• Tuberculosis and Respiratory Diseases
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• 제43권3호
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• pp.308-322
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• 1996

연구배경 : 히스타민은 폐혈관주위의 비만 세포내에 풍부하게 분포하니 아직까지 급성 폐손상의 병리기전에 있어 히스타민의 역할에 대해서는 규명되어 있지 않았다. 히스타민은 IL-1 이나 IL-8과 같은 cytokine 사이에 상호작용이 있고 혈관내피 표면상에 P-selectin의 표현을 증가시키는 것으로 알려져 있다. 이에 저자들은 건강한 백서의 기도내로 침윤이 증가되며 히스타민과 TNF를 병용 투여서는 TNF 단독 투여사보다 폐장내 호중구의 침윤이 증폭되고 폐손상의 정도가 증가 될 것으로 가정하였다. 방법 : 몸무게 270-370gm인 Sprague-Dawley 쥐를 사용하여 정상군은 생리식염수 0.5mL을, 치료군은 체증 1Kg 당 $1.1{\mu}g$, $11{\mu}g$ 및 $55{\mu}g$의 히스타민을 단독 혹은 TNF 500ng과 함께 병용하여 기도로 투여하거나 히스타민 $55{\mu}g$과 IL-1 50ng을 병용투여 한 뒤 5시간 뒤 에 폐조직 내 myeloperoxidase(MPO) 활성도와 폐포액내 호중구 수 및 쥐의 IL-8으로 고려되는 cytokine-induced neutrophil chemoattractant(CINC)의 활성도 그리고 폐혈관내 알부민의 폐조직내로의 누출을 측정하였다. 또한 TNF와 히스타민을 병용투여한 뒤 TNF와 히스타민 병용치료군에 항히스타민제를 경정맥내로 주입한 뒤 동일한 방법으로 각 지표들을 측정하여, 관찰된 상승효과가 차단되는지를 보았다. 곁과 1) TNF치료군은 정상군에 비하여 폐장내 MPO 활성도, 기관폐포액내 홍중구수 및 폐혈관의 누출이 더 높게 나타났으며(각 p<0.001), 히스타면 투여군은 11 및 $55{\mu}g/kg$ 투여군에서 정상군에 비해 MPO 활성도만이 높게 나타났다(p<0.05) 2) 폐장내 MPO 활성도는 기도내로 TNF와 병용투여한 히스타민 $1.1{\mu}g$군, $11{\mu}g$군 및 $55{\mu}g$ 군 모두에서 정상군에 비해 증가되어 나타났으며(각 p<0.001) 히스타민 $11{\mu}g/kg$ 병합투여군에서는 TNF 단독치료군에 비해서도 높게 나타났다(p=0.0251). 기관폐포액내 호중구의 수는 히스타민 1.1, 11 및 $55{\mu}g/kg$군 모두에서 정상군(p<0.05)에 비해 증가되어 나타났으며 $1.1{\mu}g/kg$군은 TNF 단독치료군에 비해서도 높았다(p=0.0367). 급성 폐혈관 히스타민 $1.1{\mu}g$군, $11{\mu}g$군 $55{\mu}g$군에서 정상군에 비해 증가되었으나(p<0.001), TNF 치료군과는 차이가 없었다. 3) TNF와 히 스타민 1.1, 11 및 $55{\mu}g/kg$이 병용투여된 군 모두에서 정상군에 비해 폐포 세척액내 CINC 활성도가 유의하게 증가되었다(각각 p-값<0.01 및< 0.05) 4) $H_1$ 수용체차단제인 mepyramine과 $H_2$ 수용체차단제인 ranitidine 세척액내 증폭되었던 호중구 수 및 CINC의 활성도를 감소시켰다(각각 p-값>0.05) 5) IL-1과 병용 투여한 히스타민은 정상군에 비해 MPO 활성도 및 급성 폐혈관 누출이 증가되었으나(p<0.05), IL-1 치료군과는 차이가 없었다. 결론 : 본연구의 결과로서 백서의 기도내로 국소적으로 히스타민을 투여시 5시간 이내에 폐조직내 호중구의 침윤이 증가되고 TNF로 유도된 폐조직내 MPO 활성도 및 기관폐포액 내 호중구 수의 증가가 증폭되나 폐혈관내 알부민의 폐장내 누출의 증폭작용이 없고 IL-1으로 유도된 폐손상에도 급성 폐손상의 증폭작용이 관찰되지 않으므로 TNF나 IL-1으로 유도되는 급성 폐손상에 히스타민 병용 투여에 의한 폐손상의 증폭작용은 없을 것으로 사료되었다.

• 한국임상약학회지
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• 제7권1호
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• pp.22-32
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• 1997

The gastrointestinal disorders (GI disorders) is one of the most common diseases in Korea. The community pharmacists are often faced with the complaints of symptoms due to the GI disorders. However the drugs used to treat the GI disorders are frequently abused by the patients themselves because these drugs are easily available and have high placebo effects. Therefore, we have reviewed the digestive diseases statistics of 1996 to find out the frequencies of the GI disorders in the outpatients of Samsung Medical Center. Using these statistic data, we figured out the frequently diagnosed GI disorders and analysed commonly used prescriptions from February 1st to 28th of 1997. In addition, we also evaluated the commonly used drugs in these prescriptions. About twenty thousands of patients visited the hopital because of their GI symptoms in 1996. It was found that dyspepsia, viral hepatitis, and gastric and duodenal ulcer disease are frequently diagnosed in these patients. In a point of view on other GI disorders, gastritis and duodenitis, irritable bowel syndrome, gastroesophageal reflux disease, constipation and diarrhea were commonly detected. And a number of drugs were prescribed to treat the GI disorders, which included the prokinetics, Histamine-2 receptor antagonists, proton pump inhibitor, antacids, tranquillizers, antidepressants, antispasmodics, laxatives and so on. Interestingly, there were many prescriptions composing of the antibiotic regimens to eradicate H. pylori which has been proven to cause peptic ulcers.

• 대한기관식도과학회지
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• 제10권2호
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• pp.22-27
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• 2004

Background : LPRD(Laryngopharyngeal reflux disease) gives rise to inflammatory change in the pharyngolaryngeal tissue with various otolaryngologic symptoms. Ranitidine, histamine H2receptor antagonists, are currently used as therapeutic medications. However, the efficacy of Ranitidine on LPRD has not been proven yet. Objectives : We intended to analyze the efficacy of the Ranitidine on LPRD. Materials :md Methods : In 20 multicenter, 607 patients with LPR(laryngopharyngeal reflux) symptom were observed to evaluate their symptoms and laryngoscopic findings after 4 weeks, 8 weeks, and 12 weeks of treatment of Ranitidine. Results : The symptom of LPR including globus sensation, sore throat hoarseness, regurgitatioin are improved after 4 weeks $86.2\%,\;8 weeks\;91.5\%,\;12 weeks\;92.9\%$ of Ranitidine treatment and improved after 4 weeks $91.5\%,\;8 weeks\;94.5\%,\;12 weeks\; 97.2\%$ of Ranitidine combined with prokinetics. The rates of sore throat, chronic cough, globus sensation improvement at 8 weeks after treatment are $26.7\%,\;16.7\%,\;16\%$. Conclusion : In patient with LPR, Ranitidine treatment reduces LPR symptoms very effectively.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.252-252
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• 1996

We Investigated the peripheral excitatory effect of capsaicin and KR-25018, a newly synthesized capsaicin derivative which was demonstrated to have a potent analgesic activity. KR-25018 and capsaicin were found to be both potent efficacious contractors of isolated guinea pig bronchial smooth muscle. KR-25018 was equipotent with capsaicin and [Sar$\^$9/,Met(O$_2$)$\^$11/]-substance P, 10-fold more potent than histamine and 10-fold less potent than (${\beta}$ -Ala$\^$8/)-neurokinin A(4-10), and their -log(M)EC$\_$50/ values were 6.94${\pm}$0.08, 6.86${\pm}$0.05, 6.96${\pm}$0.07, 5.64${\pm}$0.04, 7.96${\pm}$0.02, respectively. Contractile responses to KR-25018 and capsaicin were potentiated by phosphoramidon (1 ${\mu}$M), an inhibitor of neuropeptide-inactivating endopeptidase, but completely abolished in a calcium-free medium. These responses to KR-25018 and capsaicin were unaffected by the NK-1 antagonist CP96345 (1${\mu}$M), partially inhibited by the NK-2 antagonist SR48968 (1 ${\mu}$M) but almost completely abolished by a combination of the antagonists. A vanilloid receptor antagonist capsazepine competitively antagonized the responses to both KR-25018 and capsaicin (pA$_2$: aganst KR-25018, 5.98${\pm}$0.47; against capsaicin, 5.80${\pm}$0.31), and a capsaicin-sensitive cation channel antagonist ruthenium red caused significant reduction in the maximum responses to KR-25018 and capsaicin (pD'$_2$: against KR-25018, 4.61${\pm}$0.33; against capsaicin 4.96${\pm}$0.21). In conclusion, the present results suggest that KR-25018 and cpasaicin act on the same vanilloid receptor inducing the influx of calcium through ruthenium red-sensitive cation channel and produce contractile responses via the release of tachykinins that act on both NK-1 and NK-2 receptor subtypes.

• 한국임상약학회지
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• 제16권1호
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• pp.34-39
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 120 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration(KFDA). The test product was Hanmi Fexofenadine Hydrochloride Tablet $120mg^{(R)}$ made by Hanmi Pharm. Co. and the reference product was Allegra Tablet $120mg^{(R)}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2{\times}2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t\;and\;C_{max}$ were log $0.844{\sim}log$ 1.149 and log $0.833{\sim}log$ 1.109, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet 120 mg is bioequivalent to Allegra Tablet 120 mg.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.53-58
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 180 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Hanmi Fexofenadine Hydrochloride $Tablet^{\circledR}$ made by Hanmi Pharm. Co. and the reference product was Allegra $Tablet^{\circledR}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2\;{\time}\;2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were $log\;0.822{\sim}log \;1.142$ and $log\;0.848{\sim}log\;1.172$, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet is bioequivalent to Allegra Tablet.

• 사상체질의학회지
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• 제26권2호
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• pp.205-212
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• 2014

Objectives Adverse reactions can becaused by contrast media used in computed tomography. The aim of this study was to report the improvement of allergic response caused by contrast media after treatment with Modified Hyeongbangpaedok-san, histamine antagonists and steroids. Methods We retrospectively reviewed the medical records. The patient's subjective symptoms such as rash and pruritus were evaluated by the range of rash and numeric rating scale(NPS). Results All symptoms showed nearly complete remission with continued Korean traditional medical treatment. Conclusions A female patient had been injected with contrast media for Computed tomography(CT) evaluation of lung cancer. Rash and pruritus appeared 1 day after injection. We prescribed Modified Hyeongbangpaedok-san. Patients were treated with both Korean medicine and Western medicine. Consequently, the symtoms were improved significantly after combination treatment of Korean medicine and Western medicine.

• 대한약리학회지
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• 제24권2호
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• pp.203-216
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• 1988

돼지, 가표 및 가토의 뇌동맥에서 기저동맥 (basilar artery, BA)과 circle of willis동맥 (WC)의 동맥환을 만들어 혈관수축제와 calcium 길항제의 효과 그리고 내피세포의 역할은 검토하였다. 돼지 BA와 WC에 서 norepinephrine (NE), phenylephrine (PE)및 epinephrine (EP)은 propranolol $10^{-6}M$ 전처리하에서 그리고 KCI, histamine, 5-hydroxytryptamine (5-HT) 및 angiotensin은 모두 용량의존성 수축반응을 일으켰다. 그 최대수축력은 angiotensin에서 가장 적었고, 5-HT에서 가장 강력하였다. KCI 35 mM수축반응은 calcium 길항제로 용량의존성으로 억제되었고, 그 효력은 nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glycerl trinitrate의 순서였다. 5-HT $10^{-5}M$의 수축반응은 nifedipine으로는 용량의존성으로 억제 되었으나 diltiazem과 ISDN으로는 경미한 억제만을 일으켰다. 내피세포동맥환에서 KCI 35 mM의 수축반응은 acetylcholine (ACh)으로 거의 영향받지 않았으나 $PGF_{2{\alpha}}\;10^{-5}M$의 수축반응은 ACh과 adenosine으로 용량의존성으로 억제되었고, 이 내피세포 의존성억제는 nifedipine $10^{-6}M$로는 영향받지 않으나 methylene blue $50\;{\mu}M$로는 현저히 억제되었다. 네피제거동맥환에의 $PGF_{2{\alpha}}$의 수축반응은 ACh의 영향이 없거나 더욱 수축되었다. 내피세포를 제거하지 않은 가토흉부대동맥편을 bath에 함께 넣어주면 ACh의 용량의존성 이완반응이 나타났고 이 이완반응도methylene blue로 억제되었다. 가묘 BA와 WC에서 5-HT와 NE는 용량의존성 수축반응을 일으켰고 ACh도 내피세포 존재유무와 관계없이 강력한 용량의존성 수축반응을 일으켰으며 그 최대수축력은 ACh에서 가장 강력하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh에 의하여 이완반응없이 더욱 수측되었다. 가토 BA에서 5-HT와 NE는 응량의존성 수축반응을 일으졌고5-HT의 수축반응이 더욱 현저하였다. 내피세포동맥환에서 5-HT $10^{-5}M$의 수축반응은 ACh $10^{-5}M$로 현저하게 이완되있고 이 내피세포의존성 이완반응은 atropine $10^{-7}M$로는 억제되었으나 diltiazem $10^{-6}M$로는 거의 억제되지 않았다. 이상의 실험성적은 돼지와 가토의 뇌동맥에서 ACh은 내피세포-의존성 이완반응을 일으키며그 이완반응은 muscarinic receptor를 통해 나타났고, 가묘뇌동맥에서 ACh은 혈관수축제의 역할을 갖고 있음을 시사하고 있다.