한국적 의학 기준에 근거한 고혈압환자의 Angiotensin II Receptor Blockers와 Calcium Channel Blockers의 약물 평가

이옥상,천영주,예경남,윤희영,김정태,이윤정,임성실 대한약학회 2014 약학회지 Vol.58 No.2

Oriental lifestyle for treating diseases has been developed and well-accepted for a long time among Koreans. Sasang Constitution theory, originated from Korean traditional medicine, suggests that medication treat-ment should be differentiated by each patient’s body classification (So-yang [SY], So-eum [SE], Tae-yang [TY], and Tae-eum [TE]), in contrary to western medicine’s theory that medication should be applied equally by disease indication without such classification. However, the pharmacotherapeutic outcomes of these theories have not been compared to date. In this study, we aimed to compare the two theories by evaluating blood pressure (BP), which is lowered as a therapeutic outcome, among hypertensive patients taking angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs), two most com-monly used antihypertensive classes in Korea. Methods: From April 2006 to June 2012, we retrospectively collected data on hypertensive patients with Sasang Constitution classification at Kyunghee University Hospital at Gangdong, one of the East-West collaborative medical centers in Korea. We collected information on age, gender, underlying diseases, anti-hypertensive drugs (ARB, CCB, ARB+CCB), and BP by reviewing the electronic medical records. We excluded patients with missing blood pressure at baseline or follow-up, or those who had a change in their antihypertensive drug class during follow-up. Results: We selected a total of 573 patients (SY: 165, SE: 158, TY: 0, TE: 250). Baseline BPs were on average 139.0/82.0 mmHg for SY, 137.8/78.5 mmHg for SE, and 138.7/79.2 mmHg for TE. In all three groups, CCBs were the most prescribed, followed by combination therapy with ARB+CCB, then ARBs. BP reduction after 1 month of initial medication was significantly different among the drug classes, but not in Sasang constitutional classification (ARB [SY: -12.4/-4.7, SE:-12.3/-2.5, TE: -8.6/-1.8], CCB [SY: -12.3/-5.4, SE: -13.0/-2.3, TE: -10.8/-6.0], ARB+CCB [SY: -15.6/-6.7, SE: -18.4/-8.1, TE:-20.2/-6.7], drug [P≤0.05/P>0.05], constitutional type [P>0.05/P>0.05]). Conclusion: We observed significant differences in reduction of blood pressure by classes of drugs (ARB+CCB>CCB>ARB) but not by Sasang constitutional classification. Therefore, current approach of antihypertensive pharmacotherapy assisted by Western medicine is appropriate for treat-ment of hypertension. However, further larger scale or prospective studies are required in order to confirm these results.

β-Adrenergic Receptors : New Target in Breast Cancer

Wang, Ting,Li, Yu,Lu, Hai-Ling,Meng, Qing-Wei,Cai, Li,Chen, Xue-Song Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background: Preclinical studies have demonstrated that ${\beta}$-adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. Materials and Methods: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and beta-adrenoceptor blockers. Results: Ten publications met the inclusion criteria. Six suggested that receiving beta-adrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapse-free survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. Conclusions: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis.

Association Between The Use of Angiotensin Receptor Blockers/ Calcium Channel Blockers and Risk of Interstitial Lung Disease/ Idiopathic Pulmonary Fibrosis: A Nationwide Cohort Study

( Hye Jin Jang ),( Dong Yoon Lee ),( Jin-ho Kim ),( Jihyeon Jeong ),( Won-il Choi ) 대한결핵 및 호흡기학회 2023 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.136 No.0

고혈압 환자에서 칼슘차단제의 부작용에 관한 시판 후 조사

조홍준,최현림,서홍관,양윤준,신호철,김경수,김영주,조경환,이신휘,정승필,이정권,안윤옥,김영식,Cho, Hong-Jun,Choi, Hyun-Rim,Seo, Hong-Gwan,Yang, Yoon-Joon,Shin, Ho-Cheol,Kim, Kyung-Soo,Kim, Young-Joo,Cho, Kyung-Hwan,Lee, Shin-Whee,Jung, Seung- 대한임상약리학회 1994 臨床藥理學會誌 Vol.2 No.2

연구배경 : 칼슘차단제 투여 시 나타나는 각종 부작용의 발생률과 이와 관련된 요인을 밝히고자 칼슘차단제를 투여 받은 고혈압 환자를 대상으로 시판 후 조사를 하였다. 방법 : 1993년 2월부터 1993년 10월까지 칼슘차단제를 투여 받은 고혈압 환자 360명을 연구대상으로 하였다. 연구대상자중 남자가 142명, 여자가 218명이었으며, 연령별로는 50세 미만 103명, $50{\sim}59$세 155명, 60세 이상이 102명 이었다. 약물투여 후 2,4,6,8주에 추적 관찰하였으며, 부작용의 발생률은 Kaplan-Meier 방법과 Log-Rank 방법으로 분석하였다. 결과 : 대상자중 혈관확장과 관련된 부작용의 8주간 누적발생률이 전체적으로 38.9%였으며, 안면홍조 23.3%, 두통 13.5%, 심계항진 13.3%, 현기증 7.6%, 하지부종 6.6% 였다. 이와 같은 부작용들은 발생 후 시간경과에 따라 없어지는 경향이었으며, 최초 발생자중 $6{\sim}12%$에서만 증상이 지속되었다. 안면홍조의 누적발생률은 여자가 29.9%로서 남자의 12.9%보다 높았으며, 하지부종의 경우도 여자가 8.6%로 남자의 3.4%보다 높았다(P<0.05). 안면홍조의 발생률이 여자는 50세미만에서 46.4%로서 $50{\sim}59$세의 21.9%, 60세 이상의 25.9%보다 높았으며, 두통의 발생률도 여자는 50세 미만에서 29.9%로서 $50{\sim}59$세의 12.4%, 60세 이상의 9.3%보다 높았다(P<0.01). 여자에서 Nitrendipine 투여 후 안면홍조의 발생률이 46.1%로 Nitrendipine 투여 후 25.8%(P<0.05), Amlodipine 투여 후 14.3%(P<0.01) 보다 높았으며, 여자에서 Nitrendipine 투여 후 하지부종의 발생률이 18.1%로, Nicardipine의 0.0%보다 높았다(P<0.05). 그 외 부작용으로는 변비 13예, 소화장애 8예, 오심 6예, 잇몸비후, 안면부종, 피로감이 각각 2예, 탈모증, 불면증, 허약감, 피부질환, 호흡곤란, 손발저림, 발한, 구강건조 등이각각 1예 있었다. 칼슘차단제 투여 후 부작용으로 인한 투약 중단율은 10.0% 였다. 결론 : 칼슘차단제 투여 시 혈관확장과 관련된 부작용의 발생률은 39%로 높았으나 시간경과에 따라 점차 없어져서 발생자중 10%정도에서만 증상이 지속되었으며, 안면홍조, 두통, 하지부종의 부작용은 성별, 연령 및 약제에 따라 발생률에 차이가 있었다. Purpose : To estimate the incidence and features of adverse events resulting from the use of calcium channel blockers a multicenter postmarketing surveillance study was carried out. Method : To ascertain adverse events associated with calcium channel blockers usage, we followed regularly the hypertensive patients with the use of calcium channel blockers at the interval of 2,4,6,8 weeks. A total of 360 patients, 17,825 person-days, at 11 clinics were observed from February 1993 to September 1993. The incidence patterns of adverse events were analysed using Kaplan-Meier method. Results : Median follow-up days per person were 54 and the proportion of uncensored cases was 56.7%. Vasodilatory adverse events were observed in 38.9% of the patients during 8 weeks, where flushing, headache, palpitation, dizziness and peripheral edema occurred in 23.3%, 13.5%, 13.3% , 7.6% and 6.6% of the patients, respectively. These declined with time during continued therapy. The incidence of flushing and headache in younger patients(<50 years) were higher than those in older patients(>50 years). The incidence of flushing and peripheral edema associated with use of Niterndipine were higher than those associated with the use of Nicardipine and Amlodipine. The incidence of withdrawal due to adverse events was 10%. Apart from flushing headache, palpitation dizziness and peripheral edema, all other adverse events were constipation, indigestion nausea, gingival hyperplasia, facial edema and fatigue. Conclusion : Vasodilatory adverse events were observed in 38.9% of the patients with the use of calcium channel blockers, which declined with time during continued therapy. Incidences of flushing, headache and peripheral edema were associated with sex, age and the type of calcium channel blocker.

만성 신장병 환자에서 레닌-안지오텐신계 억제제와 칼륨교환수지 동시 사용이 혈청 칼륨에 미치는 영향

이주학 ( Joo Hark Yi ),윤여욱 ( Yeo Wook Yun ),노유석 ( U Seok Noh ),김은영 ( Eun Young Kim ),박재일 ( Jae Il Park ),한상웅 ( Sang Woong Han ),김호중 ( Ho Jung Kim ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.5

Purpose : This prospective study aimed to evaluate the safety and efficacy of potassium-exchange resin (PER, Kalimateⓡ or Argamateⓡ) for managing hyperkalemia induced by Renin-Angiotensin System (RAS) blockers in chronic kidney disease (CKD) patients without their discontinuation. Methods : Besides conservative remedies including low-potassium diet, all hyperkalemic CKD patients (n=21, [K] ≥5.6 mEq/L) received PER added on angiotensin-converting enzyme inhibitor (Moexipril, n=2) or angiotensin-receptor blocker (Irbesartan, n=19) with, at least, weekly monitoring of serum [K] if its level remains more than 5.5 mEq/L for more than 2 months (mean±SD, 6.8±5.9 mon; range, 2-26 mon). Results : Baseline serum [K] on RAS blocker alone (5.1±0.4 mEq/L; 4.2-6.3 mEq/L) increased to 6.0 ±0.4 mEq/L (p<0.05) before adding PER, and then it was significantly decreased to 5.3±0.6 mEq/L at the first clinic visit (p<0.05) and to 5.0±0.7 mEq/L at the last clinic visit (p<0.05) following the administration of PER added on RAS blocker. During the study period, GFR, serum creatinine and urinary protein excretion didn`t change significantly. Conclusion : The development of hyperkalemia on RAS blockers in CKD patients doesn`t necessarily lead to withdrawal of RAS blockers when the cautious add-on therapy of potassium-exchange resin with other conservative remedies launches, unless severe refractory hyperkalemia persists. II type 1 receptor blockers

안지오텐신 변환효소 억제제와 안지오텐신 II 수용체 차단제 투여 후 발생한 급성 신부전과 폐부종으로 전원된 선천성 단일신 환자의 치료 1예

백두현,김경진,홍성철,강석형,송하응,김혜인,김수현,오현정,강혜원,김서우,유민아,류동열,최규복,강덕희 이화여자대학교 의과대학 2010 EMJ (Ewha medical journal) Vol.33 No.1

Blockers of renin-angiotensin system(RAS) including ACE inhibitor or ARB are one of the most frequently prescribed medications for the treatment of hypertension, heart failure and proteinuria. One of the major side effects of these RAS blockers is the deterioration of renal function, mainly due to a reduction of intraglomerular pressure. Therefore, close monitoring of renal function is recommended when RAS blockers are initially prescribed, especially for the patients with impaired renal function. We report a patient who was transferred to our hospital due to the sudden development of oliguria and dyspnea after treatment for hypertension with ACEi and ARB. She was finally diagnosed as RAS blocker-induced acute renal failure with pulmonary edema complicated on congenital solitary kidney. After hemodialysis and conservative treatment, her renal function was recovered with maintenance of normal urine output. Conclusion:This case highlights the necessity of the functional and structural evaluation of kidney to prevent the serious complication such as acute renal failure before the administration of ACEi and/or ARB.

The etiology and possible molecular mechanisms underlying calcium channel blocker-induced gingival enlargement: a narrative review

Seul Lee,유형근 조선대학교 치의학연구원 2022 Oral Biology Research (Oral Biol Res) Vol.46 No.4

Gingival enlargement, defined as the abnormal proliferation of gingival tissue, can be caused by exposure to poor oral hygiene, periodontal diseases, or systemic drugs such as antihypertensive, immunosuppressive, and anticonvulsant agents. Although numerous clinical studies have examined drug-induced gingival enlargement, there is limited evidence on the molecular mechanisms underlying this disease. Therefore, the current study aims to summarize the available literature on the effects of systemic drugs such as antihypertensive agents and calcium channel blockers used for the treatment of cardiac diseases on gingival enlargement expression, and to discuss possible molecular mechanisms underlying drug-induced gingival enlargement.

Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study

김재헌,심성률,장인호,신인수,황성동,김계환,윤상진,송윤섭 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.2

Purpose: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg orother alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis andmeta-regression. Materials and Methods: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate SymptomScore (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzedusing adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980to June 2013. Results: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alphablockers(terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardizedmean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control groupwas 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosingroup versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (numberof patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. Conclusion: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alphablockersas an initial treatment strategy for men with lower urinary tract symptoms.

Possible Liver Injury in Patients Treated with Fimasartan, a Novel Angiotensin II Receptor Blocker: Experience of a Single Tertiary Health Care Center

( Jae-jun Shim ),( Jae Hoon Park ),( Jong Sin Woo ),( Byung-ho Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: We recently experienced two cases with severe hepatotoxicity associated with fimasartan, a novel angiotensin II receptor blocker (ARB) in Korea. We investigated incidence of significant liver injury (SLI) among patients receiving various ARBs in a tertiary health care center. Methods: SLI was defined as increased serum level of alanine aminotransferase (ALT) more than 3-fold of upper limit of normal (male > 90 U/L, female > 57 U/L). The patients who started ARB and had available baseline and follow-up ALT levels were enrolled during 2011 to 2016. Another class of antihypertensive agent, amlodipine was investigated as a control group. Results: A total of 13,122 patients were enrolled. Mean age was 61.3 years and female to male ratio was 50.5:49.5. Mean baseline ALT level was 24.6 U/L. Following ARB treatment, change of ALT level was only found in fimasartan group (24.7 to 34.8 U/L, P<0.001 by paired t-test). The incidence of SLI was 5.4%, 2.1%, 2.1%, and 2.5% in fimasartan (N = 930), candensartan (N = 5,941), valsartan (N = 2,980), and amlodipine group (N = 3,271), respectively (P<0.001). Even after propensity score matching, the incidence of SLI in fimasartan group was significantly higher than the other groups (P< 0.05). In a multivariate Cox proportional hazard model, SLI was independently associated with higher baseline ALT level, female, younger age, and fimasartan use. Severe liver damage (ALT > 200 U/L) was found in 45 patients and most of them were not related to medication. Only 4 patients were clinically related to antihypertensive agent, exclusively fimasartan. Causality assessment grades in those patients were all probable (score: 6-8). Conclusions: Fimasartan might be associated with hepatotoxicity in a small group of patients. A large scale survey to characterize its clinical outcomes and to find high-risk group is needed.

Case Report : Severe Hyponatremia Associated with the Use of Angiotensin II Receptor Blocker/thiazide Combinations

( Da Rae Kim ),( Joo Hee Cho ),( Won Seok Jang ),( Jin Sug Kim ),( Kyung Hwan Jeong ),( Tae Won Lee ),( Chun Gyoo Ihm ) 대한전해질학회 2013 Electrolytes & Blood Pressure Vol.11 No.2

There are several widely used combinations of angiotensin II receptor blocker (ARB)/ thiazide. The complimentary mechanism of action for such antihypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia,even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.