Pharmaceutical care for inpatients has been established as one of main duties of hospital pharmacists. It is therefore necessary to demonstrate the advantages of such care. Sasaguri Hospital has 3 different types of wards, one for the treatment of acute diseases, one for the longterm stay of elderly patients, and one for the provision of psychotherapeutic care. The percentage of inpatients receiving pharmaceutical care in the hospital has averaged about 99.6% of since October 2001. This report describes the results of such pharmaceutical care in Sasaguri Hospital. In 2000, the percentage of inpatients for whom drug information was offered from pharmacists to donors, was about 22% in the general ward for the treatment of acute diseases, but this rate was even higher in the other wards. In 2001, the percentages in the long-term stay and psychotherapeutic wards increased in comparison to the results of the previous year. The percentages of “pre-avoid” reports (pharmaceutical report of early detection of or avoidance of adverse drug reactions) among inpatients cared for by pharmacists in the general ward, the long-term stay ward, and the psychotherapeutic wards were 0.53%, 0.62%, and 0.42%, respectively. The number of “pre-avoid” reports increased with the increase in pharmaceutical care in all wards. These results demonstrate that appropriate pharmaceutical care is essential to ensure the adequate risk management of drug therapy. The number of insurance claims for pharmaceutical care per inpatient in the general ward, was smaller than that is the long-term stay or psychotherapeutic wards. In addition, the number of times that pharmaceutical advice was given to each inpatient per insurance claim in the general ward, was more than that in the other wards. Therefore, in the general ward, in order to increase claims for pharmaceutical care, it is necessary to step up the number of inpatients cared for by pharmacists, and to begin such care as soon as possible after admission. The percentage of inpatients for whom drug information was offered from pharmacists to doctors, the rate of prescription changes, and the number of “pre-avoid” reports during pharmaceutical care. showed no statistically significant differences between the short-term admission group and the long-term admission group in either the long-term stay or the psychotherapeutic ward. These results demonstrate that the necessity of appropriate pharmaceutical care in these wards is totally unrelated to the length of admission.
A curriculum was designed for a pharmacy school student completing a practicum at the pharmacy of the Neagari Municipal Hospital, a mid-sized hospital, and the practicum was carried out according to the curriculum. The curriculum was based on the criteria described in a medical educational manual and incorporated three factors, namely “Objectives, Learning Strategies, and Educational Evaluation, ” which together covered the educational processes. The time schedule was designed to be similar to that of typical work duties, thus enabling the student to experience real pharmacy practice. During the practicum, no exercises were omitted and we were able to implement, as requested by a doctor, modifications to the program. Accordingly, the quality of the practice was maintained, since each factor was based on a specific behavioral objective. The student's accomplishments were evaluated by the medical staff, including pharmacists and doctors, in order to reduce the individual instructors' burden as well as to maintain objectivity. By this manner of evaluation, not only were the achievements graded more objectively, but we could also evaluate the curriculum by comparing the evaluations of the instructors with those of the student. In conclusion, this curriculum is practical for small-and mid-sized hospitals accepting undergraduate pharmacy students and does not negatively influence the daily duties, while still maintaining the quality of the educational experience. This curriculum is simple to initiate and easy to modify. As a result, such a program is considered to be useful for other similar mid-sized facilities since it can help such institutions to promote efficiency in designing their own curriculum.
Information about safety greatly affects the decision by patients as to whether or not they will participate in clinical trails. Therefore, it is important to keep all participants fully informed. However, it is very difficult to manage information about adverse events that are reported during clinical trials, mainly because the amount of information is large and the casual relationship with investigational drug administration is often unclear. We sought to develop a method to effectively evaluate the clinical significance of reported adverse events and to also efficiently manage information. The adverse events reported to our institution by trial sponsors during the period between September 1999 and December 2001 were classified based on an evaluation of three factors : the degree of health hazard, the character (geographical location, previously known or new effect, clinical trial phase or post marketing phase), and causal relationship with the investigational drug. Based on the results of this analysis and a questionnaire survey of trial sponsors, we recommended that adverse events should be routinely categorized into three classes in the manner described above, and the dataregarding each event should be gathered in a standardized format, and electronic media should be used to transmit the data.
In recent years, medical treatment based on scientific evidence has increased in importance. The use of MEDLINE as a method of discovering such evidence is relevant because anyone can freely access MEDLINE via the World Wide Web (WWW). Unfortunately, few strategies to search for evidence by using MEDLINE interface (PubMed) have so far been reported in the literature. We therefore examined two PubMed search strategies to identify adverse reactions as follows : Method 1, which inputs the name of drugs and adverse effects, and Method 2, which inputs the name of drugs and adverse effects, including “adverse effects” and “etiology”. As a result, about 40% of all the literature identified by method 1 were noise. However, such noise decreased to about 20% with method 2. However, Method 2 could not identify some of the relevant literature available by Method 1. In order to search effectively for relevant literature, it is necessary to know the limitations of the search strategies.
Unlike conventional metered-dose inhalers (MDI), Fultide® is a dry powder inhaler for which a sufficient diffusion of the drug into the lung requires an inhalation rate higher than that for MDIs. In this study, we determined the inhalation rate, inhalation time and inhaled volume using a spirometer based on the instructions for inhalation provided by the manufacturers. We assessed the possibility of problems with the Fultide® Diskhaler® both in terms of the inhalation rate and the results of pulmonary function tests in elderly patients and those who had a poor pulmonary function. In addition, we checked the amount of the drug that remained in the blister in order to investigate how many times patients could inhale it completely. As a result of our investigation, we found that all patients in this study had a satisfactory inhalation rate of greater than 60L/min, which achieved sufficient diffusion of the drug into the lung. The inhalation rate did not change with age. In the pulmonary function tests, there was a significant difference between the asthmatic and COPD groups in %FEV1.0, but not in the inhalation rate. These results indicate that the Fultide® Diskhaler® can be useful even in elderly patients or in those with a poor pulmonary function. Regarding the number of inhalations required to completely empty the drug remaining in the blister, 90% of the patients were able to inhale the drug completely within three inhalations, regardless of their age and the type of disease. Accordingly, instructions for patients should stipulate the need to make at least three inhalations per blister.
It is well known that controlling the infusion rate is necessary, when administering total parenteral nutrition (TPN). We recently observed a significant reduction in the flow rate caused by several brands of TPN administration using Hicaliq® RF (HRF) mixed with total vitamin injection. In the present study, we investigated the flow rate reduction mechanism between several bands of TPN. The flow rate decreased in cases of TPN solution mixed with some vitamins for injection which contained lipophilic vitamins. These vitamins contained polyoxyethylene (20) sorbitan monooleate as a solubilizer of lipophilic vitamin. A reduction of the flow rate was observed in the TPN administration sets using an in-line filter which has a symmetric membrane structure, whereas the filter of the asymmetric membrane structure in the TPN administration set did not show a flow rate reduction. The lowest flow rate was observed in HRF, of all the TPN solutions used in the present study because 50% glucose in HRF showed a higher viscosity. There is possibility that an unstable flow rate was obtained in the case of a positioning failure of the TPN bag caused by the patient, when administering HRF mixed with polyoxyethylene (20) sorbitan monooleate containing total vitamins for injection.
We developed useful databases of cardiovascular agents to support the drug information service for patients, medical doctors and nurses. This system consists of six databases, including : 1) various information data about drug efficacies, cautions, warnings and contraindications, side effects, prudent medication, drug interactions, pharmacokinetics for 148 medicines, 2) relief information regarding disease state for cardiomyopathy and heart failure, 3) the search method to identify corresponding drugs from side effect data, 4) the mechanisms and the grade of drug interaction, 5) international mega trials regarding cardiovascular drugs, 6) connection with the information leaflets for patients already developed in our hospital. We are able to refer to information data by connecting these databases with each other on a notebook PC and thereby quickly provide accurate information.
Recombinant human granulocyte-colony stimulating factor (rhG-CSF) is administered either by intravenous drip infusion or subcutaneous injection depending on the indications. In the case of intravenous drip infusion, adsorption of rhG-CSF to the extension tube and infusion bottle can have an impact on clinical efficacy, since rhG-CSF is given at very small doses. In the present study, we attempted to determine the degree of adsorption of rhG-CSF [GranM300 (M300), Gran300 (G300), Gran150 (G150)] to extension tubes. The recovery rate of rhG-CSF changed a little with quality of the materials of the extension tube. In M300, when the length of a tube was 2 m and 4 m, the recovery rate of rhG-CSF was 89.4-91.0%, 82.6-89.1%, respectively. In G300, the recovery rate of rhG-CSF was 92.6-96.6%, 87.2-96.6%, respectively. In G150, the recovery rate of rhGCSF was 80.2-88.0%, 76.6-79.1%, respectively. From these results, it was suggested that the longer the tube, the greater the rate of adsorption. Moreover, the lower the concentration rate, the higher the rate of adsorption.
A fully automated high-performance liquid chromatography system with column-switching was evaluated to determine the concentration of zonisamide (ZNS) in human plasma. After the plasma sample was diluted to 10-times with the mobile phase, the sample (101μL) was injected into the column-switching system without pretreatment. ZNS was detected by ultraviolet absorption at 246 nm. The calibration curve of ZNS was linear and ranged from 1.57 to 50μg/mL of plasma. The coefficients of variation in the within-run (n=5) and the between-run (5 days) precisions of ZNS were below 5 %. The limit of quantification was 0.5pg/mL in 1 μL of human plasma. A good correlation was found between the data obtained by this system and the ELISA system using Markit-M Excegran (r=0.956) or the solid-phase-extraction HPLC method (r=0.985). This system for ZNS is thus considered to be a very useful measurement for therapeutic drug monitoring because of its high sensitivity, rapidity and low cost compared with other measurement systems.
Digoxin is often administered as a medication for congestive heart failure and heart rate control, and its therapeutic range has been reported to be 0.5-2. Ong/mL. However, compared with other medications, the margin between digoxin' s therapeutic range and toxic range is very narrow and it is necessary to monitor this drug therapy very closely. In addition, patients with an impaired renal dysfunction have a predisposition for developing digitalis toxicity. In order to avoid digitalis toxicity in such cases, we previously reported a simple index for the adequate administration dosage of beta-methyldigoxin according to varying degrees of renal function. However, our previous report was a simple index for the optimal dosages of beta-methyldigoxin when verapamil is not administered. In clinical cases, digoxin and verapamil are often co-administered for heart rate control, and we have observed the serum trough level of beta-methyldigoxin to be elevated due to drug-interaction. In order to investigate the influence of verapamil on the serum trough level of beta-methyldigoxin, we compared two groups of hospitalized patients : one group where verapamil was not administered (n=134) and another group where verapamil was administered (n=32). The results showed a correlation between creatinine clearance and clearance of beta-methyldigoxin in the two groups (the group not receiving verapamil : R2=0.51, p< 0.01 ; the group receiving verapamil : R2=0.46, p< 0.01). In addition, using a multiple regression analysis, verapamil was found to influence the clearance of betametyldigoxin. By this correlation, we build upon our previous findings and generated a simple index for the adequate administration dosage of beta-methyldigoxin based on variable degrees of renal function and the serum trough level of beta-methyldigoxin. These results indicate that by using our simple index, we can easily estimate the optimal dosages of betamethyldigoxin for patients who have variable degrees of renal function when verapamil is administered.
We examined the procedures for dispensing tablets or capsules that are not approved for crushing after checking the basis for such non-approval regarding 108 medicines introduced in our hospital. The problems are summarized as 1) a reduction in the pharmacological efficacy, 2) lowering the compliance due to a bitter taste or unpleasant odor, 3) dispersing hazardous powder, and 4) a disappearance of the efficacy of improved formulation such as for enteric coating. The taste of the ground tablets or capsules that are indicated to not be crushed was examined and compared with various concentrations of quinine hydrochloride powder in 8 healthy volunteers who showed a normal response to a bitter taste. Thirty-one out of 43 drugs were found to be tolerable to the taste, in which 13 drugs were less bitter than 0.5% quinine hydrochloride powder. However the other drugs either induced numbness or had a pungent taste and unpleasant odor, which were also considered to become the major reasons for nonapproval for crushing. Therefore, we found that several tablets have no serious problems, when they are dispensed after grinding. On the other hand, a number of hygroscopic medicines and anticancer agents tended to easily disintegrate in water. As a result, they can be prescribed by suspending them in water immediately before taking them. Our findings suggest that several tablets or capsules that are non-approved for crushing may thus be dispensed without any serious problems after crushing or disintegrating them in water. Therefore, our present findings may offer some useful information on the countermeasures for dispensing tablets and capsules that are not approved for crushing.
Since March 1995, counseling pregnant women about possible drug effects was started at the clinical Department of Obstetrics and Gynecology, in Niigata University Hospital, assisted by pharmacists. Regarding the counseling a pregnant women or women who have a high chance of becoming pregnant, information regarding the risk of congenital anomalies for various medicines and the choice of the literature information are the most important types of information. In order to provide information in the past, we examined reference manuals for available information on congenital abnormalities according to each category of medicine, and the compatibility of the respective information. We next analyzed the validity of the manuals depending on the drug information. We studied 625 drugs under their commercial names as requested by clinicians. Our findings show, as noted in parenthesis below, the results of 291 drugs under their product name. We examined 4 manuals and rated the drugs in each manual as follows : “Drugs in Pregnancy and Lactation (DPL)” Risk factors : A, B, C, D and X “Physicians' Disk Reference (PDR)” FDA-defined pregnancy risk factors : A, B, C, D and X “Prescribing medicines in pregnancy by The Australian Drug Evaluation Committee (ADEC)” The Australian categorization : A, C, B1, B2, B3, D and X “Drugs in Pregnancy : Toranomon Hospital (TORANOMON)” Drug evaluation : 0-5 points In each manual, we found drug information under commercial names and product name in 32.3-49.6% and 30.9-41.6%, respectively, and if we searched three manuals, finding the commercial names and product name increased to 57.4-71.1% and 50.9-62.5%, respectively. Our findings suggested that a combination of the available literature, using at least 3 reference manuals, was an efficient method for obtaining information on congenital anomalies.congenital anomalies.
In hospitals oil based ink is occasionally used to write the patient's name, his room number, and names of the drugs that are used in a mixture on the plastic containers used for infusion. This is done to prevent medication errors. In the current study, the effect of an oil-based ink on the infusion fluid was investigated. Using an oil-based ink containing xylene, letters and other characters were written on an infusion fluid container that was made of Polypropylene·Polyethylene·Ethylene vinyl acetate. It was confirmed that some xylene had been transported to the interior of the container (air phase). Furthermore, the xylene concentration in the air phase rose with repetitive writing and erasing, using the same oil-based ink. But no xylene was dissolved in the solution that was in the container (liquid phase). This observation convinced us that it is highly unlikely that the xylene in the ink can be infused directly into a patient's body. However, to assure the quality of the medication that is in liquid form, it is not desirable for a substance that does not normally exist as a component of the medication to move through its container. In the present experiment, physiological saline was used as a solution (liquid phase). Our findings showed that xylene had a high possibility of dissolving in solutions known for high xylene solubility (e. g., solutions with a large amount of amino acids or surfactants). Therefore, it is necessary to design a method to prevent ink from entering a container when an oil-based ink is applied to the outside of it.
The present situation of using injections prepared using the freeze-drying technique (FDI) was investigated by a questionnaire to nurses and pharmacists. From the results of the questionnaire, it appeared that their favorite formulas were FDIs prepared in glass vials because they are easy to handle and dissolve easily. The attached solvents to dissolve the FDIs were utilized by approximately 21% of the nurses. Adequate information about the solvents should be displayed on the body of the FDI's vials and their attached documents. The intervals between the dissolution of FDIs and the administration to the patients ranged from 30-60 min (36.7%). On the other hand, the attached documents recommended that they be “administered immediately following dissolution”. This suggested that the significance decreased on the attached document did not reflect their use in practice. Though “the method of dissolving”, “the stability of medicine after dissolving”, “the cure after dissolving” and “the stability of the FDIs 's themselves” were cited as being frequent questions by the nurses, the descriptions about these items on the attached document were insufficient. The queries concerning FDIs to the pharmaceutical companies were mainly about the container and/or the FDIs, the changes in property of the FDIs, the admixture of foreign matter into the FDIs or the method of dissolution. The origin of the queries were due to both the accidents during the manufacturing process and the misuse of the FDIs by nurses. In order to improve the rational use of injectable drugs, improved information provided by the attached document for FDIs is recommended.
Tacrolimus is widely used as an immunosuppressive drug. For the best clinical outcomes, it is important to keep the blood concentration constant. Tacrolimus is continuously infused using polyvinyl chloride (PVC) tubes for patients undergoing hematopoietic stem cell transplantation in the Department of Pediatrics of Okayama University Medical School. This method causes a fluctuation in the patients' blood concentrations. We found that it was difficult to maintain a constant blood concentration. We assumed that their blood concentrations were affected by the absorption of tacrolimus by the PVC tubes. In this study, we showed that a large amount of tacrolimus was absorbed by the PVC tubes and that changes in the patients' blood concentrations were caused by the absorption of tacrolimus by the PVC tubes. We clarified that tacrolimus was not absorbed by polybutadiene (PB) tubes, and the patients' blood concentrations were well controlled by PB tubes. Regarding risk management, our findings suggest that the tubes which do not absorb tacrolimus, should be selected when administering continuous infusion of tacrolimus.
Cardioplegic solution (CPS), a pharmaceutical product manufactured at our hospital, is used for operative myocardial protection. Glucose, one of the elements of CPS, is known to disintegrate into formic acid, levulinic acid and 5-Hydroxymethylfurfural (5-HMF). Accordingly, the stability and their shelf life of CPS were evaluated by pH variation, visual inspection and the amount of 5-HMF. CPS was preserved for 12 months at room temperature (25°C) and at 4°C (under room light or in darkness) after autoclaving at 115°C and 0.7kg/cm2 fo 30 min. The pH of the sample was observed along with a periodical visual inspection. The amount of 5-HMF in the CPS was determined by high-performance liquid chromatography (HPLC) with an UV detector at 284 nm. It was found that light had no effect on the production of 5-HMF. The amounts of 5-HMF in the samples preserved at 25°C tended to be greater than those in samples preserved at 4°C. However, it seems that the CPS was relatively stable since the amount of 5-HMF in the CPS was less than 1/40 of the limit noted in the fourteenth revised edition of the Japanese Pharmacopoeia (JPXIV). These findings suggest that a temperature of 4°C is preferable to 25°C for the preservation of CPS and that the CPS remains relatively stable for more than 12 months.
We herein report a case in which insulin was added to a high-calorie infusion preparation administered for 7 days to patients with HPN. In our previous study, the residual ratio of insulin was measured based on the formula ; Hicaliq® solution-No.2 (700mL) +Proteamin® 12X (200mL) + 10% NaCl (20mL). As a result, the residual ratio decreased daily until the 7th day. In the present study, the residual ratio of insulin was measured in the infusion bags and the drip solution of other high-calorie infusion solutions ; Unicaliq® N and Aminotripa® No.2. The residual ratio of insulin in the drip solution of Unicaliq® N began to decrease gradually from the 3rd day, and it decreased to approximately 71 % on the 7th day. In contrast, there were no successive decreases in residual ratio of insulin during the 7day period in either the infusion bags or drip solution of Aminotripa® No.2. The residual ratio was constant at approximately 85%. In other words, with Unicaliq® N, as with Hicaliq® solution-No.2, the residual ratio of insulin decreased due to a decrease in the daily insulin titer. Based on these findings as determined using the above formulas, the control of blood sugar level may be hindered on the 5th day and thereafter. Conversely, with Aminotripa® No.2, the residual ratio of insulin did not decrease for 7days. Therefore, Aminotripa® No.2 seems to be the most appropriate formula among the three evaluated ones for the high-calorie infusion in patients undergoing HPN, when the stability of insulin is regarded as important.
Due to an ever growing awareness of health, there has recently been an increased interest in healthfoods. However, this development is also connected with many problems, including possible interactions between healthfoods and pharmaceuticals and reports of healthfoods being found to contain pharmaceutical substances. As a result, we undertook a survey of the situation regarding healthfoold use among hospital inpatients and also investigated helthfood websites on the Internet. The survey of healthfood use showed that around half of hospital inpatients had previously used healthfood with no variations between the sexes or age groups ; around 30% used healthfoods during their hospital stay. However only 4% of the patients had been asked by medical staff members regarding whether they used healthfoods. Most pharmacies named manufacturers and websites as their source of information on healthfoods. In our survey on the sale of healthfoods over the Internet, in January 2001, before the introduction of standards on the labeling of nutritionally functional foodstuffs, we found that only five out of 25 websites dealing in foodstuffs containing St. John's wort displayed a warning notice (e.g. regarding the side effects and interactions). Six of the 25 sites gave details on the drug usage and permissible dosages. In June 2002, after the introduction of standards on nutritionally functional foodstuffs, we found that 13 of 44 sites displayed a warning notice on St. John's wort and 24 of the 44 had information on the method of use and permissible dosages. Our survey revealed that although one-third of all patients receiving medical treatment were using healthfoods, the levels of awareness among the medical care staff were low. It also becameclear that it is difficult for ordinary consumers to obtain accurate information from the Internet or other sources. In the future it will be necessary for pharmacists, who are supposed to be pharmaceutical specialists, to work together with other medical care professionals to obtain and supply accurate information on healthfoods as well as pharmaceuticals to patients.
The patient, a 56-year-old man with chronic renal failure (CRF) who had been receiving hemodialysis 3times a week, developed aplastic anemia. He was treated with antithymocyte globulin (ATG), which was administered on the days when he was not scheduled for hemodialysis. No specific adverse reaction in his renal functions was noted that could be attributed to ATG. Thrombocytopenia persisted despite frequent platelet transfusions, thus indicating refractoriness to this therapeutic modality. The patient died on Day 43 due to complications before the effect of ATG became apparent. As a result, the efficacy of ATG therapy for aplastic anemia could not be evaluated in this patient. However, the results of this therapy suggested that ATG could be safely administered even to patients receiving hemodialysis for CRF.