The events following drug administration can be divided into two phases: a pharmacokinetic phase (PK) and a pharmacodynamic phase (PD). The pathophysiologic status of patients or concomitant drugs can affect both the PK and PD of a drug. Therefore, it is important to distinguish the effects of several diseases or drugs on the PK from those on the PD. Based on this concept, we studied the mechanism and risk factors of adverse drug reactions using PK-PD analysis. This review summarizes our findings: 1.Renal failure with severe hypotonic hyponatremia is associated with increased central nervous system sensitivity to cephalosporin-induced seizures. 2.Isoniazid potentiates the sensitivity of the central nervous system to cefazolin-induced seizures, and the increased sensitivity is associated with the inhibition of vitamin B6 metabolism by isoniazid. 3.Moxifloxacin can induce histamine release, leading to an increase in serum epinephrine concentrations and hyperglycemia. 4.Hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination. 5.There was large interindividual variability in not only the PK of sunitinib but also the PD of sunitinib-induced thrombocytopenia. These findings provide useful information for the prevention and management of several adverse drug effects.
Therapeutic drug monitoring (TDM) is an essential tool for the optimal use of drugs. Although rare, the drug concentration in blood determined by TDM can be higher or lower than that predicted from the dosage amount and patient information. In such cases, it is necessary to consider the occurrence of false positives and false negatives in the measurement process. Dose adjustment based on the measured blood drug concentration poses potential risks of underdosing and overdosing in patients suspected of false positive and false negative data, respectively. Therefore, pharmacists involved in TDM are required to become familiar with false positives and false negatives in TDM. In particular, the possibility of false positives in TDM of immunosuppressants by the affinity column-mediated immunoassay (ACMIA) method should be considered, while TDM of vancomycin or phenytoin requires attention to false negatives during measurement by the particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method. Moreover, interference from IgM in the measurement process may be of concern in false-negative results; therefore, the measured blood drug concentration needs to be verified when the blood IgM level is high. This mini-review outlines false positives and false negatives that should be considered in TDM and presents a discussion of the relevant literature.
In 2012 we conducted a questionnaire survey to clarify the current state of pharmacy-related universities and clinical faculties and identify problem areas in pharmacy education and research. The survey was sent to 74 universities nationwide; responses were received from 488 out of 530 faculties distributed at 59 universities. The male/female ratio of the respondents was 3:1 and the age breakdown was 24% aged 30-years or younger, 61% aged 40-50-years. Regarding interest in education and research, 62% of the respondents emphasized education over research; the weekly average time devoted to these respective activities was 21 hours for education and 13 hours for research. Of the respondents, 46% had not even practiced once in 2012, while 61% out of the responders who had practiced (52%) had engaged in practice in a clinical setting one day per week or more. As for research, 83% and 20% of respondents supervised undergraduate and PhD students, respectively. Despite the fact that roughly half of all respondents do not fully engage in practice and research, satisfaction with the current situation on a 5-point scale was 35% for “satisfied” and “somewhat satisfied” combined, and 40% for “acceptable.” Clinical faculties should not be content with the present situation and should strive to advance education and research by enhancing motivation to train the next generation. It is hoped that future discussions will lead to the revitalization of practice/education/research among clinical faculties, and also to the training of staff in clinical faculties, in whose footsteps the pharmacy students and/or next generation pharmacists can aspire to follow.
The aims of the present study were to evaluate whether the postulated H+/tertiary amine antiporter is expressed in human intestinal HT-29 cells as well as other cell lines, Caco-2 and LS180, and to identify the factor(s) of the uptake activity of the postulated H+/tertiary amine antiporter in the intestine. The profile of extracellular and intracellular pH-dependent uptake of quinidine, a substrate for the postulated H+/tertiary amine antiporter, into HT-29 cells was consistent with that in Caco-2 and LS180 cells. In addition, the uptake of quinidine into Caco-2, LS180, and HT-29 cells was significantly inhibited by diphenhydramine, a potent inhibitor of the postulated H+/tertiary amine antiporter, suggesting that the postulated H+/tertiary amine antiporter may be expressed in HT-29 cells. The diphenhydraminesensitive uptake (Δuptake) of 12 cationic compounds (celiprolol, acebutolol, pindolol, bisoprolol, metoprolol, propranolol, procainamide, quinidine, flecainide, clonidine, pyrilamine, and verapamil) into LS180 cells was positively correlated with their lipophilicity (Log D) values. In addition, there was a moderate negative correlation between the Δuptake of cationic compounds and their Log polar surface area (PSA) values. The predicted Δuptake values estimated by the Log D and Log PSA values fitted well with the observed values. These findings suggest that the lipophilicity and PSA of cationic compounds are factors of the uptake activity of these compounds by the postulated H+/tertiary amine antiporter in the intestine.
It is desirable for pharmacists to confirm the laboratory data of individual patients before dispensing. However, it is difficult to dispense prescription medications after checking individual laboratory data for all patients due to time constraints. To assist in prescription audits, Shinshu University Hospital began including laboratory data on in-hospital prescriptions in April 2011. This study examined the impact of laboratory data included on in-hospital prescriptions on prescription questions. The contents of prescription questions after the inclusion of laboratory data on in-hospital prescriptions (October 1 - December 31, 2013) were compared with those before inclusion of laboratory data (October 1 - December 31, 2010). The rate of prescription questions was significantly higher after compared with before the inclusion of laboratory data (2.30％ vs 2.04％, respectively; P = 0.020). In particular, the number of prescription questions referring to laboratory data showed a 3.5-fold greater increase after the inclusion of laboratory data on inhospital prescriptions (P < 0.001). Prescription questions referring to laboratory data included on prescriptions were associated with a prescription revision rate of 65.6％. Prescription questions referring to laboratory data involved clarification of the doses of medications, such as levofloxacin and famotidine, in patients with impaired renal function. These results indicate that the inclusion of laboratory data on in-hospital prescriptions is useful for efficiently extracting those requiring clarification.
Team medical care needs to be improved at the outpatient clinic to manage highly complex cancer chemotherapy. In May 2008, Kurashiki Medical Center was the first medical institution in Japan to start a pharmaceutical outpatient clinic called a “support clinic.” At the support clinic, oncology pharmacy specialists interview patients and propose several suitable options of drug regimens to the physicians to ensure safe and effective treatment. We evaluated the functions expected of the support clinic and the appropriateness of health insurance application to the clinic's services. Physicians and nurses highly evaluated the work of the oncology pharmacy specialists at the support clinic. The function that they expected most of the support clinic was the design of supportive therapies followed by the design of treatment strategies. All 93 patients surveyed said that the support clinic was beneficial to them. Ninety-six percent of the patients considered that the support clinic services were worth paying. The support clinic has been providing oncology pharmacy specialists with great opportunities to fulfill their potential. Its services are needed by medical professionals and patients who want improved outpatient cancer treatment.
We conducted a home medical care (HMC) training workshop consisting of presentations given by regional HMC leaders that targeted community pharmacists in collaboration with a nearby pharmaceutical association. Subsequently, we conducted a questionnaire survey with the pharmacists in attendance to assess their opinions of the present HMC situation. The participants' satisfaction with the workshop was relatively high, at an average of 8.13 out of 10. Among the participants, 70.9% had experience with HMC, such as visiting pharmacy services at patients' homes, with the most frequently practiced activity being “drug administration guidance for patients at home.” However, activities such as “accompanying medical rounds” and “participation in home care conferences” were not widely practiced (at a rate of less than 50% of the most popular activity) among the participants. Next, many participants responded that the key HMC factors were the creation of systems of cooperation between different professionals and their environmental arrangements. Participants also made suggestions for future lectures, such as on the subjects of contract procedures and HMC case reports. Furthermore, the participants suggested that the qualities necessary for effective HMC were a wide and practical knowledge of HMC and a positive attitude. In conclusion, many patients stated that cooperation with other professionals is important in deepening pharmacists' HMC involvement, and the pharmacists hoped to establish greater communication between pharmacists and other HMC workers.
The rate of extramural prescription in Nagoya Memorial Hospital is approximately 90％ and most of our patients receive medicine in health insurance pharmacies. However, there are several problems in the prescriptions for outpatients; the patients are sometimes unable to obtain the prescribed drugs because they are out of stock in the family pharmacy. In addition, community pharmacists find it difficult to instruct individual patients when obtaining information only through externally dispensed prescriptions. To improve the cooperation between our hospital and community pharmacists, we performed a questionnaire survey on the present status of cancer patients and then another on pharmacists working in health insurance pharmacies. The first series of questionnaires showed that all patients had a family pharmacy and 92% of them agreed to give their information to it. In addition, the patients being prescribed oral cancer drugs would more often consult the community pharmacists, compared to those receiving parenteral chemotherapeutic agents. The second series of questionnaires for community pharmacists revealed that around 90% were interested in obtaining more information from their hospital, although less than one fifth of them could talk to patients undergoing cancer treatment. Based on these results, we discussed with community pharmacists and designed a communication form of cooperation. The form of cooperation was sent from the hospital to the health insurance pharmacy by FAX, after obtaining informed consent from the patients. This form is to be evaluated from the viewpoints of patients and community pharmacists and then further improved.