• 대한임상독성학회지
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• 제16권2호
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• pp.165-171
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• 2018

An overdose of antihypertensive agents, such calcium channel blockers (CCBs) and angiotensin II receptor blocker (ARBs), and the antihyperglycemic agent, metformin, leads to hypotension and lactic acidosis, respectively. A 40-year-old hypertensive and diabetic man with hyperlipidemia and a weight of 110 kg presented to the emergency room with vomiting, dizziness, and hypotension following an attempted drug overdose suicide with combined CCBs, ARBs, 3-hydroxy-3-methylglutaryl-coemzyme A reductase inhibitors, and metformins. A conventional medical treatment initially administered proved ineffective. The treatment was then changed to simultaneous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), which was effective. This shows that simultaneous ECMO and CRRT can be an effective treatment protocol in cases of ineffective conventional medical therapy for hypotension and lactic acidosis due to an overdose of antihypertensive agents and metformin, respectively.

• 약학회지
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• 제58권2호
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• pp.141-149
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• 2014

Background: 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 treatment 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 commonly 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, antihypertensive 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 [$P{\leq}0.05$/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 treatment of hypertension. However, further larger scale or prospective studies are required in order to confirm these results.

• Journal of Preventive Medicine and Public Health
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• 제53권6호
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• pp.476-486
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• 2020

Objectives: The objective of this study was to estimate the risk of lung cancer in relation to angiotensin II receptor blocker (ARB) use among patients with hypertension from the Korean National Health Insurance Service-National Health Screening Cohort. Methods: We conducted a retrospective cohort study of patients with hypertension who started to take antihypertensive medications and had a treatment period of at least 6 months. We calculated the weighted hazard ratios (HRs) and their 95% confidence intervals (CIs) of lung cancer associated with ARB use compared with calcium channel blocker (CCB) use using inverse probability treatment weighting. Results: Among a total of 60 469 subjects with a median follow-up time of 7.8 years, 476 cases of lung cancer were identified. ARB use had a protective effect on lung cancer compared with CCB use (HR, 0.75; 95% CI, 0.59 to 0.96). Consistent findings were found in analyses considering patients who changed or discontinued their medication (HR, 0.50; 95% CI, 0.32 to 0.77), as well as for women (HR, 0.56; 95% CI, 0.34 to 0.93), patients without chronic obstructive pulmonary disease (HR, 0.75; 95% CI, 0.56 to 1.00), never-smokers (HR, 0.64; 95% CI, 0.42 to 0.99), and non-drinkers (HR, 0.69; 95% CI, 0.49 to 0.97). In analyses with different comparison antihypertensive medications, the overall protective effects of ARBs on lung cancer risk remained consistent. Conclusions: The results of the present study suggest that ARBs could decrease the risk of lung cancer. More evidence is needed to establish the causal effect of ARBs on the incidence of lung cancer.

• Journal of Biomedical and Translational Research
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• 제19권4호
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• pp.86-91
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• 2018

Angiotensin receptor blockers, such as telmisartan, are considered effective in the treatment of hypertension and proteinuria due to chronic kidney disease (CKD) in cats. It selectively blocks the $AT_1$ receptor and does not affect the $AT_2$ receptor, thus effectively blocking the activity of the renin angiotensin aldosterone system. This study aims to compare over time the changes in various indicators, including systemic hypertension and proteinuria, before and after the administration of telmisartan in cats with CKD. Decrease in blood pressure (BP) (p<0.001) and urine protein to creatinine (UP/C) ratio (p<0.001) were found to be statistically significant over time after the administration of telmisartan. BP and the UP/C ratio were $160{\pm} 22.2$ and $0.50{\pm}0.647$ before telmisartan administration (Day 0), $150{\pm}21.0$ and $0.27{\pm}0.487$ on the 30th day (Day 30), $150{\pm}17.0$ and $0.25{\pm}0.376$ on the 60th day (Day 60), and $140{\pm}17.8$ and $0.15{\pm}0.233$ on the 90th day (Day 90) after administration, respectively. BP and UP/C were statistically significantly lower in cats with CKD over time at each time point from Day 0 to Day 90 at 30 day intervals. Especially after 90 days of telmisartan administration, the improvement of BP and UP/C were estimated to be about 20 mmHg and 0.35, respectively. In conclusion, the oral administration of telmisartan to cats with CKD is effective in improving BP and proteinuria, which has a positive effect on long-term survival in cats with CKD.

• Childhood Kidney Diseases
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• 제27권2호
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• pp.121-126
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• 2023

The administration of angiotensin type 2 receptor blockers (ARBs) during pregnancy is known to cause ARB fetopathy, including renal insufficiency. We aimed to analyze the outcomes of two patients who survived ARB fetopathy and perform an accompanying literature review. Case 1 was exposed antenatally from a gestational age of 30 weeks to valsartan because of maternal pregnancy-induced hypertension. The patient presented with oliguria immediately after birth, and renal replacement therapy was administered for 24 days. Seven years after birth, renal function was indicative of stage 2 chronic kidney disease (CKD) with impaired urinary concentration. Case 2 had a maternal history of hypertension and transient ischemic attack and was treated with olmesartan until 30 weeks of pregnancy. Renal replacement therapy was performed for 4 days since birth. After 8 years, the patient is with CKD stage 2, with intact tubular function. Recent reports suggest that ARB fetopathy might manifest as renal tubular dysgenesis and nephrogenic diabetes insipidus, in contrast to mild alterations of glomerular filtration. Tubular dysfunction may induce CKD progression and growth retardation. Patients with ARB fetopathy should be monitored until adulthood. The ARB exposure period might be a critical factor in determining the severity and manifestations of fetopathy.

• 한국임상약학회지
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• 제32권2호
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• pp.125-132
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• 2022

Background: Fixed-dose combinations have the advantage of improving patient compliance, but may increase the risk of duplicate prescriptions. As the use of fixed-dose combination antihypertensives increases, it is necessary to investigate the current status of class duplication prescriptions (CDP) in patients taking fixed-dose combination antihypertensives in Korea and to identify factors associated with CDP. Methods: We conducted a retrospective observational study using nationally representative claim data. Hypertensive patients aged 20 years or older taking fixed-dose combination antihypertensives were extracted. Among these patients, patients with CDP were identified. A chi-square test was applied to determine the differences between patients with CDP and non-CDP. The associated factors of CDP were identified through multiple logistic regression. Results: Of the 74,165 patients who were prescribed fixed-dose combination antihypertensives, 426 patients (0.6%) with CDP were identified. The most common antihypertensive class associated with CDP was calcium channel blockers (194 patients, 45.5%), followed by angiotensin II receptor blockers (136 patients, 31.9%). Patients aged 75 years or older (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.02-3.52), chronic kidney disease (OR 4.45, 95% CI 2.15-8.25), chronic heart failure (OR 2.71, 95% CI 1.93-3.72), coronary artery disease (OR 2.22, 95% CI 1.60-3.03) and Medical Aid/Patriots and Veterans Insurance (OR 1.49, 95% CI 1.04-2.07) were significantly associated with increased CDP. Conclusions: The factors associated with CDP were the elderly, comorbidities, and low socioeconomic status. Since CDP can result in negative clinical outcomes, active intervention by the pharmacist is warranted.

• Journal of Medicine and Life Science
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• 제19권3호
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• pp.79-89
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• 2022

Whereas systolic blood pressure (SBP) continuously rises with age, diastolic blood pressure (DBP) gradually decreases after the age of 55 years. Therefore, hypertension in the elderly shows the pattern of isolated systolic hypertension. There is evidence on the benefits of controlling blood pressure (BP) in elderly patients with hypertension. The BP lowering effect has also been demonstrated in patients over 80 years of age with hypertension. The BP threshold for the initiation of antihypertensive drug treatment for older adults with hypertension is gradually decreasing. The antihypertensive treatment is recommended if, despite therapeutic lifestyle modifications, SBP ≥140 mmHg or DBP ≥90 mmHg in those aged 65-79 years old, and SBP ≥140-160 mmHg or DBP ≥90 mmHg in those aged ≥80 years old. Although there is no consensus on the target BP for older adults with hypertension, a target SBP of <130-140 mmHg and DBP of <80-90 mmHg are recommended. In older adults over 80 years of age with hypertension, the target SBP is <140-150 mmHg. When the dose of antihypertensive drugs is increased to reach the target SBP, DBP may decrease to less than 70 mmHg, but it should not be <60 mmHg. Thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers can be selected as the first-line drug for older adults with hypertension. Beta-blockers may be selected in case of compelling indications.

• Childhood Kidney Diseases
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• 제28권2호
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• pp.51-58
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• 2024

Patients with chronic kidney disease (CKD) bear a significant financial burden and face numerous complications and higher mortality rates. The progression of CKD is associated with glomerular injury caused by glomerular hyperfiltration and oxidative stress. Factors such as uncontrolled hypertension, elevated urine protein levels, anemia, and underlying glomerular disease, contribute to CKD progression. In addition to conservative treatment, several medications are available to combat the progression of CKD to end-stage kidney disease. Renin-angiotensin-aldosterone system blockers could slow the progression of CKD by reducing glomerular hyperfiltration, lowering blood pressure, and decreasing inflammation. Mineralocorticoid receptor antagonists inhibit the mineralocorticoid receptor signaling pathway, thereby attenuating inflammation and fibrosis. Sodium-glucose cotransporter 2 inhibitors exhibit protective effects on the kidneys and against cardiovascular events. Tolvaptan, a selective vasopressin V2-receptor antagonist, decelerates the rate of increase in total kidney volume and deterioration of kidney function in patients with rapidly progressive autosomal dominant polycystic kidney disease. The protective effects of AST-120 remain controversial. Due to a lack of evidence regarding the efficacy and safety of these medications in children, it is imperative to weigh the benefits and adverse effects carefully. Further research is essential to establish the efficacy and safety profiles in pediatric populations.

• 한국임상약학회지
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• 제21권4호
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• 대한약리학회지
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• 제30권3호
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• pp.337-342
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• 1994

선천성고혈압흰쥐 (SHR)에서 angiotensin converting enzyme inhibitor (ACEI)를 처치하면 내피세포 의존적 이완이 증진된다고 알려져 있다. 본 실험은 angiotensin II가 nitric oxide (NO)와 관련되어 일어나는 적출 대동맥의 이완력에 변화를 주는지 관찰하고자 angiotensin II 작용 억제를 위해 angiotensin II 수용체 차단제인 losartan과 ACEI인 enalapril을 사용하였으며 혈관에서의 NO는 혈관내피세포에서 생성되는 constitutive NO와 주로 혈관 평활근에서 LPS에 생성되는 inducible NO가 있으므로 이들 양자에 대한 angiotensin II의 작용을 검토하였다. 2주간 losartan (30 mg/kg/day)과 enalapril (10 mg/kg/day)을 처치한 경우 acetylcholine $(10^{-9}\;to\;10^{-5}\;M)$과 histamine $(10^{-8}\;to\;10^{-4}\;M)$에 의한 이완 반응이 증가되었으나 90분간 적출 대동맥에 losartan $(10^{-4}\;M)$ 을 노출시킨 경우는 이완 반응에 변화가 없었다. Phenylephrine $(10^{-7}\;M)$ 을 2시간 간격으로 반복 투여하여 수축시킨 경우 LPS $(100\;{\mu}g/ml)$처치에 의해 시간이 지남에 따라 수축력이 감소되었고 대조군에서는 수축력이 감소되지 않았다. LPS 처치에 따른 phenylephrine에 의한 수축력의 감소는 enalapril이나 losartan을 2주간 처치한 경우에도 영향을 받지 않았다. 이상의 결과로 미루어 아마도 losartan의 내피세포에 대한 작용은 constitutive NO 생성을 증가시키나 inducible NO 생성에는 영향을 미치지 않을 것으로 여겨진다.