永島 一輝

Pharmacists who provide medication to patients immediately before they overdose should intervene appropriately; however, little information exists on the types and amounts of over-the-counter (OTC) drugs that are dangerous. This study investigated the toxicity and characteristics of overdosing on a single package of commercially available OTC drugs in humans. We researched 14,107 OTC drugs. The number of products that could contain a lethal dose if taken as a single package was 1,223 (8.7%) and a toxic dose was 2,982 (21.1%). A single product containing a lethal dose to humans by therapeutic category included skin drugs (n = 672, 25.0%), psychotropic drugs (n = 288, 17.9%), and public health drugs (n = 92, 26.1%) in descending order. Comparing before and after April 2023, the number of OTC pharmaceuticals that contained ingredients that may be abused, significantly increased: psychotropic drugs (44.9% increase), respiratory drugs (8.2% increase), and urogenital and anal organs drugs (3.5% increase) (p < 0.05). These products had not been previously designated as hazardous despite their potential for abuse. The registrants in the "Drug Database for Overdose Prevention" that made these public included 199 pharmacists, registered sellers, and doctors as of July 31, 2024. The city with the most users was Osaka (377 users) and an average engagement time of 41.8 seconds, followed by Sapporo, Fukuoka, and Nagoya. These areas were consistent with urban centers and high numbers of emergency transports due to overdose. Our findings provide important pharmaceutical information that pharmacists can use for their gatekeeper activities.

薬局への来局者および薬局薬剤師へアンケート調査を行い、両者の副作用への認識の違いについて検討した。来局者アンケートでは210人、薬局薬剤師へのアンケート調査では60人から回答が得られた。副作用と思う状況を選択する質問では、薬剤師アンケートでは「花粉症処方薬で傾眠」を選択した人は55人(91.7%)と多く、「脂質異常症治療薬で肝障害」47人(78.3%)、「漢方薬で肝障害」43人(71.7%)、「通販の薬で体調不良」42人(70.0%)と続いた。来局者アンケートでは「花粉症処方薬で傾眠」を選択した人が110人(52.4%)と多く、次点で「通販の薬で体調不良」55人(26.2%)であった。薬剤師は服用開始/中止のタイミングと症状発現の時間的関係の情報をもとにした薬物動態学的考察や添付文書等の医薬品情報をもとに、来局者は自身の経験や自覚しやすい症状をもとに副作用について認識していることが明らかとなった。

BACKGROUND: During disasters (including epidemics such as coronavirus disease 2019), the capacity of emergency departments is exceeded, thereby hindering the administration of appropriate lifesaving measures. Furthermore, the number of overdose patients increases because of the stress overload during emergency situation. The fact that overdose patients are forced to be transported to medical facilities that do not typically treat them is becoming worrisome. Moreover, there is no definitive score for overdose. This study aimed to create a patient-specific scoring system to assess overdose. METHODS: This was a retrospective single-center study. The evidence-based OD score was evaluated on a scale of 0-15. Further, logistic analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the score. RESULTS: Overall, 262 patients (including 118 overdose patients) receiving care at the intensive care unit of Japan's Teikyo University Hospital in 2021 were targeted. Regarding the total OD score, ROC analysis revealed a cutoff of 8 (area under the curve [AUC]: 0.99, 95% confidence interval [CI]: 0.980-0.997, sensitivity: 0.95, specificity: 0.95, p < 0.05), which was considered to indicate an overdose. Of the items evaluated in the OD score, the scenario at the location of the patient's discovery (adjusted odds ratio [AOR]: 16.8, 95% CI: 5.0-255.9, p = 0.002) and recent experience of mental anxiety (AOR: 55.7, 95% CI: 2.8-5399.5, p = 0.03) significantly predicted an overdose in multivariable logistic regression analysis. External validation revealed that the OD score could also identify overdose in patients treated in a cohort from 2022 (average cutoff: 8.6, average AUC: 1.0, p < 0.0001). CONCLUSIONS: The OD score could accurately assess overdose patients. Medical facilities that do not frequently address overdose patients will benefit from the use of this score.

Overdose has become a global social problem. The Japanese government requires gatekeeper training to detect and prevent indicators of overdose and suicide. However, knowledge of necessary factors for the gatekeeper of overdose (patient intervention) is limited. This study aimed to investigate the characteristics of individuals who experienced intervening persons expected to overdose, and to identify the factors required of gatekeepers. A Google form was used to survey 298 pharmacists and registered sellers in Japan. We searched for factors by logistic analysis. Knowledge of prescription drugs used for overdose was higher among pharmacists than among registered sellers. Conversely, pharmacists and registered sellers had similar knowledge about OTC drugs. Overall multivariate logistic regression analysis revealed countermeasures against overdose at their workplace (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 2.25-7.15, P  <  0.01) and knowledge that overdose is on the rise (OR: 1.93, 95% CI: 1.04-3.69, P  <  0.05) to be significantly associated with intervention experience as a gatekeeper. Countermeasures against overdose at their workplace (OR: 2.40, 95% CI: 1.10-5.25, P  <  0.05) in pharmacists and years of work experience (OR: 1.13, 95% CI: 1.04-1.24, P  <  0.05), countermeasure against overdose at their workplace (OR: 3.43, 95% CI: 1.18-10.0, P  <  0.05), and willingness to participate in study sessions and workshops on overdose (OR: 3.50, 95% CI: 1.51-8.10, P  <  0.05) in registered seller were significantly associated with intervention experience as a gatekeeper. These results are useful evidences for countermeasures and gatekeeper training for overdose at pharmacies and drugstores in the community.

Food-derived peptides have various biological activities. When food proteins are ingested orally, they are digested into peptides by endogenous digestive enzymes and absorbed by the immune cell-rich intestinal tract. However, little is known about the effects of food-derived peptides on the motility of human immune cells. In this study, we aimed to understand the effects of peptides derived from a soybean protein β-conglycinin on the motility of human peripheral polymorphonuclear leukocytes. We illustrated that MITL and MITLAIPVNKPGR, produced by digestion using in-vivo enzymes (trypsin and pancreatic elastase) of β-conglycinin, induces the migration of dibutyryl cAMP (Bt2 cAMP)-differentiated human promyelocytic leukemia 60 (HL-60) cells and human polymorphonuclear leukocytes in a dose- and time-dependent manner. This migration was more pronounced in Bt2 cAMP-differentiated HL-60 cells; mRNA expression of formyl peptide receptor (FPR) 1 increased significantly than in all-trans-retinoic acid (ATRA)-differentiated HL-60 cells. This migration was inhibited by tert-butoxycarbonyl (Boc)-MLP, an inhibitor of FPR, and by pretreatment with pertussis toxin (PTX). However, the effect was weak when treated with WRW4, a selective inhibitor of the FPR2. We then demonstrated that MITLAIPVNKPGR induced intracellular calcium responses in human polymorphonuclear leukocytes and Bt2 cAMP-HL60 cells. Furthermore, pre-treatment by fMLP desensitized the calcium response of MITLAIPVNKPGR in these cells. From the above, MITLAIPVNKPGR and MITL derived from soybean β-conglycinin induced polymorphonuclear leukocyte migration via the FPR1-dependent mechanism. We found chemotactic peptides to human polymorphonuclear leukocytes, which are the endogenous enzyme digests of soybean protein.