• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.55-62
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• 1998

${\alpha},\;{\beta}-Adrenergics$, and calcium channels were known to be related to inducing cardiac hypertrophy. Recently, it was reported that the cardiac renin-angiotensin system (RAS) was an important factor in ventricular hypertrophy. The present study was aimed to investigate the effects of ${\alpha},\;{\beta}-adrenergic$, and calcium channel blockers that might be involved in the regulation of cardiac RAS. The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of renin gene in the perfused rat heart. Changes in angiotensin converting enzyme (ACE) activity and cyclic AMP (cAMP) content which were thought to play a role in inducing cardiac hypertrophy were measured in the perfused rat heart. The expression of renin gene was not only increased by isoproterenol with metoprolol-pretreatment but also increased by vasopressin treatment in the presence of calcium channel blocker, nifedipine or verapamil. Either prazosin alone or norepinephrine with prazosin-pretreatment significantly increased the ACE activity. However, isoproterenol with metoprolol-pretreatment significantly decreased the ACE activity. On the other hand, the ACE activity was not changed by vasopressin, nifedipine, or verapamil treatments. The content of cAMP was significantly increased by either isoproterenol or vasopressin treatment. According to these results, renin gene expression was associated with ${\beta}2$ - adrenoceptor and calcium channel. ACE activity was associated with ${\alpha}-\;and{\beta}2$ - adrenoceptor. In conclusion, ${\beta}2$ - adrenoceptor was important in cardiac renin gene expression and ACE activity and ${\alpha},\;{\beta}$ -adrenergic, and calcium channel blockers might be involved in the regulation of cardiac RAS in a complicated way.

• Journal of Pharmaceutical Investigation
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• 제24권3호spc1호
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• pp.59-66
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• 1994

The objective of this study was to determine the influence of drug lipophilicity on the extent of ocular and systemic absorption following topical solution instillation in the pigmented rabbit. ${\beta}-Blockers$ of various lipophilicity were chosen as model drugs, $25\;{\mu}l$ of a 15 mM drug solution in isotonic pH 7.4 buffer was instilled, and ocular tissue and plasma drug concentrations were monitored. Ocular absorption was apparently increased in all eye tissues, but non-corneal absorption ratio was decreased by increasing of drug lipophilicity. Systemic bioavailability was ranged from 61% for atenolol to 100% for timolol, and at least 50% of the systemically absorbed drug reached the blood stream from the nasal mucosa. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol, but did not do so for atenolol and betaxolol. Taken together, the ocular absorption of topically applied ophthalmic drugs would be modest for lipophilic drugs. By contrast, the systemic bioavailability would be modest for drugs at the extremes of lipophilicity, and the nasal contribution to systemically absorbed drug diminished with increasing of drug lipophilicity.

• KSBB Journal
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• 제13권1호
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• pp.71-76
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• 1998

$Na^+$ 전극도 개구리 방광막으로 만들어진 조직센서를 이용하여 복어독 (TTX), 조개독 (STX), 마비성조개독 (PSP) 등의 $Na^{+}$ 챈널 차단물질을 측정하였다 본 연구는 연속적으로 $Na^{+}$ 챈널 차단물질을 측정할 수 있는 조직 센서를 이용하여 한국산 한방약의 재료와 건조 및 생김 (Porphyra yezoensis)의 $Na^+$ 챈널 차단물질의 존재여부를 측정하였다. 본 센서는 한방약 재료 및 해조류 (김 등)와 같이 현재 일반적으로 사용되고 있는 마우스법으로 측정이 불가능한 fg 단위의 매우 적은 양의 $Na^{+}$ 챈널 차단물질까지 측정이 가능하였다. 본 바이오센서는 $Na^{+}$ 챈널 차단물질의 모니터링 및 해양환경감시에 응용 가능하리라 기대된다.

• 대한약리학회지
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• 제32권2호
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• pp.211-219
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• 1996

The inhibitory effect of cyclosporin A (CsA) on nitric oxide production is not related to the immunosuppressive action of the drug, but to the renal toxicity and arterial hyper-tension. In this study the experimental interventions to reverse the inhibition of nitric oxide production by cyclosporin A in rat aortic smooth muscle cells were examined. CsA inhibited the accumulation of nitrite, the stable end product of nitric oxide, in culture media in a concentration $(0.1{\sim}100{\mu}g/ml)-dependent$ manner. The inhibitory effect of CsA on nitrite accumulation were not antagonized by arginine (10 mM), a substrate of nitric oxide synthase, nor by calcium ionophore A23187 $(7{\mu}M)$. Forskolin, an activator of adenylate cyclase, which enhanced iNOS induction at transcriptional level, completely reversed the inhibitory action of CsA on nitrite accumulation. However, PMA (2 nM) and PDB (50 nM), PKC activators, increased the inhibitory action of CsA on nitrite accumulalion. From these results, it is suggested that cyclic AMP-elevating agents may be candidates of therapeutic agents in prevention and treatment of renal toxicity and arterial hypertension induced by CsA. Among conventional antihypertensive drugs, calcium channel blockers and ${\alpha}-blockers$ are preferred to ${\beta}-blockers$.

• 분석과학
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• 제34권1호
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• pp.9-16
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• 2021

In the group of commonly prescribed β-blocker drugs, one of the enantiomers is generally relatively more active than the others. This study aims to develop a technique for the chiral analysis of select β-blockers based on proton nuclear magnetic resonance (1H-NMR) spectrometry. (S)-2-Tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid ((S)-TBMB) was synthesized and utilized as a chiral derivatizing agent. Pure β-blocker enantiomers were isolated from racemates by semi-preparative liquid chromatography prior to derivatization. The reaction time and concentration of (S)-TBMB were controlled to improve the derivatization procedure. No racemization was found during the analysis. High-performance liquid chromatography (HPLC) analysis was also performed for comparative purposes. High agreement between the NMR and HPLC methods was achieved in the determination of (R)-metoprolol in a standard solution of the (S) isomer.

• 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.

• Journal of Preventive Medicine and Public Health
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• 제42권3호
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• pp.165-170
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• 2009

Objectives : We evaluated the risk of fracture associated with hypotension-related adverse drug reaction caused by taking alpha blockers to treat benign prostatic hyperplasia (BPH). Methods : We used the Health Insurance Review and Assessment Service database from January 1st 2005 to June 30th 2006 for this study. The male patients with BPH and who had a prescription for alpha blockers following any fractures were defined as the cases. We set the 20 day long hazard period prior to the index date and the four control periods whose lengths were same with hazard period. After 1:4 matching of the hazard and control periods, conditional logistic regression was used to calculate the odds ratios for the risk of fractures as related to the alpha blocker exposure. Results : Doxazosin and tamsulosin showed the increased risk of fractures, whereas terazosin did not. After stratification using the defined daily doses, a protective effect was shown for the patients who took terazosin at the doses lower than 0.4 DDD and the hazardous effect at the doses higher than or equal to 0.4 DDD. There was no significant difference for the risk of patients taking tamsulosin at the doses higher than 1.0 DDD but there was a statistically significant increase in the risk at the doses higher than or equal to 1.0 DDD. Conclusions : Alpha blockers for BPH may increase the risk of fracture in elderly patients who have comorbidities and take the concomitant medications. Alpha blockers need to be prescribed with caution, although some have high prostate specificity.

• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 2002년도 제19차 학술대회
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• pp.269-274
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• 2002

• International Journal of Heart Failure
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• 제6권3호
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• pp.127-128
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• 2024

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.217-217
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• 1994

Calcium entry blockers, capable of inhibiting transmembrane influx of extracellular calcium through specific calcium channels, are useful drugs in the treatment of angina pectoris, hypertension, cardiac arrythmia, and various cardiovascular disorders. Compounds having isoquinoline structures have recently been reported to possess calcium antagonistic action. Therefore, in the present study, we have attempted to synthesize some isoquinoline and related compound.; in order to search for potentially effective chemicals acting on cardiovascular system, and evaluated their pharmacological properties focusing on calcium antagonistic actions. Almost all of the compounds so far synthesized, had inhibitory action against phenylephrine or high potassium-induced contraction in vascular smooth muscle with different degrees of potencies depending on their structures, However, some of tetrahydroisoquinoline analogs showed directly inhibit calcium current in isolated rabbit cardiac myocytes examined by patch clamp techniques. The pharmacological properties of these compounds need more intensive investigation as to whether these chemicals may have developed as a new cardiovascular active drugs. Therefore, we are now under investigation of the mechanism of action of these compounds.