Projecting supply and demand for pharmacists in pharmacies based on the number of prescriptions and system dynamics modeling.

BACKGROUND: Pharmacists play an important role in promoting people's health in Japan, which has an aging population. Hence, it is necessary that the distribution of pharmacists meets the population's needs in each region. This study projects the future supply and demand for pharmacists in pharmacies to consider an optimal distribution of pharmacists. METHODS: The future supply of pharmacists working in pharmacies in Hokkaido is projected using system dynamics modeling, according to their career path. The demand is projected based on the number of prescriptions, sourced from publicly available sources. The analysis period is 2015-2040. The estimated demand is converted into the number of pharmacists and the sufficiency is evaluated using sufficiency ratio (supply/demand ratio). Sensitivity analyses of the sufficiency ratio were conducted to estimate the effects of changes in parameters such as national exam pass rate, enrollments, attrition rates, the number of prescriptions per pharmacist, and diffusion of newly licensed pharmacists. RESULTS: The projected supply, in 2025 and 2040, is 1.24 and 1.56 times, respectively, as that in 2015 and the demand is 1.11 and 0.98 times, respectively. In 2015, although the sufficiency ratio in Hokkaido overall is 1.19, the ratios are higher in urban medical areas and lower than 1 in rural medical areas, such as Minamihiyama, Emmon, and Nemuro. By 2040, the sufficiency ratios are greater than 1 for all areas except for Emmon and higher than 2 in some areas. The sensitivity analyses found that the sufficiency ratio was most sensitive to diffusion of newly licensed pharmacists and the number of prescriptions per pharmacist. CONCLUSION: Optimal distribution should be considered, as the results reveal a possible shortage in the number of pharmacists in rural medical areas in 2015-2025. Conversely, as the demand is projected to decrease after 2025 with a population decrease, future supply should be determined in order not to cause an oversupply after 2025. Refinements of the projection model should be conducted since the related factors such as the roles of pharmacists will change over time.

The Vision and Challenges of Hokkaido Pharmaceutical University's Affiliated Pharmacy.

Hokkaido Pharmaceutical University (HPU), according to its educational mission, seeks to "develop medical professionals who contribute to community medicine", and it has produced more than 6300 graduates since 1974. With recent medical advancements and a progressively aging society, the role of the pharmacist in community medicine has diversified and is increasing in importance. Therefore, in April 2012, the Hokkaido Pharmaceutical University Affiliated Pharmacy was established as a for-profit business of the Educational Foundation of the Hokkaido University of Science, the parent body of HPU. The pharmacy is located near the Sapporo station; it is operated by six pharmacists and four clerks, and supported by three faculty members who are engaged in providing HPU student education such as on-site clinical training, in addition to their pharmacy duties such as home care pharmaceutics. For the first two years it was open, the pharmacy focused on the establishment of pharmacy administration and fiscal consolidation. In April 2015, the Pharmacy Management Committee set the pharmacy's future vision, as well as its mid-term strategy, which consists of the four main components of pharmacy practices, education, research, and social contribution, in order for the pharmacy to serve as a model of community pharmacy.

Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice.

The effects of various protease inhibitors on naloxone-precipitated withdrawal jumping were examined in morphine-dependent mice. The doses of morphine were subcutaneously given twice daily for 2 days (day 1, 30 mg/kg; day 2, 60 mg/kg). On day 3, naloxone (8 mg/kg) was intraperitoneally administered 3h after final injection of morphine (60 mg/kg), and the number of jumping was immediately recorded for 20 min. Naloxone-precipitated withdrawal jumping was significantly suppressed by the intracerebroventricular administration of N-ethylmaleimide (0.5 nmol) and Boc-Tyr-Gly-NHO-Bz (0.4 nmol), inhibitors of cysteine proteases involved in dynorphin degradation, 5 min before each morphine treatment during the induction phase, with none given on the test day, as well as by dynorphin A (62.5 pmol) and dynorphin B (250 pmol). However, amastatin, an aminopeptidase inhibitor, phosphoramidon, an endopeptidase 24.11 inhibitor, and captopril, an angiotensin-converting enzyme inhibitor, caused no changes. The present results suggest that cysteine protease inhibitors suppress naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of dynorphin degradation.

Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems.

RATIONALE AND OBJECTIVES: It is well-known that amphetamine induces increased locomotor activity in rodents. We previously found that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA), an amphetamine metabolite, increases synaptic dopamine (DA) levels in the striatum. In the present study, we investigated the effect of p-OHA on locomotor activity in rodents. RESULTS: In mice, i.c.v. administration of p-OHA significantly increased locomotor activity in a dose-dependent manner. p-Hydroxynorephedrine, another amphetamine metabolite, did not increase locomotor activity. This effect of p-OHA was inhibited by pretreatment with nomifensine, a dopamine-uptake inhibitor, but not by fluoxetine, a serotonin-uptake inhibitor, or diethyldithiocarbamate, a dopamine-beta-hydroxylase inhibitor. Furthermore, we tested the effects of microinjections of p-OHA into the rat nucleus accumbens (NAc) on locomotor activity. Local infusion of p-OHA into the NAc significantly increased locomotor activity. As in mice, the increased locomotor activity induced by p-OHA microinjection into the NAc in rats was inhibited by nomifensine. CONCLUSIONS: These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents.

Cysteine protease inhibitors suppress the development of tolerance to morphine antinociception.

The effects of various protease inhibitors on the development of antinociceptive tolerance to morphine were examined in mice. Intrathecal (i.t.) administration of morphine (0.01-1 nmol) produced a dose-dependent and significant antinociceptive effect in the 0.5% formalin test. When the doses of morphine (mg/kg, s.c. per injection) were given as pretreatment twice daily for two days [first day (30) and second day (60)], i.t. administration of morphine (0.1 nmol) was inactive due to antinociceptive tolerance on the third day. Tolerance to i.t. morphine was significantly suppressed by the i.t. injection of N-ethylmaleimide or Boc-Tyr-Gly-NHO-Bz, inhibitors of cysteine proteases involved in dynorphin degradation, as well as by dynorphin A, dynorphin B and (-) U-50,488, a selective kappa-opioid receptor agonist. On the other hand, amastatin, an aminopeptidase inhibitor, phosphoramidon, an endopeptidase 24.11 inhibitor, lisinopril, an angiotensin-converting enzyme inhibitor, and phenylmethanesulfonyl fluoride, a serine protease inhibitor, were inactive. These results suggest that cysteine protease inhibitors suppress the development of morphine tolerance presumably through the inhibition of dynorphin degradation.

Intrathecally administered D-cycloserine produces nociceptive behavior through the activation of N-methyl-D-aspartate receptor ion-channel complex acting on the glycine recognition site.

Intrathecal (i.t.) administration of D-cycloserine (100 and 300 fmol), a partial agonist of the glycine recognition site on the N-methyl-D-aspartate (NMDA) receptor ion-channel complex, produced a behavioral response mainly consisting of biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank in mice, which peaked at 5 - 10 min and almost disappeared at 15 min after the injection. The behavior induced by D-cycloserine (300 fmol) was dose-dependently inhibited by an intraperitoneal injection of morphine (0.5-2 mg/kg), suggesting that the behavioral response is related to nociception. The nociceptive behavior was also dose-dependently inhibited by i.t. co-administration of 7-chlorokynurenic acid (0.25-4 nmol), a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex; D-(-)-2-amino-5-phosphonovaleric acid (62.5-500 pmol), a competitive NMDA receptor antagonist; MK-801 (62.5-500 pmol), an NMDA ion-channel blocker; ifenprodil (0.5-8 nmol); arcaine (31-125 pmol); and agmatine (0.1-10 pmol), all being antagonists of the polyamine recognition site on the NMDA receptor ion-channel complex. However, [D-Phe7,D-His9]-substance P(6-11), a specific antagonist for substance P (NK1) receptors, and MEN-10,376, a tachykinin NK2-receptor antagonist, had no effect on D-cycloserine-induced nociceptive behavior. These results in the mouse spinal cord suggest that D-cycloserine-induced nociceptive behavior is mediated through the activation of the NMDA receptor ion-channel complex by acting on the glycine recognition site and that it does not involve the tachykinin receptor mechanism.

Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors.

Intrathecal injection of histamine elicited a behavioral response consisting of scratching, biting and licking in conscious mice. Here, we have examined the involvement of substance P (SP) by using intrathecal injection of tachykinin neurokinin (NK)(1) receptor antagonists and SP antiserum. Histamine-induced behavioral response was evoked significantly 5-10 min after intrathecal injection and reached a maximum at 10-15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 200 to 3200 pmol, and maximum effect was observed at 800-1000 pmol. The H(1) receptor antagonist, d-chlorpheniramine and pyrilamine but not the H(2) receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK(1) receptor antagonists, CP-99,994, RP-67580 and sendide, inhibited histamine-induced behavioral response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK(2) receptor antagonist, MEN-10376, had no effect on the response elicited by histamine. Pretreatment with SP antiserum resulted in a significant reduction of the response to histamine. No significant reduction of histamine-induced response was detected in mice pretreated with NK A antiserum. The present results suggest that elicitation of scratching, biting and licking behavior induced by intrathecal injection of histamine may be largely mediated by NK(1) receptors via H(1) receptors in the spinal cord.