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This study assessed the prevalence of the inappropriate use of over-the-counter (OTC) cold medicine among adolescents and examined the relationships between knowledge, literacy, and the inappropria...

Objective This study assessed the prevalence of children's and adolescents' pain experiences and use of medicine and examined the relationships between pain experiences, medication knowledge, literacy, and use of medicine. Method A probability-proportionate-to-size sampling method was used to systematically draw a random sample of schools. In 2014, a national representative sample of 2309 students from 35 primary schools (5th–6th grade), 2700 students from 30 middle schools, and 2013 students from 20 high schools completed the online survey. Results Overall, 85.6% of children and adolescents reported experiencing pain during the past year that included headache (63.0%), throat ache (59.3%), muscle ache (58.3%), stomach pain (42.9%), menstrual pain (girls: 42.1%), and dental pain (38.5%). Children and adolescents had taken cold/cough medicine (48.1%), acetaminophen (15.0%), antacids (14.8%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (10.5%) in the past year. Multivariate analysis results indicated that after controlling for pain experiences children and adolescents who had lower levels of medication knowledge and literacy were more likely to use pain medication and antacids more frequently. In addition, children and adolescents who had lower medication knowledge, lower literacy, asked doctors to prescribe antacids, and co-administered with antacids were more likely to report long-term use of antacids. Conclusions Lower levels of medication knowledge and literacy among children and adolescents were associated with more frequent use of pain medication and antacids.

Long-term continuous exposure to potentially inappropriate medications (PIMs) can lead to adverse events in the elderly. However, the effects of long-term exposure of the elderly to PIM and the relationship between PIM and chronic diseases remain unclear. The objective of this study was to investigate the continuous use of PIMs in a community-dwelling elderly population. A cross-sectional population-based study was conducted using community pharmacy&ndash, filed dispensing records from the Hcare system. Twenty-three community pharmacies were sampled from 2013 to 2015 to obtain records of patients above 65 years-old with continuous prescriptions. PIM were identified according to the 2015 Beers Criteria. The prevalence of patients using PIM was highest in patients with co-morbid mental disorders (40.05%), followed by neurological system disorders (28.91%). Patients who were prescribed a PIM were more than three times as likely to have a mental disorder as those (odds ratio 3.16, 95% confidence interval: 3.06&ndash, 3.28) with non-chronic diseases. The most prescribed PIM agents were central nervous system drugs (53.16%), and benzodiazepines (35.15%). Patients with mental disorders had the highest rate of long-term persistent PIM exposure, with benzodiazepines being the most frequently dispensed. Drug safety concerns should be closely monitored in elderly patients with the abovementioned conditions.

Patients with high healthcare utilization are at increased risk of polypharmacy and drug interactions. This study investigated the changes in the number of medications, drug interactions and interaction severity in high frequency outpatients with polypharmacy at hospitals and clinics in Taiwan after home pharmaceutical care, to understand the effectiveness of interventions by pharmacists. This was a retrospective observational study. Cases with excessive polypharmacy (10+ drugs) were selected from the Pharmaceutical Care Practice System database of the Taiwan Pharmacist Association in 2017. After the home care intervention, the number of drug types used decreased 1.89-fold (p &lt, 0.001), and the number of medications fell 61.6%. The incidence of drug interaction was 93.82%. In an average case, the incidence of drug interaction after the pharmacist intervention decreased 0.6-fold (p &lt, 0.001). The drug most commonly causing interactions was aspirin, followed by diclofenac, also common were three used in diabetes, two psycholeptics and two beta blockers. Among 22 cases of severe drug interaction, seven resulted in increased risk of extrapyramidal symptoms and neuroleptic malignant syndrome. By analyzing the relationship between the side effects of individual drugs and the pharmacokinetic Tmax, a sequential thermal zone model of adverse drug reactions can be established, the value of which could prompt physicians and pharmacists to intervene in order to prevent adverse events. It is concluded that home pharmaceutical care by pharmacists can significantly reduce the number of medications and interactions in patients with excessive polypharmacy and high healthcare utilization.

This study was designed to determine whether genetic differences influence the rewarding effects of nicotine in 4 inbred strains of mice (DBA/2, BALB/c, C3H, and C57BL/6). Nicotine (subcutaneous) induced a place preference in DBA/2 and BALB/c mice but a place aversion in C57BL/6 mice. A low dose of nicotine produced a significant place preference, whereas a high dose of nicotine produced place aversion in C3H mice. These effects were completely reversed by the nicotinic receptor antagonist mecamylamine. These results strongly suggest that a conditioned state, such as rewarding effects or aversive effects, can be influenced by genetic background.

Psychostimulant abuse has been a serious social problem worldwide for a long time. Bupropion, which is used as an antidepressant and to aid smoking cessation in the US, is considered to have psychostimulant-like activity. Although activation of the dopaminergic system induces several behavioral effects and bupropion can activate the dopaminergic system, the abuse potential and other behavioral effects of bupropion have not been fully investigated. Therefore, in this study we compared the behavioral effects of bupropion to those of psychostimulants in mice. Both methamphetamine and bupropion induced sensitization to locomotor activity, and cross-sensitized each other. Methamphetamine and bupropion also induced robust rewarding effects as measured by the conditioned place preference paradigm, although the conditioned reward with bupropion extinguished faster than that with methamphetamine. Furthermore, unlike psychostimulants, bupropion did not disrupt prepulse inhibition, even in bupropion-sensitized mice. These findings constitute evidence that bupropion and methamphetamine have similar pharmacological profiles, particularly with regard to dopamine-related behaviors. However, bupropion has lower abuse potential and side effects than methamphetamine.

Remarkably high regio- and stereoselective approaches for the syntheses of dendrobatid alkaloids (+)-allopumiliotoxin 267A and 339A have been developed. As a model study for the syntheses of these alkaloids, we initially undertook intramolecular chromium(II)-mediated cyclization of the racemic N-(iodoalkenyl)piperidine 8, which smoothly proceeded by treatment with CrCl 2 (5 equiv) and catalytic NiCl 2 (2.5 mol%) in DMF to form a 1.3:1 epimeric mixture of 2-hydroxy-3(E)-alkylidene-trans-quinolizidines 33a and 33b. When the alternative chiral N-(iodoalkenyl)piperidine 9 was subjected to the identical cyclization conditions, the 3(E)-alkylidene-trans-quinolizidine 35a with the axially oriented 2-hydroxy group was formed as a single isomer. Based on these model studies, we then undertook the enantioselectivie total synthesis of (+)-allopumiliotoxin 267A (1). For the synthesis of (1), coupling of the two segments, (E)-vinyl iodide 45, obtained via stereospecific palladium-catalyzed hydrostannation, and the pyrrolidine derivative 54, gave the N-(iodoalkenyl)pyrrolidine 56, which underwent intramolecular chromium-(II)-mediated cyclization, exclusively providing 58 with complete retention of the required (E)-alkenyl geometry. Subsequent cleavage of the benzyl group furnished 1. Synthesis of allopumiliotoxin 339A (2) was next investigated bu employing the strategy developed for 1. The side-chain segment, (E)-vinyl iodide 74, was prepared via high-degree stereo- and regioselective reactions involving Evans alkylation and palladium-catalyzed hydrostannation. Intramolecular nickel (II)/chromium(II)-mediated cyclization of the N-(iodoalkenyl)pyrrolidine 82, available via coupling 74 with pyrrolidine derivative 79, led to exclusive formation of 83, which was deprotected to afford 2

The key precursor for the preparation of 1β-methylcarbapenem antibiotic was stereoselectively synthesized from (+)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone by employing an intermolecular carbenoid displacement reaction as a key step.

An alternative asymmetric synthesis of (+)-(lS,9aS)-homopumiliotoxin 223G (1) was accomplished via (1R,2R, 9aS)-1-(benzyloxy)-2-hydroxy-1-methyl-3[(E)-isobutylidene]++ +quinolizidi ne (4), which was synthesized according to the intramolecular nickel(II)/chromium(II)-mediated cyclization of the N-(iodoalkenyl)aldehyde 2. Compound 4 was converted to the acetate and subjected to reduction with lithium in ammonia, whereupon deprotection of the O-benzyl group and removal of the acetoxyl group occurred in a single operation to afford (+)-homopumiliotoxin 223G. The same sequence using (+/-)-4 was applied to the synthesis of racemic 223G. Gas chromatography of a sample of racemic 223G showed no separation into enantiomers on four different cyclodextrin-based chiral GC columns. We found, however, that the O-acetates of (+/-)-223G gave a nearly baseline separation on either a beta-cyclodextrin column or a permethylated beta-cyclodextrin column. The O-acetate of synthetic (+)-223G was identical on either of these two columns, with the first eluting O-acetate from acetylated (+/-)-223G and also with the acetylated 223G present in a frog skin extract, thus allowing us to confirm unambiguously the 1S,9aS absolute configurations of natural 223G.

A novel construction of penem and carbapenem ring systems has been achieved by employing an oxalimide cyclization as a key step.