrations were analysed by an enzyme-multiplied immunoassay technique (EMIT). Caffeine pharmacokinetics fitted an open one-compartment model. The mean value for the half-life (t1/2) was 9.46 +/- 4.32 h, the volume of distribution was 0.55 +/- 0.13 l/kg, and the plasma clearance (Cl) was 0.85 +/- 0.44 ml/min/kg. The pharmacokinetics parameters of caffeine in critically ill patients compared with normal volunteers were characterized by a reduction in plasma clearance and prolongation in plasma half-life, whereas the volume of distribution remained unchanged.

Pharmacokinetics of intravenous midazolam during epidural anaesthesia.

Midazolam concentration curves versus time were analysed in 10 otherwise healthy patients (ASA I-II) with inferior limb pathologies. The benzodiazepine was used as an adjuvant agent to epidural anaesthesia in view of its lower residual effect compared with other intravenous benzodiazepines. Midazolam pharmacokinetics in these patients fitted an open two-compartment model. The plasma levels versus time corresponded to a biexponential process with a very rapid distribution phase (t1/2a = 5.7 +/- 2.4 min) and an elimination phase (t1/2 beta = 66 +/- 37 min). Mean values for distribution volumes in the central compartment and extrapolated values were Vc = 0.12 +/- 0.04 l/kg and V beta = 1.28 +/- 0.92 l/kg. This kinetic behaviour explains the rapid but short duration of midazolam action. The induction time, estimated from the start of hypnosis (eye closure), was from 60 to 120 s with i.v. injection. The duration of action for the dose administered was from 15 to 60 min, with plasma levels below 90 ng/ml upon eye opening.

[Pharmacokinetics of mepivacaine and lidocaine after epidural administration]. / Farmacocinética de la mepivacaína y de la lidocaína tras su administración epidural.

We compare plasma concentrations of mepivacine (MPV) and lidocaine (LDC) after epidural injection in 20 patients. Samples were drawn at 1, 5, 10, 15, 20, 60, and 120 minutes after administration. Absorption from epidural space is equally fast for both anesthetic agents (t max 20 +/- 7 minutes for MPV and 25 +/- 12 minutes for LDC) resulting in high values of Cmax: 7.8 +/- 3.3 microg/ml for MPV and 2.6 +/- 0.7 microg/ml for LDC (p less than 0.001). Mean values of K and Vd were 0.0076 +/- 0.0020 minutes-1 for MPV versus 0.0087 +/- 0.0032 minutes-1 for LDC and 0.9 +/- 0.7 1/kg for MPV versus 1.8 +/- 0.6 1/kg for LDC (p less than 0.001).

Theophylline plasma clearance in critically ill geriatric patients receiving total parenteral nutrition and in control patients.

Mean values and standard deviations are reported for theophylline plasma clearance in 45 hospitalized geriatric patients (age greater than 65 years), distributed into two groups: Group I (n = 24) included critically ill patients admitted to the ICU on total parenteral nutrition (TPN). Group II (n = 21) included patients admitted to the Internal Medicine Ward without TPN. All patients were treated with a constant intravenous infusion of aminophylline. Group I patients had a lower mean theophylline clearance of 0.42 +/- 0.23 ml/kg/min compared to Group II 0.64 +/- 0.24 ml/kg/min (P = 0.003).

[Systemic absorption of 2% lidocaine from the lumbar epidural space]. / Absorción sistémica de la lidocaína al 2% desde el espacio epidural lumbar.

The curves of lidocaine (LDC) plasma levels versus time were evaluated in a group of 16 patients receiving single epidural injections of 2% LDC for each metamer to be anesthesized. LDC absorption from epidural space is fairly rapid (tmax = 17 +/- 4 min and t1/2a = 6.2 +/- 1.7 min). This results in very shape peak plasma levels (2.97 +/- 0.87 micrograms/ml with 2% LDC). The remaining pharmacokinetic parameters were: Ke = 0.0057 +/- 0.0022 min-1 and Vd = 1.5 +/- 0.5 l/kg. In all patients adequate levels for operation were obtained.

Clinical pharmacokinetics of intravenous flecainide in critically ill patients.

Plasma flecainide (FLC) levels versus time were measured in a group of 10 acute myocardial infarction (AMI) patients at our Intensive Care Unit. These patients were treated with single doses of 150 mg FLC as a 30-min intravenous infusion. Mean FLC plasma concentration values at 0, 1, 2, 4, and 8 h following administration were 562 +/- 271, 342 +/- 129, 270 +/- 90m, 240 +/- 80 and 210 +/- 60 ng/ml, respectively. Flecainide pharmacokinetics fitted an open two-compartment model, with a rapid distribution phase and a slow elimination phase. Mean values for the terminal plasma half-life (t1/2 beta) was 22.0 +/- 9.7 h and the volume of distribution (V beta) was 7.99 +/- 3.02 1/kg. FLC is different to other i.v. antiarrhythmics in having a prolonged plasma half-life which is a decided advantage. In contrast to lidocaine, FLC has a pharmacokinetic profile that enables it to be used for treating ventricular arrhythmia without constant-rate i.v. infusion and without the need for complicated loading dosages in order to avoid a 'pharmacokinetic dip' over the first hour of treatment.