In order to avoid adverse drug-interactions, we improved a computerized check system incorporated in the physician order-entry system. The improved system checks all drugs prescribed for a patient, including injections, and does not allow contraindicated combinations of drugs to be used. Our system also has a function for recommending safer substitutions for contraindicated drugs. In cases where contraindicated combinations are unavoidable, physicians may prescribe them by entering a password that is valid for one day only. The improved system can also evaluate the kinds of contraindicated combinations that physicians intend to prescribe. On checking our system's database, we found that there had been 299 contraindication alerts during 13 months for 589, 973 prescriptions. Also, the incidence of attempts to prescribe contraindicated drugs after clinical hours was almost 4 times as high as that during clinical hours. The contraindicated drug combinations were found in more than one type of prescription. Surprisingly, 80% of contraindicated combination events involved in injections and more than a half of contraindicated combinations were oral medicines with injections. We released alerts when requested by physicians when we judged these requests to be reasonable and 77 alerts were released during the 13-month period.
Thus, our computerized system, which checks drugs as physicians enter orders for them, should be extremely useful in ensuring medication safety. Our findings indicate the possibility that pharmacists are often unaware of the contraindicated combinations after physicians have ordered prescriptions, and also the desirability of pharmacists verifying drug interactions in patient medication histories.

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Sign language provides a basic level of communication for hearing-impaired individuals. Sign language, however, has rarely been used for communicating drug information and one possible reason for this is that there is no effective system for learning sign language related to drug information. In this study, we worked together with hearing-impaired individuals in developing a learning system for facilitating guidance on drug administration using sign language. First, information to be communicated by sign language was divided into 6 categories : 1) drug usage and dosage, 2) directions for use (external preparations), 3) allergy checking, 4) drug storage, 5) administration sites and 6) pleasantries to be exchanged with hearing-impaired individuals. Next, information to be conveyed under these categories was translated into sign language by hearing-impaired individuals and then we recorded the signing with a digital video camera and formatted it on to a digital video disc (DVD). Doing this made it possible for learners to review desired items of sign language repeatedly.
To evaluate the usefulness of our system, we had pharmacists complete a questionnaire which regarded 1) ease-of-use, 2) appropriateness of content and 3) efficiency for learning sign language. Their responses suggested that the system is a useful means of presenting sign language, has no time or place restrictions, and is easy to use, even for beginners.
If the system were incorporated in drug histories on DVDs, this would make it possible to give drug administration guidance by sign language using computers at pharmacies. The system may easily be shared by individuals or groups. We therefore consider that it is a useful tool for giving drug administration guidance to hearing-impaired individuals.

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We examined the influence of basic drugs and protein variants on the binding disposition of ropivacaine to α₁-acid glycoprotein (AGP). On doing this, we found the values of the competitive inhibition constant (K_i) for dipyridamole, verapamil, lidocaine and disopyramide with respect to the binding of ropivacaine to commercial AGP (70 mg/dL) to be 2.1, 5.2, 6.0 and 11.0μM, respectively. Also, there was a strong correlation between the f_u value and the AGP concentration when ropivacaine was added to plasma samples from ten healthy volunteers (r=0.861). Among the volunteers, eight showed F₁S variants and two showed F₁ variants without the S variant of AGP. There was no difference in the f_u value of ropivacaine between these two groups. However, when ropivacaine was added together with dipyridamole, the f_u values of ropivacaine in plasma from volunteers with ES variants were clearly higher than those from volunteers without the S variant. When ropivacaine was added together with disopyramide or lidocaine, however, there was no difference in f_u values between these variants.
Our results indicate that variability in the effectiveness and/or adverse effects of ropivacaine are caused by changes in f_u as a consequence of changes in AGP concentration. They also suggest that in combination therapy, it is also important to consider the AGP variant-dependence of the inhibitory effect of concomitantly administered drugs.

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Oral branched chain amino acid preparations consisting of three branched chain amino acids are used for the treatment of decompensated liver cirrhosis associated with hypoalbuminemia which occurs in spite of a sufficient intake in food. In order to evaluate the efficacy of oral branched chain amino acids, we investigated their effect in patients with liver cirrhosis, focusing on blood platelet levels. We analyzed the relationship between blood platelet counts and severity score, serum albumin concentration, total bilirubin concentration and prothrombin time.
Our subjects were 13 patients with decompensated liver cirrhosis (1 female and 12 males, mean age 60.8 years). In patients with blood platelet counts of more than 10×104/μL, serum albumin concentration and severity score were significantly improved by the oral administration of branched chain amino acids. On the other hand, total bilirubin concentration and prothrombin time were not significantly changed by orally administered branched chain amino acids in patients with blood platelet counts of more than 10×104/μL and also when they were under 10×104/μL.
These results suggest that classifying patients based on blood platelet levels might be useful in evaluation of the efficacy of oral branched chain amino acids, and doing this in addition to working out severity scores would be valuable in ensuring the proper use of oral branched chain amino acids.

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Recently, as the concept of self-medication has gained ground, there has been increased interest in nonprescription drugs and supplements. To ensure that nonprescription drugs are used effectively and safely, we developed a drug information database for such drugs with a drug interaction check system and used it to evaluate the drug information for ensuring the proper use of nonprescription drugs available in pharmacies. We conducted a survey of 1, 380 pharmacy customers regarding nonprescription drugs which targeted such subjects as prescription-nonprescription drug interactions, nonprescription-nonprescription drug interactions, contraindications, and precautions of nonprescription drugs. By doing this, we found that our database gave drug interaction warnings for 18 customers. Also, nearly 3% of the customers taking nonprescription drugs had diseases for which they were contraindicated, and 6.6% were subject to precautions. As a result, potential adverse outcomes (drug-drug interactions, disease-drug interactions, or duplication) could be prevented in 2.0% of the survey participants. Thus it seems that drug information on nonprescription drugs in a database like ours is very necessary in a pharmacy. Our findings suggest that the drug information recorded in our database would be useful in the prevention of medication-related adverse events and for improving the quality of life of patients. They also suggest that pharmacy customers need to consult a pharmacist in order to ensure that the nonprescription drugs that they purchase are the most appropriate for them therapeutically.

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Some medicines are known to decompose due to the influence of temperature, moisture, or light and the resulting deterioration in their quality may cause unexpected serious adverse reactions in patients. In this study, we exposed various forms of naftopidil to light and determined any changes in quality from their appearance, TLC and ¹H-NMR spectrum. The results showed that the degree of decomposition depended on the form of the drug, the wavelength of the light and duration of exposure to light.

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The influence on blood pressure of the combined use of tizanidine hydrochloride and fluvoxamine maleate was investigated in the Mie Chuo Medical Center. The average decreases in systolic pressure and diastolic pressure were 17.8 mmHg and 9.5 mmHg, respectively, these decreases in blood pressure being significant. The influence on blood pressure of other combinations was also investigated. These were tizanidine hydrochloride and paroxetine hydrochloride hydrate, another selective serotonin reuptake inhibitor (SSRI) which inhibits CYP1A2, and tizanidine hydrochloride with eperisone hydrochloride, which is metabolized by a CYP1A enzyme in the same family, and fluvoxamine maleate. Significant decreases in blood-pressure were not observed with these combinations so we consider that they may be used with comparative safety.

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We investigated patient use of the “Medicine-Pocketbook” at the Medical and Dental Clinic of the Health Sciences University of Hokkaido. An estimated 30% of our patients used Medicine-Pocketbooks, and 47% of these patients presented them to the pharmacy. In addition, 47% of the Medicine-Pocketbooks contained drug information coming from other medical institutions and pharmacies within the past six months. Although the use of the Medicine-Pocketbooks was still not widespread enough, our findings showed that they were being used effectively. We conducted several questionnaire surveys on the use of Medicine-Pocketbooks and received responses from a total of 298 patients, which we analyzed. The results showed that most of the patients did not know how to use the Medicine-Pocketbooks correctly. In view of this, over a period of two months we distributed leaflets on the correct use of Medicine-Pocketbooks to patients. This resulted in increasing the number of patients carrying Medicine-Pocketbooks to 40% and the number of these patients presenting them to pharmacies to 59%. Further, on examining Medicine-Pocketbooks, we noted several duplicated prescriptions and unfavorable drug interactions. From this study, we observed that Medicine-Pocketbooks play an important role in the risk management of drug therapy at the pharmacy and that instructing patients on the correct use of Medicine-Pocketbooks can decrease the risks involved in drug therapy.

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Interest in health has been increasing due to the current healing boom and frequent reports on the topic of health foods. We surveyed people in Yonago, Japan concerning alternative medicine and attitudes towards it using an unsigned, self-entry type questionnaire in order to clarify their understanding of alternative medicine, their use of it and ascertain the problems. Between April and June 2003, the questionnaire was given to 1, 913 men and women aged 20 to 82 years who resided or worked in Yonago City, of whom 1, 326 responded. Out of this number, the responses of 1, 245 (65.1 %) were valid and analyzed. The results obtained were compared among age groups.
Over 60 % of respondents were aware of the various kinds of alternative medicine and over 90 % of them had tried one form or another. Individual rates of use of alternative medicine, however, differed with age. As for means of treatment, 59.3 % used Western medicine only, 28.1 % used Western medicine together with alternative medicine and 12.6% used alternative medicine only.
In conclusion, when using alternative medicine together with Western medicine, people should ask their doctors whether the alternative medicine they would like to use is appropriate. Doctors should also ask patients whether they are using any alternative medicine. In the future, it will become more and more important for us to understand the purpose of alternative medicine and to use it responsibly on the basis of correct information concerning it.

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We developed a method for the determination of milnacipran in serum using a system combining liquid chromatography and mass spectrometry (LC/MS) in which electrospray ionization (ESI) was used. Milnacipran was extracted from serum by liquid-liquid extraction using an Extrelut^® NT 3 column. The chromatographic separations of milnacipran and amoxapine (internal standard) were performed using a XTerra^® RP 18 (150 × 2.1 mm I.D.) column with a gradient of 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The extraction recoveries at concentrations of 10 and 100 ng/mL were 85.6 and 83.7%, respectively. The calibration curve was linear in a concentration range from 5 to 300 ng/mL and the detection limit was 1 ng/mL. The intra-day and inter-a day assay precision expressed as coefficients of variation (C.V.) were 1.94-2.17% and 5.75-6.20%, respectively. This method proved to be useful in quantifying milnacipran in serum obtained from a patient who took this drug.

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