Causative Drugs of Drug-Induced Cough: Analysis of Real-world Data from the Korea Adverse Events Reporting System (KAERS)

( Joonkyung Kim ),( Jee Yea Choi ),( Min Ju Jo ),( Sung Jun Chung ),( Yoomi Yeo ),( Hyun Lee ),( Tai Sun Park ),( Dong Won Park ),( Ji-yong Moon ),( Sang-heon Kim ),( Tae-hyung Kim ),( Jang Won Sohn ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Background Cough is frequently caused by drugs. However, little is known about the epidemiology and causative drugs leading to cough. We analyzed causative drugs and clinical features of drug-induced cough based on 10-year real-world data. Methods We used the database of the Korea Adverse Events Reporting System (KAERS) from January 2009 to December 2018. Cases of drug-induced cough were identified by selecting cases with a cough code of WHO-Adverse Response Terminology without any other adverse events. Causative drugs were compared between acute (<3 weeks) and delayed onset (≥3 weeks). Results In the study period of 10 years, there were 3,021 cases of drug-induced cough. Cough was most frequently caused by cardiovascular drugs (43.8%), followed by respiratory system drugs (14.9 %), including angiotensin-converting enzyme (ACE) inhibitors, antineoplastic and immune-modulating drugs (14.4 %), and anti-infective drug (8.3 %). In acute onset cough, perindopril, docetaxel, ramipril, paclitaxel, and acetylcysteine were found to be frequent causes, while delayed onset cough was commonly caused by perindopril, ramipril, indacaterol, captopril, and imidapril. Conclusion In this analysis of real-world data from a nationwide spontaneous reporting system, various drugs were found to cause cough, while cardiovascular drugs including ACE inhibitors were the most common cause. [This study was funded by the Korea Ministry of Environment (MOE) as ‘‘the Environmental Health Action Program (2016001360003)" and a research grant from the Korea Institute of Drug Safety & Risk Management].

약물 상호작용 모니터링 프로그램의 임상적 유용성 평가

손기호 한국병원약사회 2015 病院藥師會誌 Vol.32 No.4

Polypharmacy (multiple drug use) is considered one of the major risk factors in drugdrug interactions and is a common problem among the elderly patients. It can lead to noncompliance or even discontinuation of the therapy. The purpose of this study was to assess the clinical usefulness, the prevalence, and severity of drug-drug interaction induced ADR (adverse drug reaction) in a long-term care hospital. A retrospective, observational review of electronic medical records and pharmacist interviews with patients were performed. The dataset was analyzed for ADR causality, ADR severity, patient demographic profiles and ADR related characteristics. 324 patients were included (156 males, 168 females), if they were prescribed medication with potential drug-drug interactions, between 1 January 2014 and 31 December 2014 (12 months total). Most patients (80%) were above 65 years old. The patients had a total of 1,680 drugs (average 5.2 drugs per patient), and 932 potential drug-drug interactions (average 2.89 per patient). The most common clinicaly useful ADRs were 17 peptic ulcer and a myopathy. These ADRs were in patients over 65 years age. This indicates the need for rigid ADR monitoring to ensure safety for long-term care patients.

약물군-약물군 조합으로 도출한 약력학적 기전의 추가 병용금기성분

제남경,김동숙,김주연,이숙향 한국임상약학회 2015 한국임상약학회지 Vol.25 No.2

Objectives: Drug utilization review program in Korea has provided ‘drug combinations to avoid (DCA)’ alerts to physicians and pharmacists to prevent potential adverse drug events or inappropriate drug use. Seven hundred and six DCA pairs have been announced officially by the Ministry of Food and Drug Safety (MFDS) by March, 2015. Some DCA pairs could be grouped based on the drug interaction mechanism and its consequences. This study aimed to investigate the drug-drug interaction (DDI) pairs, which may be potential DCAs, generated by the drug class-drug class interaction method. Methods: Eleven additive/synergistic and one antagonistic drug class-drug class interaction groups were identified. By combining drugs of two interacting drug class groups, numerous DDI pairs were made. The status and severity of DDI pairs were examined using Lexicomp and Micromedex. Also, the DCA listing rate was calculated. Results: Among 258 DDI pairs generated by the drug class-drug class interaction method, only 142 pairs were identified as official DCA pairs by the MFDS. One hundred and four pairs were identified as potential DCA pairs to be listed. QT prolonging agents-QT prolonging agents, triptans-ergot alkaloids, tricyclic antidepressants-monoamine oxidase inhibitors, and dopamine agonists-dopamine antagonists were identified as drug class-drug class interaction groups which have less than 50 % DCA listing rate. Conclusion: To improve the clinicians’ adaptability to DCA alerts, the list of DCA pairs needs to be continuously updated.

The Role of In Vitro Detection of Drug- Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions

Klaewsongkram Jettanong,Buranapraditkun Supranee,Thantiworasit Pattarawat,Rerknimitr Pawinee,Tuchinda Papapit,Chularojanamontri Leena,Rerkpattanapipat Ticha,Chanprapaph Kumutnart,Disphanurat Wareeporn 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.6

Propose: The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). Methods: Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. Results: Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of druginduced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of druginduced IFN-γ releasing cells. Conclusion: The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide.

20세기 전환기 미국의 중독성 약물 통제에 드러난 인종 인식— 1914년 해리슨 마약법(Harrison Narcotics Act of 1914)에 대한 재고 —

오영인 수선사학회 2024 史林 Vol.- No.89

. In the United States, it was not President Richard Nixon's War on Drugs that declared drugs a public enemy and began managing them with double standards. This can be traced back to the Harrison Narcotics Act of 1914, 110 years ago, more than half a century before the declaration of war on drugs. According to the Harrison Act, anyone involved in the production, distribution, or sale of narcotic drugs, including opium and cocaine, must register with the National Tax Service and impose taxes in the form of revenue stamps to control the drug distribution network and impose legal sanctions on unregistered illegal distribution. It is the first punitive federal drug law, imposing penalties, in the United States. However, the Harrison Act of 1914 did not receive proper attention in historical studies and was rarely introduced domestically. Even in studies on U.S. drug policy in the fields of sociology, criminology, or medicolegal, the 1914 Act is only briefly mentioned as a piece of precedent history while explaining the war on drugs carried out by the Nixon administration. Therefore, this paper seeks to reexamine the starting point of U.S. drug policy at the turn of the 20th century through the cultural frame of American racial perception at the time. In other words, we will examine how racial prejudice shaped Americans' awareness of the drug problem and how politics utilized this social atmosphere and culture. To do so, we will first look at what the reality of habitual drug use was in the United States in the 19th century and what backgrounds led to criminalize addictive drug use. Next, it will explain what exactly the Harrison Act of 1914 was and for what purpose it was enacted and for whom. Through this study, we would like to reflect on who drug control was for and what it meant in the United States at the turbulent turn of the 20th century.

충북지역 노인들의 약물복용 및 영양상태 -IV. 약물복용 및 건강관련 습관(음주, 흡연, 운동)에 따른 영양상태의 차이-

한경희,김기남,박동연 대한지역사회영양학회 1998 대한지역사회영양학회지 Vol.3 No.3

The purposes of this study were to investigate the effects of drug use & the health-related habits(alcohol drinking, smoking and exercise) on the nutritional status of elderly. subjects were 362 free-living elderly aged over 65(male 131, female 231) in Chungbuk area. Interviews with questionaire on drug use, health-related habits, and nutrient intakes, anthropometric measurement and biochemical blood test were carried out from August to October in 1996. Energy intakes of the males who used drug were lower than those of males who did not use any drug, while energy intakes of the females who used drug were higher than those of females who did not. In biochemical indices, LDL-cholesterol level of the males who used drug was higher than that of males who did not have drug. serum triglycerides, VLDL-cholesterol and obesity degree(BMI & TS) of the females who used drug were higher than those of females who did not have drug. Alcohol drinking, smoking and exercise habits of the elderly who used drug had little effects on the nutrient intakes while those habits had considerable effects on biochemical indices and obesity degree. Among drug users, male drinkers showed higher triglycerides & HDL-cholesterol level, and female drinkers showed higher triglycerides and lower total cholesterol and LDL-cholesterol level, compared to non drinkers. Among female drug users, smokers showed lower body mass index(BMI) compared to non smokers. Males and females who had both drinking and smoking habits showed higher serum triglycerides and VLDL-cholesterol level. Especially females who had both drinking and smoking habits showed lower BMI & Tricep skinfold thickness compared to those who had netiher drinking nor smoking habits.

병용금기와 의약품 사용평가

박지영,박건우 대한의사협회 2012 대한의사협회지 Vol.55 No.5

A drug interaction can be defined as an interaction between a drug and other drugs that prevent the drug from performing as expected. These processes may include alterations in the pharmacokinetics of the drug, such as modulations in the absorption, distribution, metabolism, and elimination (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic characteristics of the drug: the concomitant medication of a receptor antagonist and an agonist for the same receptor. The following interaction may increase or decrease the effectiveness of the drugs or the adverse drug reactions of the drugs. The possibilities of drug interactions should increase as the number of drugs being taken increases in patients. Therefore, patients taking several drugs simultaneously are at the greatest risk for interactions. Drug interactions can contribute to the increasing cost of healthcare because of the costs of medical care that are required to treat problems caused by changes in effectiveness or adverse drug reactions. The drug utilization review (DUR)system has been defined as a structured, ongoing initiative that interprets patterns of drug usage in relation to predetermined criteria and attempts to prevent or minimize inappropriate prescribing. The primary objectives of DUR are to improve the quality of health care for healthcare members and to assist in containing health care costs. In order to achieve these goals, prescription claims must be reviewed both prospectively and retrospectively. The DUR system supplies information to prohibit co-dispensing of contraindicated drugs which increases the risk of drug interactions properly to all the healthcare professionals participating in the care of the patients. In this article, we suggest the importance of DUR in relation to the contraindication of co-medication drugs.

Drug-eluting Microneedles Embedded with Nanoparticles for Anti-inflammatory Purposes

김동민,백승호,고안나,박희경,마용은,이동현 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.4

Microneedle (MN) technology is used to deliver drugs transdermally in a minimally invasive manner with self-administered properties to enable controlled drug release. MNs can improve drug permeation efficiency into the skin by creating tiny holes through which the drugs can directly pass through the stratum corneum, which is the largest barrier layer of the skin. MNs can be used to deliver drugs transdermally by avoiding the gastrointestinal tract route when administering anti-inflammatory drugs so as to avoid damage to the mucous membrane, which can cause gastrointestinal disorders. Dissolving microneedles (DMNs) in biodegradable polymers allows quick dissolution after skin penetration; this can prevent side effects, such as skin irritation due to leftover MN debris on the skin. However, the drugs may be nonspecifically delivered after being released from the MNs, which may reduce their efficacy. Nanoparticles are widely used as drug-delivery systems because they prevent unintentional drug leakage and can specifically deliver drugs through modifications on the nanoparticle surfaces. When such nanoparticles are applied to MNs, the drug release can be controlled and local administration through the skin is possible, making drug delivery more effective. In this review, we describe the materials and manufacturing methods of DMNs as well as recent trends in drug-delivery research using nanoparticleembedded DMNs to control release of anti-inflammatory drugs.

마약범죄의 한계와 효율적 통제를 위한 제언

김대권 한국치안행정학회 2023 한국치안행정논집 Vol.20 No.2

As drug crimes become a very serious problem all over the world, various measures are suggested to analyze the cause and solve the problem. Drug abuse-related problems are currently considered not just a personal matter, but a national issue. Drug crimes therefore have varying definitions such as international crime, victimless crime, etc. and punishment is perceived differently depending on each country's social and cultural background. Drug crimes are attributed to direct or indirect causes including an individual attempt to escape from reality, intended abuse by criminal groups, crimes committed by drug addicts to buy expensive drugs, and secondary crimes committed in drug-induced hallucinations. Transnational drug crimes threaten the country's economic activity and national security, so it is required to recognize the seriousness of drug crimes at national and society levels. Accordingly, comprehensive countermeasures need to be developed by establishing related criminal policies, laws, and institutions. This study tried to understand the current situation centering on the general characteristics of drug crimes and to identify the reality centering on the characteristics of drug users and drug supply and distribution. This study also determined the causes based on criminological evidence to point out the limitations of drug crimes and proposed implications for policies to control drug crimes. 전 세계적으로 마약범죄의 심각성이 확대되면서 이에 대한 원인을 분석하고 문제를 해결하고자 다양한 대책들이 제시되고 있다. 특히 약물남용으로 인한 문제는 개인의 문제를 넘어 국가적 문제로 다루어지고 있다. 마약범죄는 국제성 범죄, 피해자 없는 범죄 등 다양한 형태로 규정되고 처벌도 각국의 사회·문화적 배경에 따라 다르게 인식되어 진다. 마약범죄는 현실을 도피하고 싶은 개인의 문제, 조직범죄자들에 의한 의도적인 중독, 값비싼 마약을 구입하기 위한 약물중독자의 또다른 범죄, 마약 사용 후 환각상태에서의 2차 범죄 등 직·간접적인 원인으로도 범죄가 발생되고 있다. 초국가적 마약범죄는 해당 국가의 경제활동을 위협하고 국가의 안보를 침해하므로 국가적·사회적 차원에서도 마약범죄의 심각성을 인식하여야 한다. 이에 따른 포괄적인 형사 정책적 · 법적 · 제도적 대응책도 신속하게 수행되어야 할 것이다. 이 연구에서는 마약범죄의 일반적 특징을 중심으로 현황을 파악하고, 마약의 사용자와 공급·유통의 특징을 중심으로 실태를 파악하였다. 또한 범죄학적 근거를 바탕으로 원인을 파악하여 마약범죄의 한계를 지적하고 이에 대한 논의를 중심으로 마약범죄 통제정책의 시사점을 도출하였다.

신종마약류 범죄의 특징에 따른 제도적 대응방안 연구

염건웅 한국법학회 2019 법학연구 Vol.76 No.-

In order to study the institutional countermeasures according to the characteristics of new drug crimes, this study identifies the characteristics and status of traditional drug types and new drug types and compares the current status of overseas responses such as the United States, EU, and U.K. and domestic responses. The emergence of the dark Web, social networking services, bitcoin and new drugs has led to Korea being removed from its status as a drug purveyor at a time when the age range of first-time drug users is decreasing to those in their teens and 20s, and ordinary-looking people such as office workers and students become drug-related criminals. To cope with these new drugs, therefore, transnational institutions with a unified one-stop system, such as the U.S. Presidential Committee on Drug Control (PCCN) and the National Organization for Drug Control (ONDCP), should be introduced in the country to help integrate the current system of crackdowns divided into police, prosecution, maritime police and customs offices. In addition, the government should analyze the characteristics of new drug crimes to refine the criteria for punishment for temporary drugs and seek legislative measures to punish the inhalation of unspecified hallucinogenic substances. Drug crimes have the characteristic that they cannot distinguish between perpetrators and victims. This means that drug dealers can make financial gains and buyers can experience pleasure with drugs, so there is nothing to lose from each other. Because of the nature of these drug crimes, such close-knit trading relationships will inevitably last unless they are caught in the investigative network. In particular, since narcotics are addictive drugs, even if they are subject to legal punishment, they often fall back into narcotics after returning to society. In the end, the launch of a one-stop integration agency that can manage the entire drug supply is seen as essential, given that rehabilitation and ongoing management of drug crimes is crucial. 본 연구는 신종마약류 범죄의 특징에 따른 제도적 대응방안을 연구하기 위해 전통적인 마약류의 종류와 신종마약류의 특징과 현황을 파악하고 미국, EU, 영국 등 해외의 대응 현황과 국내의 대응 현황을 비교한다. 마약류을 처음 접하는 연령대가 10대~20대로 낮아지고 있고 사무직과 학생 등 평범해 보이는 사람이 마약류 관련사범이 되는 현실에서 다크웹과 SNS, 비트코인과 신종마약류의 등장은, 결국 한국을 마약청정국 지위에서 내려오게 만들었다. 따라서 이러한 신종마약류에 대처하기 위해서는 미국의 마약퇴치대통령위원회(PCCN)와 국가마약통제정책기구(ONDCP)와 같은 일원화된 원스톱(One-Stop)시스템을 갖춘 초국가적 기관을 국내에도 도입하여 현재 경찰, 검찰, 해양경찰청, 관세청 등으로 나누어져 있는 단속 기관의 시스템을 통합할 수 있는 계기를 마련해야 한다. 또한 신종마약류 범죄의 특성을 분석하여 임시마약류에 대한 처벌기준을 세분화하고 지정되지 않은 환각물질의 흡입 등에 대해서도 처벌할 수 있는 입법방안을 모색해야 한다. 마약류 범죄는 가해자와 피해자를 구분할 수 없다는 특성이 있다. 마약류 판매자는 금전적 이득을 취할 수 있고 구매자는 약물로 쾌락을 경험할 수 있으니 서로에게 손해 볼 것이 없다는 의미이다. 이런 마약류 범죄의 특성 때문에 수사망에 걸리지 않는 한 이와 같은 친밀한 거래 관계는 지속될 수밖에 없다. 특히 마약류는 중독성 약물이기 때문에 법적 처벌을 받는다 해도 사회로 복귀한 이후 다시 마약류에 빠지는 경우가 많다. 결국 마약사범에 대해 치료재활과 지속적인 관리가 중요하게 요구된다는 점에서 마약류 전반을 관리할 수 있는 원스톱 통합기관의 출범은 반드시 필요하다고 보여지는 대목이다.