• YAKHAK HOEJI
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• v.25 no.2
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• pp.57-64
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• 1981

The antihypertensive effect of $\alpha-Methyldopa$ administered concurrently with timolol or labetalol were studied with spontaneously hypertensive rats (SHR). Every drugs were administered orally once a day after prechecking the systolic blood pressure and heart rate of SHR. The blood pressure and heart rate of SHR were significantly decreased in groups of combination while those of non-combination groups were fallen slightly. Compared with control group, the significant changes of blood pressure was obseved in group of $\alpha-methyldopa$ with timolol(100mg+2mg/kg)and $\alpha-methyldopa$ with labetalol (100mg+12.5mg/kg). The group of $\alpha-methyldopa$ with timolo 1 (100mg + 1.0mg/kg) reduced blood Pressure in similar degree as manifested in group of $\alpha-methyldopa$ with labetalol (100mg + 50mg/kg). In the group that $\alpha-methyldopa$ was administered concurrently with timolol, the maximum antihypertensive effect and heart rate decreasing effect were appeared after 3hr and 1hr of administration respectively and those effects in group of $\alpha-methyldopa$ with labetalol were appeared after 6hr of administration. The acute oral toxicity test was performed using albino mice with $\alpha-methyldopa$ alone, $\alpha-methyldopa$ with timolol (100:1) and $\alpha-methyldopa$ with labetatol (4:1), and was found that the $LD_{50}$ of $\alpha-methyldopa$ alone was 1104 mg/kg, $\alpha-methyldopa$ with timolol (100:1) was 1115 mg/kg and $\alpha-methyldopa$ with labetalol (4:1) was 354mg/kg.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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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.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

• Journal of the Korean Chemical Society
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• v.55 no.2
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• pp.268-278
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• 2011

Corrosion of aluminum in 0.1 M HCl solution in the absence and presence of ${\beta}$-blocker inhibitors (atenolol, propranolol, timolol and nadolol) was investigated using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The inhibition efficiency increased with inhibitor concentration and decreased with rise of temperature. Potentiodynamic polarization curves revealed that they acted as cathodic inhibitors. Some thermodynamic parameters were calculated and discussed. All inhibitors were adsorbed on Al surface obeying Frumkin isotherm. All EIS tests exhibited one capacitive loop which indicates that the corrosion reaction is controlled by charge transfer process. The inhibition efficiencies of all test methods were in good agreement.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.219.3-219.3
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• 2003

We describe here solid-extraction and derivatisation methods of ${\beta}$-adrenoceptor blocking drugs used for the treatment of various cardiovascular disorders such as hypertension, angina pectoris and cardiac arrhythmia: propranolol, metoprolol, sotalol, timolol, oxprenolol, alpranolol, atenolol, pindolol. Solid-extraction and derivatisation methods are described involving the use of Bond Elut Certify cartridges, MSTFA and MBTFA. Gas chromatographic-mass spectrometry analysis(GC/MS) was carried out select-ion monitroing mode. (omitted)

• Journal of Veterinary Science
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• v.24 no.1
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• pp.6.1-6.6
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• 2023

Two Shih-Tzu dogs with atopic dermatitis presented with delayed periocular dermatitis (PD) following the instillation of dorzolamide and dorzolamide/timolol combination eyedrops; the development of dermatologic signs took 94 and 104 d in cases 1 and 2, respectively. Hypersensitivity to anti-glaucoma eyedrops was highly suspected, and treatment was discontinued. Delayed PD was significantly relieved in cases 1 and 2, at days 155 and 64 after discontinuation, respectively. In this study, the clinical characteristics and progression of delayed PD were described to inform clinicians who may encounter this rare side effect.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.2
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• pp.681-693
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• 2019

Multi-use ophthalmic solutions are used many times after opening; therefore, there is a high possibility of decreased quality during use. This study was conducted to determine the recommended use period of multi-use ophthalmic solutions based on evaluation of the stability by comparing stability evaluation regulations of the USA, EU and Korea We selected four types of multi-use ophthalmic solutions (Olopatadine (Olo), Fluorometholone (Flu), Dorzolamide (Dor), Timolol (Timol)) that are frequently marketed in Korea and evaluated their stability during storage according to the actual usage method after opening. The Olo had a decrease in assay and preservative content at 2 months after opening, while Flu showed a significant difference from day 28 after opening. For Dor, significant differences were observed from day 14 after opening in the assay and impurity test item and Timol showed a significant difference from day 28 after opening. Based on the results of the stability test Olo and Flu should only be used within 28 days of opening, while Dor and Timol should be used within 14 days of opening. Therefore, we suggest that regulations system related use periods of multi-use ophthalmic solutions designed as aseptic preparations should be improved based on the results of stability tests after opening.

• Korean Journal of Clinical Pharmacy
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• v.31 no.3
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• pp.205-215
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• 2021

Background: The treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT) for intraocular pressure (IOP) reduction is recommended to proceed with the use of the compound. Therefore, this study aimed to evaluate the efficacy and safety of brinzolamide combination therapy on POAG and OHT following the subgroup analysis among types of brinzolamide combined medications. Methods: By June 2019, PubMed, EMBASE and Cochrane Library were searched to find a study that met our inclusion criteria. Based on randomized control trials (RCTs), we collected studies that tested the brinzolamide combination therapy in POAG and OHT patients, and analyzed the literature identified by the results of the study on IOP reduction and adverse reactions. Results: A total of 13 literature was collected to conduct an analysis including 2,197 patients. The intervention included brinzolamide combination therapies, combined with timolol, brimonidine, PGA or combined with both brimonidine and PGA. The analysis showed significant decreasing tendency for values at morning and end treatment per day in the use of brinzolamide combination therapy in the absolute IOP change (mean difference (MD) -1.41; 95% CI -1.92, -0.90; p<0.001 vs. MD -1.46; 95% CI -2.03, -0.89; p<0.00001, respectively). We could see higher adverse reactions in the brinzolamide combination group using intervention (odds ratio 1.43; 95% CI 1.20, 1.71; p<0.0001). Conclusion: Regarding IOP reduction in POAG and OHT patients, brinzolamide combination therapy is more effective but less safe than control treatment, which diverse among types of combined medications. Thus, more individualized therapy should be applied in real-world practice.

• Clinical and Experimental Pediatrics
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• v.64 no.11
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• pp.559-572
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• 2021

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%-10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2-3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1-2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.