The mechanism underlying the increased pharmacological effects of phenobarbital in rats with glycerolinduced acute renal failure (ARF) was examined. In the experiments, a surgical cannula was inserted in the lateral ventricle of the rats for phenobarbital infusion, and the ARF induction was performed by intramuscular administration of 50% glycerol. The onset time of anesthesia by phenobarbital was determined with the tail flick method. In addition, cerebral microsomes were prepared from excised cerebral cortices of sham and ARF rats, and the cerebral expression of the γ-aminobutyric acid (GABA) A receptor and two cation-chloride transporters, KCC2 and NKCC1, was evaluated by Western blotting, as their functions are involved in the anesthetic effects of phenobarbital. When phenobarbital was infused in the ventricle, anesthesia was induced 2.2-times faster in ARF rats than in sham rats, and there was no detectable increase in the cerebral expression of the GABA A receptor in ARF rats. It was additionally noted that the cerebral expression of KCC2 decreased, whereas that of NKCC1 was unaltered in ARF rats. These findings indicated that the anesthetic effects of phenobarbital are potentiated in ARF rats, probably due to imbalanced cerebral expression of KCC2 and NKCC1, suggesting that altered cation-chloride handling in nerve cells is associated.

To clarify whether peripheral inflammation has a remote effect on the central nervous system, the electrolyte disposition between the circulating blood and central nervous system was evaluated in rats with carrageenan-induced acute peripheral inflammation (API). λ-Carrageenan was subcutaneously injected in the hind paw of the rat, and lithium was utilized as a surrogate marker of sodium. When the plasma and cerebrospinal fluid (CSF) concentrations of lithium were examined following lithium being intravenously administered, it was revealed that the CSF concentration of lithium in API rats is reduced compared to that in normal rats, while the plasma concentration profile of lithium in API rats is indistinguishable from that in normal rats. The pharmacokinetic analysis showed that the lithium disposition from the plasma to CSF markedly decreased by 35.8% in API rats compared to that in normal rats. On the other hand, when lithium was immediately administered into the lateral ventricle, its elimination profiles in CSF were not different between normal and API rats. It is therefore probable that the lithium disposition from the plasma to CSF alters in API rats, reflecting the entry process of electrolytes from the circulating blood to brain tissue being suppressed in response to peripheral inflammation.

No abstract

Postpartum rubella vaccination is recommended for puerperal women with low rubella antibody titer to prevent congenital rubella syndrome. We have constructed a protocol-based pharmacotherapy management (PBPM) that contributes to the ef ciency and safety of rubella vaccination, and we report the results. The ward pharmacist identi ed a puerperal woman with low rubella antibody titer, provided drug guidance regarding the rubella vaccine to that person, and requested a doctor to prescribe it. When identifying the subjects, it was con rmed whether or not they were inappropriate for vaccination as described in the package insert of the rubella vaccine. The subjects were puerperal women who gave birth at our hospital from April 1, 2017 to March 30, 2020. The vaccination rate (56.7％) after the introduction of PBPM was not signi cantly different from that when led by a doctor (60.0％). The vaccination avoidance rate for those who were unsuitable for rubella vaccination was 71.4％ (5/7) before the introduction of PBPM, and 100.0％ (9/9) after the introduction of PBPM. Intervening after con rming the package insert is considered to be the work of the pharmacist from the viewpoint of drug management. The introduction of PBPM not only reduces the burden on doctors, but also avoids the health hazards of the rubella vaccine and the inadequate effectiveness of the vaccine, which is considered to be a signi cant initiative.