Latanoprost, a prostaglandin F2alpha analog (PG), has been shown to be an effective ocular hypotensive agent for treating glaucoma. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with PG. Timolol malate has been shown to be an effective ocular hypotensive agent when used alone or with CA inhibitor on glaucoma patients. However, the effects of latanoprost and timolol malate on CA have not been clarified. Therefore, we studied the effects of latanoprost free acid and timolol hemihydrate on human CA (hCA)-I and hCA-II using stopped flow method. Latanoprost free acid inhibited the hydration activity of hCA-I or hCA-II by a noncompetitive mechanism. Timolol hemihydrate activates the enzyme activities of hCA-I and hCA-II. In hCA-I and hCA-II, the enzyme kinetic results clearly showed that timolol hemihydrate increases the value of Vmax but does not influence the value of Km. The noncompetitive inhibition mechanism and the binding mode of latanoprost free acid indicate that the behavior of latanoprost free acid is similar to that of simple anions. Timolol hemihydrate has a heterocyclic moiety and secondary amino group, which are typical structures in efficient activators of carbonic anhydrase. Moreover, we compared the cost of lowering intraocular pressure (IOP) by 1 mmHg in the treatment of glaucoma. Latanoprost is less expensive for lowering IOP by 1 mmHg than other products. These data should be helpful in selecting topical ophthalmic solutions from the viewpoint of cost-minimization.
The purpose of this research was to examine whether the fatigue-relieving efficacy of a revitalizing medicinal product would be increased by counseling (advice to subjects regarding its expected efficacy), using both subjective and objective indicators. Twenty participants took the revitalizing medicinal product (drinkable product: 50 mL, once) on separate occasions, once with and once without counseling, with a 1-week interval. They completed a self-reported questionnaire (covering motivation, feeling of drowsiness, and general fatigue) and multi-dimensional fatigue inventory-20 (MFI-20) as subjective indicators, and blood flow in the inferior frontal cortex was evaluated by means of near-infrared spectroscopy (NIRS) as an objective indicator. The self-reported questionnaire showed that the revitalizing drink with counseling significantly improved general fatigue, as compared to the drink alone. MFI-20 showed no significant difference. Regional blood flow in the inferior frontal cortex was significantly increased by administration of the revitalizing drink with counseling, compared to without counseling (P < 0.05). Overall, the results indicated that counseling intervention increased the effectiveness of the revitalizing medicinal product.
Showa Pharmaceutical University introduced the vital-sign checks and physical assessment (VP) training program, which focused mainly on grasping normal conditions, in pre-training for clinical pharmacy practice in the second semester of the fourth year in 2010. Next year, the same VP training program and the additional training program, which includes grasping abnormal conditions, and an exercise based on a scenario were provided to the sixth-year students who could not have taken the VP training program in their fourth year. A questionnaire survey was conducted to evaluate these training programs both in the fourth- and sixth-year students. Both year groups of the students showed a generally high satisfaction of the VP training program, and felt that the degree of achievement after the program also rose greatly in all training items. Although six-year students who had experienced VP in the practical training in their fifth year answered a higher degree of achievement before the VP training program than those who had not, there was almost no difference between the two groups after the program. These results indicate that the VP training program achieved sufficient educational effects, irrespective of the year of the students and the experience of VP. As pharmacists require clinical ability and skills to make suitable clinical judgments, in a school setting we are planning not only to improve the VP training program but also to develop scenarios based on real cases in various clinical settings.
To examine the association between biologics for rheumatoid arthritis and serious infections (hepatitis B, hepatitis C, tuberculosis, pneumonia and sepsis), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of Pharmaceuticals and Medical Devices Agency (PMDA). The reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval. In addition, time to onset and age at onset of tuberculosis were investigated. Drug-reaction pairs were identified in both FAERS (n = 29,017,485) and JADER (n = 2,079,653). In both databases, significant associations were observed between biologics and infections (hepatitis B, tuberculosis, pneumonia and sepsis). JADER data revealed a significant association of etanercept with hepatitis C. In FAERS, the majority of tuberculosis events, associated with all drugs, were observed within 1 month of administration, whereas most tuberculosis infections associated with biologics were observed during the 5 months following administration. In JADER, most cases of tuberculosis associated with all drugs and with biologics, respectively, were observed during the 2 months after administration. In conclusion, hepatitis C associated with etanercept treatment should be closely monitored in clinical practice. In addition, tuberculosis associated with biologics should be carefully monitored for 5 months following drug administration. Further studies are needed to confirm these findings.
The frequency of adverse events with medication in an intensive care unit (ICU) is reported to be higher than that in a general ward. However, the pharmacist's intervention effect over the medical safety of drug therapy in ICU has not been fully evaluated. In this study, we examined the pharmacist's intervention effect on improvement in the safety of medication in ICU. We investigated medical safety interventions called “preavoid” performed by pharmacists in Saiseikai Yokohamashi Tobu Hospital's ICU from April 2011 to March 2013. The incidents and accidents discovered with the preavoid example were classified according to severity, and the intervention number according to severity was investigated. Among the 2158 pharmacist's interventions, there were 2060 preavoid examples, which is 95.5% of the total. Furthermore, 1915 (93.0%) of the preavoid cases were found before an incident or accident occurred, and in 145 cases, (7.0%) a disadvantage to patients was prevented from becoming serious. Moreover, a large number of incidents or accidents associated with pharmacist's intervention was classified as less severe, and there were no critical examples in which injury became permanent. In this study, we suggest that pharmacist's interventions improved the safety of drug therapy by avoiding disadvantages to patients before occurrence, and avoiding disadvantages that have occurred from becoming serious.
The relationship among dissolution profile, plasma nateglinide concentration profiles and blood glucose levels were investigated when administering nateglinide enteric coated granules just before feeding in normal beagle dogs. As compared with nateglinide immediate release tablets, the Cmax values of the enteric coated granules were lower than those of the immediate release tablets, and the Tmax values of the enteric coated granules became prolonged. In the case of 5.5 of dissolution pH value, both postprandial blood glucose level (PBG) and the fasting blood glucose level (FBG) tended to be decreased. As the dissolution pH value increased, especially more than 6.5, PBG did not tend to decrease. However, FBG tended to decrease. The effect of the amount of food on nateglinide plasma concentration was evaluated using enteric coated granules with 6.5 of dissolution pH value that mainly decreased FBG. As the amount of food increased, Cmax values became lower, and Tmax values became prolonged. The amount of food consumed is considered to have an effect on the nateglinide plasma concentration profile of the enteric coated granules, and also the FBG lowering effect. In clinical trials using nateglinide controlled release formulation containing enteric coated granules, it is considered important to note and evaluate the amount of food, the dissolution pH value and the dissolution rate at pH 6.5.
The purpose of this study was to investigate the influence of cigarette smoking on the risk of illegal drug abuse and self-medication, such as the proper use of pharmaceutical products, among high school students. An anonymous, self-administered survey was conducted before and after a lecture on the prevention of drug abuse in a high school located in eastern Hiroshima Prefecture in November 2011. The subjects were classified into three groups according to smoking behavior; non-smokers, former smokers, and current smokers. Significant differences were observed between groups. The rate of recognizing health damage caused by the abuse of stimulant drugs, narcotic drugs or solvents was significantly decreased in the cigarette smoking group. In addition, the rate of intent to use drugs that were considered to be “medications that enable them to stay up all night for days”, “medications that would allow them complete recovery from fatigue” or “medications that would improve their appearance” was significantly increased in the cigarette smoking group. The rate of prescription medication compliance, such as confirming their correct usage or following their prescribed usage was significantly decreased in the cigarette smoking group. An influence against illegal drugs and the awareness of the risks of self-medication were observed in non- and former smokers according to the questionnaire performed after the lecture, but the influence on the cigarette smoking group was minimal. Education promoting medication compliance may be necessary for high school students, especially students who abuse cigarettes.
Upper gastrointestinal symptoms, a common adverse effect of dabigatran, influence the continuation of medication. It has been speculated that this adverse effect can be reduced by changing the method of taking dabigatran: that is, to instruct patients to swallow dabigatran capsules whole with a glassful of water. However, there is no evidence to support this conclusion. Therefore, we changed our patient compliance instruction of dabigatran to the method mentioned above from September 2013 and investigated the effect of that change on the onset of adverse events and patient quality of life (QOL). Among 42 patients treated with dabigatran, 17 patients were categorized into the instruction change group and 25 were categorized into the no instruction change group. The Izumo scale was used to assess patient QOL. A total of 20 patients experienced side effects in the upper gastrointestinal tract (6 in the instruction change group, and 14 in the no instruction change group), and 18 patients in the lower gastrointestinal tract (3 in the instruction change group, and 15 in the no instruction change group). Izumo scale scores were significantly lower in the instruction change group than in the no instruction change group. Furthermore, in the no instruction change group, 5 patients showed a remarkable decrease in patient QOL by the adverse effects of gastrointestinal symptoms; however, in the instruction change group, this did not occur in any patients. The results indicate that patient QOL can be maintained by altering the method of taking dabigatran.