Safety of 2-hour IIVs of tacrolimus in the HSCT unit

Pharmacy residents have the opportunity to complete a research project during their residency training, which provides them with skills on how to conduct and manage a research project. Projects often represent an area of interest and need that has been recognized by the host institution’s pharmacy department. Projects are presented as a poster at an annual CSHP Ontario Branch Residency Research Night, and many eventually go on to be published in a peer-reviewed journal.Background: Administering intravenous (IV) tacrolimus by 24-hour continuous IV infusion (CIV), as recommended by the product monograph, poses significant logistical challenges in the allogeneic hematopoietic stem cell transplantation (HSCT) unit because it requires a dedicated central venous catheter lumen. Consequently, at our institution, tacrolimus has been administered via two-hour intermittent IV infusions (IIV) every twelve hours in the HSCT unit. Administration by IIV is not the standard of practice and shorter infusion times are cautioned due to higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions (IRRs), although there is a paucity of data to support this claim. The primary objective of this retrospective study was to evaluate the safety of a two-hour IIV of tacrolimus in an adult HSCT population. Efficacy was evaluated as a secondary endpoint. Methods and Patients: We performed a retrospective chart review of all patients who received IV tacrolimus at our institution from January 2002 – January 2016. We reviewed 104 patients who received 118 tacrolimus treatment courses by IIV (TTC) [median number of doses per TTC=22, range 1 – 158, interquartile range (IQR) = 28]. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and IRRs that occurred during TTC. The incidence of acute graft-versus-host disease (aGVHD) and disease relapse within 180 days of transplant were collected to evaluate efficacy. Results and Discussion: There were sixteen incidences (13.6%) of nephrotoxicity, defined as a doubling of serum creatinine from baseline. Nephrotoxicity resolved in all but six (5.1%) cases. Precipitating factor for nephrotoxicity unrelated to tacrolimus were identified by the physician in all six cases. There were 40 incidences (34.5%) of neurotoxicity [seizure, posterior reversible encephalopathy syndrome (PRES), tremor, paresthesia, visual disturbance], of which, eight (6.8%) were considered serious (seizure and/or PRES). All neurotoxicity reverted to baseline or resolved completely. One grade 2 infusion reaction occurred and resolved without discontinuation of tacrolimus. In the subset of patients who received tacrolimus for the prevention of aGVHD (n=41), seven patients (17.1%) developed grade II – IV aGVHD. Nine patients (8.7%) experienced relapse of their disease. Conclusions: We propose that a two-hour IIV of tacrolimus is a safe method of administration in the adult HSCT setting. Additional safety and efficacy data from other institutions will provide external validity to this conclusion

Electrophysiological effects of ethanol on monoaminergic neurons: An in vivo and in vitro study

Monoaminergic neurons have been shown to play a role in both the intoxicating and chronic effects of ethanol. We present here the results of a study about the acute effects of ethanol on serotonergic raphe nucleus, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area. These nuclei were investigated electrophysiologically by recording the spontaneous firing rate of single neurons using glass microelectrodes, both in vivo in chloral hydrate anesthetized rats and in vitro in brain slices. Ethanol was perfused intravenously at a rate ranging from 0.2 mg/kg/min to 0.2 g/kg/min in vivo, and at concentrations between 10-8 M and 1 M in vitro. We observed that each monoaminergic nucleus had its own pattern of responses to acute ethanol perfusion, and that high and low concentrations have different actions, suggesting a biphasic effect. For example, in slices, ethanol concentrations higher than 10 mM induce an excitation in most raphe and ventral tegmental area neurons, and an inhibition of firing in locus coeruleus neurons. The results were comparable in the in vivo model, but much more heterogenous. We conclude that the effect of ethanol on the monoaminergic neurons is specific of the type of neuron, and that a biphasic effect is commonly found.SCOPUS: cp.jFLWNAinfo:eu-repo/semantics/publishe