The purpose of this study was to identify risk factors of drug-induced arrhythmia and drugs have a greater risk of causing it.From a search of the CARPIS (Case Reports of Adverse Drug Reactions and Poisoning Information System) database,which contains 43,000 case reports of adverse drug reactions,we obtained 251 cases of drug-induced arrhythmia which were assigned to a case group.We also selected 749 non-cardiac related adverse reactions at random and assigned them to a control group.Various data were compared between the case group and the control group and analyzed statistically.Comparing the 2 groups by means of logistic regression analysis revealed that the 4 patient background factors of woman post puberty (>18 years old),cardiovascular disease,hypokalemia and depression were associated with a significant greater risk of developing drug-induced arrhythmia.In addition,disopyramide,ritodrine,miconazole,halothane,thioridazine and sodium thiopental were found to significantly raise the risk of drug-induced arrhythmia.The findings of the present study should be helpful in preventing drug-induced arrhythmia and if it has already occurred,stopping it from becoming more serious.

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Cyclosporine (CsA) is considered to be a potential treatment for steroid-resistant nephrotic patients.The purpose of our study was to compare the pharmacokinetics and pharmacodynamics of CsA (microemulsion formulation,Neoral) between preprandial and postprandial dosing regimens in patients with refractory nephrotic syndrome.Twenty seven patients,who received Neoral once in the morning,were enrolled in this study.Neoral was administered to twelve and fifteen patients after (postprandial group) and 30 minutes before breakfast (preprandial group),respectively.Blood CsA concentrations were measured before (C₀) and 1,2,3 and 4 hours after administration of CsA (C₁-C₄).The value of C₁ in the preprandial group was higher than that in the postprandial group but the area under the concentration-time curve from 0-4 hours (AUC₀-₄) was not higher.While the values of C₀,C₁,C₂,C₃ and C₄ were correlated with those of AUC₀-₄ in the preprandial group,only the value of C₂ was correlated with AUC₀-₄ in the postprandial group.In the preprandial group,the rate of increase in serum albumin concentrations was significantly higher than in the postprandial group.However,the incidences of nausea and/or vomiting in the preprandial group were higher than those in the postprandial group.
In conclusion,our results suggest that preprandial dosing regimens of CsA are more efficient than postprandial dosing regimens,although gastrointestinal symptoms have to be considered.

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It has been reported that the patients with low manual dexterity,such as elderly patients,those suffering from rheumatoid arthritis (RA) or cerebrovascular disease with or without subsequent paralytic complications,are likely to have difficulty in opening medication packages.This is particularly so for pouch-form packages for powders which are designed to be torn open,an action that requires both hands.
In order to make an objective evaluation of the difficulty in opening medication packages,we first measured the actual strength required for the opening of a package called the strip pack (SP) using a special instrument.Next,we conducted a subjective sensory assessment of package opening for patients with cerebrovascular disease or RA,and studied the features that packages need to have to be opened by the majority of patients without serious difficulty.
We found that there was a correlation between the strength measurements made by the instrument and the results of the subjective sensory assessment.As our conclusion,packages could only be opened with relative ease by patients with varying degrees of dexterity impairment when the force required for opening was less than 11.4 N,and that a notch (small cut) in the package significantly aided package opening.

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Since it has frequently been observed that high serum levels of theophylline are difficult to control in children,we monitored serum theophylline concentrations in 868 patients,of which 322 received the drug as a continuous infusion.Generally,serum theophylline concentrations vary greatly among individuals and this is considered to be due to differences in clearance.
In this study,we investigated the relationship between age and serum theophylline concentration and theophylline clearance,finding that there was a weak association between dosage and serum concentration in all the age groups,which was not meaningful.Our results also suggested that theophylline clearance in children was greater than that in adolescents and adults,with the clearance in children in the 1-5 years (preschool) and 6-8 years age ranges being higher than that for patients in the 9-12 and 13-53 years age ranges.Our results suggested that the dosage should be determined based on theophylline clearance calculated with respect to age instead of on the standard value of 0.04 (L/kg/hr) given in textbooks.

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The Hikari Pharmacy worked together with the Department of Pharmacognosy of Tohoku Pharmaceutical University under an agreement on education and research between them to determine the properties of medicines in tablet and soft capsule form that a 74-year old female patient had taken and soon spat out.
On the request of the patient,we checked her personal drug profile and found that she had been taking vitamin D3 soft capsules,calcium L-aspartate tablets and mecobalamin tablets.By thin layer chromatography,we identified vitamin D3 for the soft capsule but could not detect calcium L-aspartate in the tablet by this method.We finally identified the substance as L-aspartic acid using an amino acid analyzer.We informed the patient concerning the medicines directly in a written form handed to her at Hikari Pharmacy.It only took a short time for the identification tests and the patient was satisfied with the results.
Performing identification tests for medicines is an important role of pharmacists in community pharmacies and thin layer chromatography is a good method for this purpose because it is simple,rapid and economical.

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Medication errors have been occurring when various liquids in containers resembling those for ophthalmic solutions are mistaken for eye drops.Usually,hospital-prepared ear and nose drops are put in containers used for ophthalmic solutions,and the formulation is indicated on the label.However,this makes ear,nose,and eye drops look quite similar outwardly and it is easy for the patient to use them for the wrong purpose.
Based on an examination of the containers and labeling of the different types of drops with respect to safety,we changed the container for the nose drops to an atomizer but we were not able to change the container for the ear drops.As a solution,we designed a“mark for prevention of misuse”and displayed it on the label.
To evaluate the usefulness of the mark,we conducted a questionnaire survey of outpatients.Fifty percent of the patients reported that they knew the effects of the drugs prescribed to them and 85% of patients responded that it was necessary to have“indications and effects”on drug labels.These responses suggest that indicating the effect of a drug is useful because it improves patients’ability to distinguish between drugs.Furthermore,eighty percent of the patients said that the“mark for prevention of misuse”was necessary.From the viewpoint of risk management,85% of the patients responded that it was a good idea to have the mark on the label.
The results of the present study indicate that the measures we adopted were effective.

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Uridine diphosphate-glucuronosyltransferase (UGT)1 A 1,a key metabolizing enzyme for the anti-cancer agent irninotecan (CPT-11),has several gene polymorphisms,one of them UGT1A1 *28 .In the United States,genotyping for UGT1A1 *28 is carried out in the clinical setting but not yet in Japan.In the present study,to develop the basis of a new pharmaceutical service in this regard,we developed a genotyping analysis procedure for 4 polymorphisms of the UGT1A1 gene (UGT 1 A 1 *6 ,*27 ,*28 and *60 ).The direct sequence method was used in genotyping,and simplification was achieved through the use of commercially available kits,and outsourcing sequencing to 2 outside laboratories.The genotyping of each polymorphism of UGT1A1 was independently carried out by two pharmacists and the results for 16 patients were identical to those obtained by the outside laboratories.The genotyping of UGT1A1 *6 ,*27 ,*28 and *60 conducted using our system cost less and was completed in a shorter period of time than that done by the 2 outside laboratories.The system we developed will be the basis of a new pharmaceutical service that will help achieve personalized medication.

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In order to prevent nausea and vomiting associated with cancer chemotherapy,5-HT₃ antagonists are widely used.However,we noticed that the incidence of constipation following the co-administration of anticancer agents and 5-HT₃ antagonists in chemotherapy seemed to be higher than stated in the package inserts.To investigate this further,we sent a questionnaire regarding constipation to patients who received cancer-chemotherapy at our hospital in which 5-HT₃ antagonists had been co-administered.We also investigated the degree of satisfaction of patients with the measures we took against constipation.
The incidence of constipation was high (68%) on the day of cancer chemotherapy in which 5-HT₃ antagonists were coadministered,or on the following day.The incidence of constipation without the co-administration of 5-HT₃ antagonists was 6%.Among patients who experienced loss of appetite after cancer chemotherapy,63% complained of constipation.There was a significant difference in the incidence of constipation between patients with loss of appetite and those with no loss of appetite.
We feel that the high incidence of constipation following cancer chemotherapy was caused by the combination of the 5- HT₃ antagonists and a decreased food intake.Among patients with loss of appetite,18% had difficulty in getting over the constipation and this suggests that the resulting lowered QOL could hinder the continuation of chemotherapy.We therefore consider that it is important to reduce adverse reactions in chemotherapy by administering preventive drugs thereby improving QOL.

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At Tokyo University Hospital,the Dispensing Techniques Seminar has been held regularly since September 1992 with the objectives of standardizing dispensing techniques and exchanging information.The participants are Pharmacy Dept and community pharmacy pharmacists.The seminar has been held once a month,with each course consisting of 3 seminars,to discuss the themes of“Prescription monitoring”,“Weighing out medicines”and“Medication consultation”.From 1995 onwards we conducted a questionnaire survey of the participants to continuously evaluate the content studied and the feelings of participants towards the seminar.More than 80% of the participants were satisfied with the content of the meetings.However,there was an increase in the number of people who felt that other content should also be studied,indicating a diversification of the needs of participants.We therefore felt there was an urgent need to cultivate lecturers who could handle a wider variety of themes to make the seminar more participation-oriented so that it can better meet the needs of participants and those of the current social environment.

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We designed a reporting system for the use of carbapenem antibiotics at Fuchu Hospital in order to restrict their use.We also examined the effect of the system on the number of vials of antibiotics used from December 2002 to November 2004 and compared the total amount of antibiotics used before and after introducing the system.
In our hospital,a large amount of panipenem is used,while the use of imipenem is limited.The antimicrobial use density (AUD) of panipenem decreased significantly from 9.85 to 7.59 due to the introduction of the reporting system (p<0.0citation=1)while that of imipenem decreased from 0.06 to 0.04.Therefore,the introduction of the system significantly influenced the use of panipenem but not that of imipenem.Following its introduction,the rate of occurrence of panipenem-resistant Pseudomonas aeruginosa decreased from 41.38% to 24.00% (p<0.00citation=1)while that of imipenem-resistant P.aeruginosa decreased from 18.23% to 10.91% (p<0.01).We therefore conclude that the reporting system brought about an apparent reduction in the occurrence of carbapenem-resistant P.aeruginosa .

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Increasing medical expenses have become a serious social problem so it is necessary for all medical staff,including hospital pharmacists,to conduct medical treatment from the viewpoint of economy.In this regard,we estimated the economic effect of checking prescriptions in outpatient antineoplastic chemotherapy between June 2004 and May 2005.Seventy three of 81 pharmacist inquiries resulted in prescription changes Twenty inquiries concerning changes to more appropriate drugs achieved cost savings of 454,633 yen and 19 inquiries,which probably prevented serious adverse events,were considered to achieve savings of 2,161,820 yen based on an evaluation using the Diagnosis Procedure Combination (DPC).These results suggest that pharmacists make a significant contribution to controlling medical expenses in outpatient antineoplastic chemotherapy as well as to making it more effective and safer.

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