Antiparkinsonian Medication Reconciliation as a Strategy to Improve Safety by Preventing Medication Errors.

Background: About 70% of neurologists report that PD patients do not get their medication properly when hospitalized, and 33% are prescribed contraindicated drugs. Objectives: To execute medication reconciliation (MedRec) focused on antiparkinsonian drugs to identify, characterize and, eventually, prevent medication errors, thus promoting therapeutic quality and safety in daily practice. Methods: An interventional, single-center, 1 year, prospective study. All the patients who were hospitalized and had, at least, one active prescription containing an antiparkinsonian drug at hospital admission were included. MedRec was performed by following a three-phased check: inpatient electronic prescription validation after assessing the outpatient medication schedule, review of the latest clinical report emitted by the Neurology Department/General Practitioner, and pharmacist-driven interview of the patient and/or caregiver to confirm the information regarding medication gathered. Results: A total of 171 admission episodes from 132 patients were registered (February 1, 2021, and January 31, 2022). Of 224 prescription lines involving antiparkinsonian drugs, 179 contained, at least, one medication error (59.8%). Commission errors (91.62%) were more frequent than omitted drugs (8.38%). The most common medication errors were related to timing (41.90%), frequency (21.23%), and dosing (19.55%). The implementation of this program prevented the erroneous administration of 2716 antiparkinsonian doses, 60% of the total number of doses prescribed. Interestingly, a significant relationship between the number of medication errors and having levodopa prescribed was evidenced (P < 0.05). A contraindicated drug was prescribed in almost one-third of the episodes (29.82%). Conclusions: Clinical pharmacists' implementation of an antiparkinsonians reconciliation program sharply reduced medication errors and prescription of contraindicated drugs.

Palliative Sedation in COVID-19 End-of-Life Care. Retrospective Cohort Study.

Background and Objectives: Descriptions of end-of-life in COVID-19 are limited to small cross-sectional studies. We aimed to assess end-of-life care in inpatients with COVID-19 at Alicante General University Hospital (ALC) and compare differences according to palliative and non-palliative sedation. Material and Methods: This was a retrospective cohort study in inpatients included in the ALC COVID-19 Registry (PCR-RT or antigen-confirmed cases) who died during conventional admission from 1 March to 15 December 2020. We evaluated differences among deceased cases according to administration of palliative sedation. Results: Of 747 patients evaluated, 101 died (13.5%). Sixty-eight (67.3%) died in acute medical wards, and 30 (44.1%) received palliative sedation. The median age of patients with palliative sedation was 85 years; 44% were women, and 30% of cases were nosocomial. Patients with nosocomial acquisition received more palliative sedation than those infected in the community (81.8% [9/11] vs 36.8% [21/57], p = 0.006), and patients admitted with an altered mental state received it less (20% [6/23] vs. 53.3% [24/45], p = 0.032). The median time from admission to starting palliative sedation was 8.5 days (interquartile range [IQR] 3.0-14.5). The main symptoms leading to palliative sedation were dyspnea at rest (90%), pain (60%), and delirium/agitation (36.7%). The median time from palliative sedation to death was 21.8 h (IQR 10.4-41.1). Morphine was used in all palliative sedation perfusions: the main regimen was morphine + hyoscine butyl bromide + midazolam (43.3%). Conclusions: End-of-life palliative sedation in patients with COVID-19 was initiated quite late. Clinicians should anticipate the need for palliative sedation in these patients and recognize the breathlessness, pain, and agitation/delirium that foreshadow death.

[Pharmacokinetics and pharmacodynamics of the new oral anticoagulants dabigatran and rivaroxaban]. / Farmacocinética y farmacodinamia de los nuevos anticoagulantes orales.

Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme.

Farmacocinética y farmacodinamia de los nuevos anticoagulantes orales / Dabigatran and rivaroxaban, new oral anticoagulants for the treatment of venous thromboembolism

Dabigatran es el primer anticoagulante inhibidor directo de la trombina disponible por vía oral. La absorción del profármaco dabigatran etexilato y su conversión a dabigatran es rápida (concentraciones máximas de 4-6 h tras cirugía y 2 h posteriormente) y, pese a la baja biodisponibilidad oral, presenta escasa variabilidad entre individuos. Inhibe específica y reversiblemente la trombina, la enzima llave de la cascada de la coagulación. Los estudios tanto en voluntarios sanos como en pacientes sometidos a cirugía ortopédica mayor muestran un perfil pk/pd predecible, lo que permite regímenes fijos de dosificación. El efecto anticoagulante se correlaciona bien con las concentraciones plasmáticas del fármaco, lo que aúna una efectiva anticoagulación con un bajo riesgo de hemorragia. La excreción es mayoritariamente renal (lo que condiciona su dosificación en pacientes ancianos y con insuficiencia renal), y no sufre metabolismo hepático por el sistema del citocromo P450, por lo que presenta un perfil de fármaco sin grandes problemas de interacción con otros medicamentos. Rivaroxaban será probablemente el primer fármaco anticoagulante oral inhibidor directo del factor Xa (FXa) disponible. Produce una inhibición reversible y predecible de la actividad del FXa con capacidad de inhibir el FXa ligado al coágulo. Sus características farmacocinéticas incluyen rápida absorción, con elevadas biodisponibilidad y unión a proteínas plasmáticas y semivida de eliminación de, aproximadamente, 8 h. La eliminación es de tipo dual, renal (mayoritaria) y biliar. Aunque ha demostrado tener un potencial moderado de interacción con inhibidores fuertes del citocromo P450-A4, no parece inhibir ni inducir ninguna enzima P450 (AU)

Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme (AU)

Pharmacokinetics of methadone in human-immunodeficiency-virus-infected patients receiving nevirapine once daily.

The effect of nevirapine once-daily dosing on the pharmacokinetics of methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, was evaluated in ten HIV positive patients on stable methadone therapy. Nevirapine 200 mg once daily was administered orally from day 1 to day 14. On day 15, nevirapine dose was increased to 400 mg once daily for the following 7 days of study and thereafter. On days 0, 8, and 22, concentration-time profiles of methadone and its metabolite were collected after methadone intake. Noncompartmental pharmacokinetic analysis was performed. Pharmacokinetic parameters obtained on days 8 and 22 were compared with those obtained before nevirapine administration. After starting nevirapine treatment, nine out of ten patients experienced symptoms of abstinence syndrome, and methadone dose had to be increased by 20% on average during the course of the study. After 7 days with nevirapine 200 mg, methadone area under the plasma concentration time curve (AUC) and maximum concentration (C(max)) values were reduced by 63.3% and 55.2%, respectively. Switching to high dose nevirapine (400 mg once daily) did not result in a greater decrease in the methadone AUC and C(max) compared with 200 mg nevirapine. None of the noncompartmental pharmacokinetic parameters of methadone metabolite evidenced statistically significant differences across the three study periods. The decrease in methadone AUC and C(max) administrated once daily was similar to that seen in other studies with nevirapine administrated twice daily, suggesting that the degree of induction of methadone metabolism by nevirapine is similar for both dosing regimens.

Acute cholestatic hepatitis probably associated with risperidone.

OBJECTIVE: Risperidone is an atypical neuroleptic drug widely used due to the lower incidence and severity of hepatic adverse effects in comparison to phenothiazines. Although idiosyncratic reversible hepatotoxicity may occur in association with risperidone, the interaction with fluoxetine might increase the risk of toxic liver injury in a vulnerable patient. METHODS AND RESULTS: We present a case of acute cholestatic hepatitis probably associated with the use of risperidone after only a few days of therapy in a patient also treated with fluoxetine. The patient, a 64-year-old male, developed a rapid increase in liver enzymes after starting treatment with only four doses of risperidone 2 mg/day. CONCLUSIONS: We recommend obtaining baseline liver function tests before starting risperidone and regular monitoring to screen patients for liver damage during therapy whenever a patient is also receiving fluoxetine.

Neuropatía periférica y óptica asociada a linezolid en un paciente con infección por Mycobacterium bovis multirresistente / Peripheral and optic neuropathy associated to linezolod in multidrug resistant Mycobacterium bovis infection

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Controversias sobre los antagonistas del calcio en el tratamiento de la hipertensión arterial / Controversies about calcium antagonists in the management of high blood pressure

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