Influence of Co-administered Drugs on Shakuyaku-kanzo-To Induced Hypokalemia

Tsukamoto, Akiko; Homma, Masato; Kambayashi, Yasuyuki; Kizu, Junko; Kohda, Yukinao

doi:10.5649/jjphcs.33.687

Jpn. J. Pharm. Health Care Sci.

2007

DOI: 10.5649/jjphcs.33.687

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Influence of Co-administered Drugs on Shakuyaku-kanzo-To Induced Hypokalemia

Akiko Tsukamoto¹,

Masato Homma²,

Yasuyuki Kambayashi³

et al.

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Cited by 4 publications

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“…However, these medicines are usually prescribed concomitantly with Western medicines, which poses a risk of interaction. [13][14][15][16][17] Kampo medicines contain many kinds of glycosides as the main and/or active constituents. Most glycosides tend to be metabolized by enzyme-producing intestinal microbiota before being absorbed into the body.…”

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confidence: 99%

Rhein 8-<i>O</i>-β-D-Glucopyranoside Elicited the Purgative Action of Daiokanzoto (Da-Huang-Gan-Cao-Tang), Despite Dysbiosis by Ampicillin

Takayama

Tabuchi

Fukunaga

et al. 2016

Biological & Pharmaceutical Bulletin

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Sennoside A (SA), the main purgative constituent of Daiokanzoto (da-huang-gan-cao-tang; DKT), is generally regarded as a prodrug that is transformed into an active metabolite by β-glucosidase derived from Bifidobacterium spp. It has been suggested that antibiotics would promote dysbiosis, and thereby inhibit the purgative activity of DKT. In this study, ampicillin was administered to mice for 8 d, and the changes in the SA metabolism of SA alone and of DKT were investigated. The results showed that the SA metabolism of SA singly continued to be inhibited by ampicillin, but that of DKT was activated from day 3 under the same conditions. In order to investigate the mechanism of SA metabolism activated by DKT in the mice administered ampicillin, changes in the SA metabolism were observed in the presence of rhein 8-O-β-D-glucopyranoside (RG) in rhubarb and liquiritin in glycyrrhiza, both of which accelerated the SA metabolism. In fact, RG achieved an activation of SA metabolism similar to that by DKT. The purgative action of DKT, which was continued treatment of the ampicillin, was significantly greater than that by SA alone, and it was shown that RG was involved in this effect. We also analyzed changes in the intestinal microbiota before and after administration of ampicillin. No Bifidobacteria were detected throughout the treatment, but the population of Bacteroides was significantly increased after 3 d under the same conditions. Taken together, these results strongly suggested that the RG in DKT changed the function of Bacteroides and thereby allowed DKT to metabolize SA. Key words Daiokanzoto; sennoside A; rhein 8-O-β-D-glucopyranoside; Bacteroides; Bifidobacterium; microbiotaKampo is a system of traditional Japanese medicine developed from traditional medicine practices in ancient China. Kampo medicines incorporate multiple herbal medicines, they exhibit various pharmacological actions and are prescribed for a range of diseases. Daiokanzoto (da-huang-gan-cao-tang; DKT) is a Kampo medicine that consists of rhubarb and glycyrrhiza; it was demonstrated to be useful for constipation in a clinical double-blind study.1,2) The purgative action of DKT is generally ascribed to the transformation of sennoside A (SA), the main laxative constituent in rhubarb, to an active metabolite, rheinanthrone, by the β-glucosidase derived from Bifidobacterium spp. [3][4][5] (Fig. 1). The purgative action of the SA conversion to rheinanthrone has been explained in terms of Na + /K + transport, water and mucus secretion in the colon. 6,7)This process, which also involves aquaporin-3, was described in detail in recent report. 8) We have also demonstrated that the metabolic activity of SA in intestinal microbiota was significantly accelerated when rhein 8-O-β-D-glucopyranoside (RG) in rhubarb or liquiritin (LQ) in glycyrrhiza coexisted with SA.9-11) Moreover, the purgative action of SA was significantly intensified when RG and LQ were co-administered orally to mice. 10,12) These results show that the influence of these constituents on th...

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confidence: 99%

Rhein 8-<i>O</i>-β-D-Glucopyranoside Elicited the Purgative Action of Daiokanzoto (Da-Huang-Gan-Cao-Tang), Despite Dysbiosis by Ampicillin

Takayama

Tabuchi

Fukunaga

et al. 2016

Biological & Pharmaceutical Bulletin

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Education Program of Kampo-medicine for Undergraduates in Preparation for Clinical Setting

Homma

2016

YAKUGAKU ZASSHI

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Kampo-medicine has become popular in Japanese medical practice combined with western medicine. For example, Daikenchu-To for intestinal obstruction after surgical operation, Shakuyakukanzo-To and Goshajinki-Gan for anticancer agents-induced neuropathy, and Yokkan-San for behavioral psychological symptoms of dementia are alternatively used in addition to conventional treatments in Japan. However, combined use of Kampo-medicine and western medicine may cause unexpected adverse events including undesirable drug-drug interactions because Kampo-medicine was not originally developed to be used with western medicine. Although adverse eŠects of Kampo-medicine are rare compared with those of western medicine, severe events such as liver dysfunction and interstitial pneumonia have been reported in increasing trends. Medical staŠ including pharmacists, therefore, should be aware of the onset of adverse events before the patients' symptoms become severe. Several adverse eŠects are caused by chemical constituents such as glycyrrhizin in licorice for pseudoaldosteronism and geniposide in Gardeniae fructus for mesenteric phlebosclerosis. To understand the adverse eŠects of Kampo-medicine, pharmacists should learn trends in current medication as well as pharmacology and toxicology of the chemical constituents in pharmacognosy. These issues should also be addressed in educational materials for students of clinical pharmacy and pharmacy practice.

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Clinical Characteristics of Side Effects Induced by Administration of Glycyrrhizae Radix and Scutellaria Radix under the Therapy Based on Kampo Diagnosis in Our Hospital

Itoh¹,

Sugao²,

Chijiwa³

et al. 2010

Nihon Toyo igaku zasshi

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We surveyed side effect incidences with Kampo therapies in 2530 patients based on their Kampo diagnoses. The number of side effects seen, including taste disorder, was 569 in 503 patients. Side effects were noted in 64 (3.0 ) of 2139 patients administered Glycyrrhizae radix. The average 63.4 13.8 age of these patients was statistically higher than the overall 54.9 18.1 year mean. Symptoms which led to diagnosis of side effects were high blood pressure in 45 patients, edema in 16 patients, and hypokalemia in only 5 patients. Glycyrrhizae radix dose as an extract was 2.0 1.0 (mean SD) g/day in 34 patients, and as a decoction was 2.2 1.1 g/ day in 29 patients. There was no difference in administration or recovery periods between these two groups. Liver dysfunction was noted in 13 (1.0 ) of 1328 patients administered prescriptions containing Scutellaria radix. Scutellaria radix was administered as an extract at 2.3 0.5 g/day in 7 patients, and as a decoction at 2.8 0.8 g/day in 6 patients. Although there was no difference in administration periods, the 69.0 52.5 day recovery period from side effects in the extract group was longer than that of 22.7 16.0 days in the decoction group. Symptom improvement was had for a large portion of these side effects with the first visit, indicating that initial diagnoses were correct. Care should be exercised with regard to inducing side effects, with Kampo medicines, even when using traditional diagnostic standards.Scutellaria Radix, Glycyrrhizae Radix, liver dysfunction, side effects, pseudoaldosteronism

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Influence of Co-administered Drugs on Shakuyaku-kanzo-To Induced Hypokalemia

Cited by 4 publications

References 5 publications

Rhein 8-<i>O</i>-β-D-Glucopyranoside Elicited the Purgative Action of Daiokanzoto (Da-Huang-Gan-Cao-Tang), Despite Dysbiosis by Ampicillin

Rhein 8-<i>O</i>-β-D-Glucopyranoside Elicited the Purgative Action of Daiokanzoto (Da-Huang-Gan-Cao-Tang), Despite Dysbiosis by Ampicillin

Education Program of Kampo-medicine for Undergraduates in Preparation for Clinical Setting

Clinical Characteristics of Side Effects Induced by Administration of Glycyrrhizae Radix and Scutellaria Radix under the Therapy Based on Kampo Diagnosis in Our Hospital

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