After surgery, blood pressure tends to increase due to psychological and physical stress, such as anxiety and pain. In patients with hypertension and cardiovascular disease, this increase in blood pressure is more marked and sometimes leads to serious systemic complications. Therefore, the need for careful attention to postoperative blood pressure management to prevent complications following surgery has been recognized. In the present study, we investigated whether a nitroglycerin patch and the sublingual administration of nifedipine were effective treatment modalities for the management of postoperative hypertension and also evaluated their usefulness. Twenty-nine patients who developed postoperative hypertension after digestive tract surgery were studied.
The results obtained were as follows.
1. From 2 to 12 hours after the administration of a nitroglycerin patch, the systolic blood pressure decreased significantly. However, 54 % of the patients demonstrated a systolic blood pressure of greater than or equal to 180 mmHg after the administration of nitroglycerin patch.
2. The sublingual administration of nifedipine caused significant decreases in the systolic blood pressure, diastolic blood pressure and mean arterial pressure.
3. As a result of the multiple regression analysis, the mean arterial pressure after administration of nifedipine showed negative correlation with dose of nifedipine and age, while the mean arterial pressure before the administration of nifedipine are positively correlated.
As a result, the use of a nitroglycerin patch was not found to effectively control blood pressure. The sublingual administration of nifedipine, however, was found to effectively reduce blood pressure. These findings may have important clinical implications in the management of postoperative hypertension.

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In order to clarify the binding site of drugs on human serum albumin (HSA), competition studies were carried out using ELISA for glycyrrhetic acid (GA), which is mainly bound to the diazepam site on HSA.
The release of GA from HSA was detected as a displacement by the various drugs [bezafibrate (B), delapril HCI, diclofenac Na (D), doxifluridine, famotidine, ibuprofen (I), loxoprofen Na (L-1) and its metabolite (loxoprofen Na trans-OH (L-2)), pravastatin Na]. The percentages of GA release by the addition of I, D, L-1, L-2, which belong to nonsteroidal anti-inflammatory drugs, and B were 96.0%, 86.5%, 25.4%, 25.6% and 12.6% respectively. In addition, the percentages of GA release by addition of the other 4 drugs ranged between 3. 2 and 4.1%. These results showed that I and D were strongly bound to the diazepam site, while the binding of L-1, L-2 and B was weak. Thus, L-1, L-2 and B may predominantly bind to other site (s) on HSA.
Therefore, ELISA for GA was suggested to be helpful for studying the binding site (diazepam binding site) of the drugs on HSA.

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After adding insulin into high-calorie infusion, we measured the residual ratio of insulin which had been administrated daily until the 7 th day, and analyzed the blood sugar levels of the patients.
As a consequence, insulin adsorption to infusion bags, infusion lines, and final filters decreased the residual ratio, which had become stable under saturation and these findings correlated with those from earlier reports. However, following the 3 rd day, due to a decrease in daily insulin titer, a decrease in the residual ratio was again noticed. On the 7 th day, the residual ratio in the drop of both the multiple vitamin added group and non-added group was 77.9±4.6% and 73.7±5.9%, respectively. On the other hand, the blood sugar level of patients tended to increase according to the dates before administration. Furthermore, an inverse correlation was found between the blood sugar level and the residual ratio of insulin, which thus suggested the possibility that a decrease in the residual ratio of insulin accompanied a daily increase in the blood sugar level of the patients, which thus results insufficient blood sugar control.
Therefore, when adding insulin into high-calorie infusions, a daily analysis of the residual ratio, as well as improvements in the TPN (total parenteral nutrition) design, such as a gradual increase in the amounts according to the date of administration, are thought to be requited.

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In Nagoya City University Hospital, a two-week training program for senior students in pharmacy training was carried out up until 1999. The large majority of senior students took a passive role in this pharmacy training course and therefore did not understand that importance of such training. Therefore, the pharmacy training period was extended from two-weeks to four-weeks in 2000. We thus evaluated what differences there were after the training was increased from two-weeks to four-weeks.
The four-week training program was found to increase student motivation toward the pharmacy training. Our survey concluded that approximately 69 % of all senior students were interested in pharmacy training and 75% of senior students understood the role of the pharmacist. In addition, 87% of senior students had an improved image of pharmacists after the new pharmacy training. The reason for such an increase was that the senior students gained a better understanding of the reasons for training and also obtained practical experience in pharmaceutical care. These findings suggest that the four-week training program with self-learning exercises was useful for normally passive senior students. It also enabled hospital pharmacists to make an even greater contribution to the pharmacy training program.

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Levofloxacin (LVFX) is a rapidly absorbed new quinolone and (S) - (-) -ofloxacin. The effects of metal cations on the urinary excretion of Levofloxacin (LVFX) were investigated in five healthy volunteers at the time of differential administration by measuring the unmetabolites of LVFX in urine and the findings of LVFX were then compared with those of long-acting Sparfloxacin (SPFX). Magnesium oxide (MgO) containing Mg²⁺ and sucralfate containing Al³⁺ are examined as metal cations.
Urine samples were collected for 10 and 24 hours after a single oral administration of LVFX and SPFX, respectively. The unmetabolites concentrations of LVFX and SPFX in urine were determined using HPLC.
The urinary excretion of LVFX decreased significantly after the simultaneous administration with MgO and sucralfate and at 1 hour after the administration of LVFX (p<0.05) but was not affected at 2 hours after administration. The administration of MgO and sucralfate within 2 hours after the administration of SPFX resulted in a significant decrease in SPFX urinary excretion (p<0.05). However, the decrease in SPFC urinary excretion was less than that in LVFX. Sucralfate decreased the LVFX urinary excretion more than MgO although the difference was not significant. The effect of sucralfate on SPFX urinary excretion was the same as that for MgO.
These results suggest that the interactions between LVFX and metal cations are avoidable by the administration of metal cations at 2 hours after the administration of LVFX and the administration of metal cations must be avoidable within 2 hours after the administration of SPFX.

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We examined the utility and reliability of data consisting of general information about drug characteristics, contraindications and adverse drug reactions (ADRs) in drug guidebooks which are available to patients in bookstores.
The information for patients written in five drug guidebooks describing prescription drugs was compared with those available in package inserts. The descriptions about warnings were also compared with those on respective package inserts of the drugs themselves, to determine whether the documentation was appropriate.
About 9, 000-10, 000 drugs are contained in these books, with revision being made almost every year. Relatively cheap prices allow easier access of patients to these books. Out of 61 drugs with provisions on warnings, 35 drugs partially or completely lacked an adequate description about the warnings. Approximately 70% of these warnings were related to serious ADRs. These were some insufficient examples in terms of explanations about the warnings (For example, the initial symptoms of the ADRs were either not described or ADRs were explained with medical terms.).
As a result of comparing drug guidebooks specific for patients, the number of drugs included, the frequency of revision and the prices are all considered reasonable. It is conceivable that the utility of these drug guidebooks would be greatly improved if the headlines for every descriptions of drugs are more detailed. As for drugs with a potential to induce serious ADRs, the initial symptoms should be described using simple words so that patients can understand them easily, whereby the patients themselves can easily perceive signs of ADRs even at early stages. In addition, adequate guidance is required to cope with the onset of initial ADRs, for example, recommending a prompt discontinuation of drug administration followed by consultations with physicians.

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It is assumed that national hospital has a responsibility in cancer treatments as one of policy-based medical services. A new systematic approach for the administration of cancer treatment was developed to improve clinical pharmaceutical services by introducing pharmaceutical care in cancer surgical wards.
This treatment approach was based on recent similar treatment programs in the U.S.A. regarding cancer pain control, pharmacological nutritive management, the monitoring of adverse reactions due to cancer chemotherapy and evaluation of order-made cancer chemotherapy by a team from Osaka University Hospital.
A data analysis based on previous scientific research including order-made cancer chemotherapy with pharmacists as leaders could improve the overall medical treatment performed by such teams.

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Due to an emergency warning from a pharmaceutical company, we evaluated the procedure of providing drug information to medical staffs. The warning was made regarding DEHP, which is a plasticizer of PVC eluted in etoposide injections, and intravenous transfusion sets made from PVC are used in such injections. We tried to determine whether or not any leaching of DEHP occurred during etoposide injection. Moreover, we investigated the properties of DEHP, the mechanism of DEHP leaching from PVC, and also inspected other medicines that may also have leaching of DEHP in PVC administration sets. As a result, no clinical evidence was found to support this urgent notice. However, passing through several years, related information became gradually clear. Therefore, in the information asked for quick offer, it was suggested that gradual and continuous information service becomes indispensable especially.

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Di-2-ethylhexyl Phthalate (DEHP) was reported to dissolve from a polyvinyl chloride (PVC) administration tube during the infusion of an injection fluid containing a solvilizing agent, soybean oil or lecithin, etc. This paper describes the behavior of DEHP dissolution from PVC tubes during enteral tube feeding. The DEHP concentration was determined using HPLC. After the passage the ENSURE LIQUID^® (EL) solution through the PVC tube, DEHP was dissolved in the EL solution. The EL solution is one type of enteral nutrition. This dissolution pattern was similar to that of injection fluid containing a solvilizing agent, in which the DEHP concentration in the EL solution increased linearly over time at first and thereafter reached a plateau. 170 μg of the DEHP was dissolved after 200mL of the EL solution had passed through the PVC administration set (the drip conditions were 25°C, 100mL/hr, tube length 115cm and inner diameter 0.3cm). The amount of DEHP which dissolved into the solution depended on the temperature (25-40°C), and no clear difference was observed between the PVC tubes (administration tube, feeding tube). In addition, the amount of DEHP that dissolved into the solution varied depending on the type of enteral nutrition.

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A drug can cause several adverse reactions and the known effects are listed in the Package Inserts. Ordinarily drug therapy is performed by poly-pharmacy, and co-administered drugs in a prescription may have same adverse effects. Since overlapping of adverse effects might increase the possibility of adverse effects, we investigated such actual overlapping using computed data of about eighty thousand instances of medical treatment per patient.
Overlapping was found in about half of all prescriptions including two or more orally administered drugs and the mean value of 3.4 adverse-effects-overlapping per prescription were observed. Frequent overlapping adverse effects were acute circulation failure, Stevens Johnson syndrome, agranulocytosis, toxic epidermal neclosis, liver abnormalities and so on..It is found that seven distinct drugs demonstrate the same adverse effect in one prescription.

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The development of drug information on prescribed medicine using a “medicine-pocketbook” was evaluated as one of the methods for drug information offered due to the revision in the medical treatment fees and pharmacy remuneration that went into effect in April 2000. The patients need to carry and present a medicine-pocketbook to the medical institution and pharmacy, and fill in the points personally noticed in the pocketbook to prevent the occurrence of side effects and duplicated prescriptions, which are the main purposes for this medicine-pocketbook. We conducted a questionnaire survey of patients to discover the possession and usage of this medicine-pocketbook. We analyzed the answers of 737 patients. It appears that 73.1% of the patients using our pharmacy possess a medicine-pocketbook. In spite of that, only 18.4% and 11.5% of patients claimed to have presented it at the hospital and other pharmacies, respectively. Finally, 36.5% of patients feel that such a pocketbook is useful. We have to explain the usage and advise the patients so that they can better use the pocketbook at other medical institutions and pharmacies, and this will lead to the prevention of side-effects and duplicated prescriptions. In addition, medical institutions and pharmacies need to promote the usage of the medicine-pocketbook vigorously in order to share information about the patients.

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To investigate the description of the expiration date and manufacturing number on the drug packages, “pillow” packages and “heat-seal” packages, the questionnairing was carried out to pharmaceutical companies. Fifty-six drugs consisting of three hundred thirty-seven items, with sales of over 10 billion yen in 1998, were investigated at the corresponding 26 companies. The recovery rate of the questionnaire from the company was 100%, and the answer for all questions was also perfect. Three hundred fourteen items (93%) have had description regarding the manufacturing number and/or the expiration date on the heat-sealed packages. The manufacturing number took precedence over the expiration date. Of 269 pillow packages, 69 items (26%) have had description of manufacturing number and/or expiration date on the pillow package. There were 41 products (12%) that the company did not guarantee an expiration date being described on the box container when the packages were taken out from the box container.
As a result, the description of the manufacturing number and expiration date on the packages, “pillow” and “heat-seal”, is still not complete even though the companies guarantee the expiration date when the drugs were stored with these packages. Since the information of the expiration date is necessary for the appropriate management of tablet and capsule products, it is required to describe manufacturing number and expiration date on every drug package including “pillow” and “heat-seal” packages.

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The stability of powdery dosage forms of drugs prepared by unsealing the packages was investigated. For 247 articles purchased by the Yamanashi Medical University Hospital, the variables related to the evaluation of stability after unsealing these packages and investigating the contents based of an “Interview Form”. A longterm preservation test was carried out on 153 items (94%), and the mean length of the test was about 36 months. The acceleration and the severity tests were carried out using 17 items (10.4%) and 114 items (69.9%), respectively. The mean conditions of the acceleration test was 40°C/6 months, which agreed with the guidelines proposed by the “Drug Manufacturing Guidelines”. On the other hand, for the severity test, certain conditions for the evaluation could not be arranged, and testing was carried out under various conditions. In order to improve the efficiency of dispensing and the quality of life for patients, a further increased standardization of the testing conditions is recommended.

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A four-week practical hospital training course for undergraduates at Takarazuka Municipal Hospital has been conducted since 1998. The curriculum at our hospital consists of three elements, i.e., lectures on hospital pharmacy, the dispensing service and the clinical pharmacy service. Regarding the clinical pharmacy service, a case study had token a long time for the purpose of learning the actual services. In this study, we compared the results of the new curriculum with those of previous curriculums to establish a more effective and practical curriculum for undergraduates. Our curriculum showed no significant difference with the findings of other reports. Next, we investigated the student' s awareness by questionnaire. The results showed that most students developed on increased awareness of the pharmacist' s daily practice by the end of the practical training course. However it also showed a tendency that their interests in pharmacy practice differed according to their future courses and the university they were studying.
From these results, further progress therefore appears to still be obtainable by increasing the cooperation between pharmaceutical universities and hospital pharmacies. In addition, it was considered that our curriculum should be further improved by better meeting the needs of students during the practical training course.

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