Pharmacists have a professional obligation in medicine. As a member of a medical team to provide a safe medication, it is important that they be involved with drug safety in mind. Currently a pharmacist in a business operating with a focus on traditional dispensing and drug administration also functions with a focus on patient care and the provision of drug information. It is important that a pharmacist has a risk management approach to medicine. Together with the institutions responsible for drug safety, he must be cognizant of published reports to prevent serious adverse drug reactions as well as taking part in post-marketing surveillance. Management of safety information for high-risk pharmaceutical drugs, also falls to the pharmacist. Thus he must have knowledge of the skill required for the job of each member of the health care team. Recent newly added responsibilities are: advice in planning patient treatment, checking vital signs and the prescription brought to him to fill. In short a pharmacist working in the medical field must, above all, respect and assure safety to the patients he serves.
One of the important roles of pharmacists is to continue their contributions to new drug discovery and development. However, it seems to be very difficult to obtain patient satisfaction with new drugs. Because new medicines have both benefit and risk, there should be many systems to maximize the safety and efficacy of the drugs. In clinical trials, the rights, safety and welfare of human subjects under the investigator's care must be protected. Good Clinical Practice is a harmonized ICH-guideline, and the safety information of an investigational product is explained to patients who voluntarily enter the clinical trials. Since safety information about investigational products is still limited, subjects are informed about the results of animal experiments and those of finished clinical trials. The sponsor of clinical trials should be responsible for the on-going safety evaluation of the investigational products. When additional safety information is collected in the clinical trials, the written informed consent form should be appropriately revised. During the review process, quality, safety and efficacy of new drugs are evaluated and judged based on the scientific risk-benefit balance. The safety information collected in clinical trials is reflected in the decision-making process written in the review reports. All-case investigation should be also performed until data from a certain number of patients has been accumulated in order to collect early safety and efficacy data. Important messages written in review reports for drug safety and patient consent are explained. Risk communication will improve the application of patients' consent for new drugs.
We need the surroundings in which we can conduct sciences-based safety measurements and continue to do scientific approach in order to ensure the safety of drugs and put patients and the nation at ease. It is important that we actively conduct clinical trials to evaluate the efficacy and safety of drugs, and supply the results to medical scene quickly. Japanese government draws up some plans to activate clinical trials, and intends to improve national health and promote ability of research and development of drugs. Since activation of clinical trials is important for progression of medicine too, drug companies are also expected to take part in it positively.
Patients expect drugs are 100% effective and safe. Unfortunately, however, most drugs are not. Continuous efforts by healthcare professionals and industry should be made to maximize efficacy and safety. Here, four challenges are shown from a viewpoint of laypersons. 1) Develop better drugs: Continuous efforts to develop drugs for ‘neglected’ diseases should be enhanced to meet unmet medical needs. 2) Deliver right drugs: Medication errors caused by similar names and shapes have been repeatedly reported. Communication with patients and their families may be helpful to decrease errors. 3) Improve the quality of drug information: How health professionals provide drug information to patients should be routinely monitored to improve the quality. Rephrasing to plain expressions may sometimes be useful for better communication. 4) Promote personalized medicine: Each patient wants to know whether this drug would work to him/herself as well as statistical data. Pharmacogenomics and pharmacokinetics/pharmacodynamics (PK/PD) research should be encouraged in order to develop personalized medicine.
In contrast with the 20th century's dramatic improvements in the direct and/or hazardous toxicity of drugs, indirect toxicity and/or long-term safety concerns such as relation of cancer risk and TNF-alpha receptor blockers have caused significant complexity in post-marketing surveillance (PMS) scenery. The post-marketing phase of drugs and their safety measures now appear to be much more complicated and heavier than decades ago. The spontaneous adverse drug reaction (ADR) reporting system which has been one of the main pillars of PMS measures for almost 50 years may have to be reviewed in terms of its effectiveness, and may need augmentation from medical data bases. Only a pharmaco-epidemiological analysis and integration of the output with a conventional spontaneous reporting approach offers a chance to satisfy the current complex safety issues. Today's tendency toward practical saturation at medical/pharmaceutical frontiers, by regulatory authorities and safety divisions of pharmaceutical companies with ever-increasing day-to-day safety information can also be pointed out. Such phenomena may actually reduce the productivity of safety measures and also jeopardize the maintenance of an acceptable risk/benefit drug ratio. To alleviate these potential negative implications, establishment of a consortium to act as a sentinel that would gather up-to-date and essential safety information, including epidemiological data, from all sources and provide it plus recommendations to all stakeholders can be suggested. Through such activities, we could expect significant improvement of drug safety measures in post-marketing phase which would effectively cover not only new drugs but also generic and bio-simulated drugs.
A six-year program started in 2006, and Computer Based Testing (CBT), Objective Structured Clinical Examination (OSCE) and long-term practical training were introduced into the pharmacy education. As a member of the team medical care, we participate in medical care positively, and a pharmacist now wanted is who could be able to communication well with the medical worker and the patient has. We have the results of 32 years as a cramming school for the pharmacist national examination candidate. We have life study center, a hospital, a pharmacy, and the publishing division. Firstly we taking part in the education, learn the present conditions, the clinical cases, and stream down it to a student, and it is necessary to send it in the future of a pharmacy and the pharmacist. Therefore we carry out studying society of the prescription, an experience of the compounding of medicines training, participation to the life study. At this symposium, we give a lecture on diabetes based on the situation of pharmacy education, the clinical spot, medical supplies development. We introduce condition of a patient physiology of the diabetes, the difference of the model, a symptom, inspection, efficacy of the medicine, a side effect in that. Thus, we want to propose some technical skills for relating these clinical conditions in the future education.
In Japan, the number of diabetic patients has increased steadily. According to a 2007 report by the Ministry of Health, Labour and Welfare, the number of diabetic patients and its reserves is estimated to be 22 million, or a fifth of adults. On a global scale, the number of deaths due to diabetes is almost equivalent to that due to AIDS. Therefore, in 2006, WHO designated November 14 as World Diabetes Day and began a worldwide campaign to increase people's awareness of diabetes. Diabetic patients usually fluctuate between good and bad data of SMBG (self-monitoring of blood glucose). However, the main goal of diabetes treatment is to not only keep good data of SMBG but also prevent diabetes-related complications from arising, because such complications have a major impact on patients' QOL and medical costs. At medical institutions, CDEJs (Certified Diabetes Educator of Japan, a qualification awarded to health care professionals such as nurses, dietitians, pharmacists, laboratory technicians, and physiotherapists) provide information to diabetic patients in order to increase their knowledge of the disease; such professionals also assist with patients' medical treatments. I would like to discuss frequently used diabetes medications, the latest treatments for diabetes, the problems faced by diabetic patients, and so on, from the perspective of a hospital pharmacist.
Many foods are known to have not only nutritive and taste values but also medicinal effects. In Chinese traditional medicine, the treatment using medicinal foods has been recommended highly. Recently, we examined the effects of the extract and constituents of several medicinal foods on experimental models of diabetes. In this paper, we focus on the bioactive constituents of four medicinal foods, namely the antidiabetic constituents from 1) the roots, stems and leaves of Salacia plants, 2) the male flowers of Borassus flabellifer, 3) the flower buds of Camellia sinensis, 4) the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium).
It might be seen as reckless to challenge to create single-agents for the treatment of both type 1 diabetes caused by the destruction of the Langerhans β cells in pancreas by excessive autoimmunity, and type 2 diabetes caused by the obesity. However, we hypothesized that retinoid X receptor (RXR) agonists, which are researched for the treatment of type 2 diabetes, will also be useful like metformin, which shows insulin-sparing effect in type 1 diabetes. This is because PPARγ/RXR is known to be a target of thiazolidinediones (TZDs), which are used for the treatment of insulin resistance, LXR/RXR is reported to be involved in glucose/lipid metabolism, and these heterodimers can be activated by RXR agonists alone (permissive mechanism). However, repeated administration of RXR agonists can elevate blood triglyceride and induce hypothyroidism. In this study, we performed systematic conversion of the alkoxy side chain of 5a (6-[ethyl-(3-isopropoxy-4-isopropylphenyl)amino] nicotinic acid: NEt-3IP) and evaluated the RXR-, PPAR/RXR- and LXR/RXR-agonist activities of the products. The cyclopropylmethoxy analog (5c) showed similar RXR- and LXR/RXR-agonistic activities to the benzyloxy analog (5i) and n-propoxy analog (5k), but exhibited more potent PPAR/RXR-agonistic activity than 5i or 5k. Differential modulation of RXR heterodimer-activating ability by conversion of the alkoxy group located in the lipophilic domain of the RXR-agonist common structure is expected to be a useful approach in the design of new RXR agonists for the treatment of hyperlipidemia.
In recent years, people all over the world have suffered from various diseases such as cancer, myocardial infarction, osteoporosis, hypertension, and diabetes mellitus (DM). Especially, DM, well-known as one of lifestyle-related diseases, has been regarded as a serious problem, because it is difficult to fully recover. The number of patients suffering from DM in 2007 was reported to be approximately 200 million people worldwide. However, insulin preparations and synthetic therapeutics, which are clinically used treatment of DM, have been associated with problems such as physical and mental pain due to daily injections and certain severe side effects, respectively. Zn, which is an essential trace element in animals and humans and plays an important role in maintenance of their lives, has been indicated to exhibit insulin-like activity. Since the finding of insulin-like effects of Zn, several Zn complexes have been proposed as a new type of anti-diabetic therapeutics which is differ from existing medicines. In this symposium, we introduce the anti-diabetic effect, complication relieving effect, and action mechanism of bis(2-mercaptopyridine-N-oxidato)Zn complex with Zn(S2O2) coordination mode.
We would like to introduce our new project to develop a course program for the 4-year system of graduate school of pharmacy Tohoku University after the 6-year program of the college of pharmacy. New course program designed will be two fields of ‘cancer chemotherapy’ and ‘life-style related diseases’ for clinical specialists and scientists of pharmacy. Our vision through this new program is to educate and produce the preeminent personnel being responsible for the safety and effective pharmaceutical care service in the clinical settings, with having the practical professional knowledge, skill and highly research ability, such as doing intervention and recommendation against a prescription planning process with an appropriate drug use. The personnel educated using our program will be called ‘a next generation type pharmacist (or a Japanese-style pharmacist practitioner)’. Our program is a joint project with the graduate school of medicine and the university hospital, Tohoku University. The College of Pharmacy, Tohoku University placed two new laboratories and employed six faculties who are registered pharmacists in order to achieve above, and they also hold the post of pharmacist of the university hospital. And graduate students who are registered pharmacists also work in the university hospital now.
For the purpose of the development of new drugs for incurable diseases, many students enter graduate school of pharmaceutical sciences every year. At first, I expect education to let it develop more and spread without forgetting this will. Recently, withdrawals from Japan of the research institutes of the foreign-affiliated pharmaceutical companies have occurred successively. It is pointed out that there is it for the study about the biomedical research that is the next step of fundamental researches having been weak. I expect the immediate construction of the cluster, which consists of pharmaceutical companies and graduate schools of pharmaceutical sciences. Time of ten several years and a cost of one hundred billion yen are necessary for the research and development of new drug. The success probability is low, besides. Many trials are accomplished to raise the success probability. The one is introduction of the project system. The best members are gathered from the fields such as medicinal chemistry, molecular biology, biochemistry, pharmacology, pharmacokinetics, pharmaceutics and toxicological sciences, etc. The project system is a system enforcing go or stop by own judgment, an authority and the responsibility of the purpose are given. It is necessary for the project leader to have great knowledge and the abilities to hold lively discussion. It is a researcher from graduate school of pharmaceutical sciences that is the most suited to be as a project leader. I expect to upbring education from the time when a leader is young.
The report of the Council for the improvement in the education of pharmaceutical sciences and the recommendation of the Central Council for Education indicate that the 6-year education is required to develop pharmacists with high qualities as medical staff. Each college of pharmacy started the education and practical training based on the model core-curriculum with the original program. On the other hand, to develop a scientist for the development of novel medicines, 4-year education program is also required. Under these new education systems, what we should do in the education in the graduate school of pharmacy and pharmaceutical sciences has been discussed. Recently, the first report about the purpose and the strategy in the graduate school in the new generation was submitted. Here, I will comment on the details of this report.
No true immunocytochemistry (ICC) for drugs nor its application to pharmacokinetic studies is available. Recently, our studies have shown that ICC for drugs is extremely useful for such studies by utilizing easy and safe techniques, and gives direct evidence of drug localization. We have therefore developed antibodies and a series of pretreatment conditions for the immunodetection of drugs and have localized sites of drug uptake or accumulation in several tissues of rats following the administration of drugs. This review describes preparation of anti-drug antibody, specificity of antibody, fixation of drug in situ in rat tissues and cells, treatment of paraffin section specimens prior to immunoreaction, precision, and their application to a variety of types of antibiotics anti-cancer anthracyclines daunorubicin, doxorubicin, and epirubicin, bleomycin analog peplomycin, antimicrobial agents gentamicin, and amoxicillin. ICC for the anti-cancer anthracyclines demonstrated that the drug accumulates in a characteristic pattern in the heart, liver, kidney, gastrointestinal tract, and hair follicles, which represent the sites targeted by the drug toxicity. Some, but not all, of these drug accumulations are associated with the induction of apoptosis. It was also noted that there are striking differences in accumulation among the anthracyclines in rat tissues, maybe contributing the mechanisms of the differences in anti-tumor activities of the anthracyclines. Both ICCs for gentamicin and peplomycin identified characteristic necrotic-like cells in the specific sites of the kidney, suggesting the sites are readily affected by some chemotherapeutic agents. ICC for amoxicillin demonstrated that the sites of the drug accumulation in small intestine, liver and kidney are closely correlated with the specific sites in which certain transporter systems for penicillin occur. Thus, an ICC method is a potential new tool for pharmacokinetic studies of wide variety types of drugs containing a primary amino group(s) in their molecules.
3-O-p-Coumaroyl-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-O-β-D-gulcopyranosylpropanol (ESQ10) is a naturally occurring phenylpropanoid derivative isolated from Sasa quelpaertensis (Gramineae). In the present study, we discovered that ESQ10 inhibits nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. ESQ10 attenuated LPS-induced synthesis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in parallel and inhibited LPS-induced interleukin-6 production, as determined by an enzyme-linked immunosorbent assay in the macrophages. The mechanism of the antiinflammatory action of ESQ10, i.e., suppression of nuclear factor (NF)-κB and mitogen-activated protein kinase activation, has been documented. However, ESQ10 could not influence LPS-mediated IκB-α degradation and extracellular signal-regulated kinase/c-Jun amino-terminal kinase phosphorylation at concentrations of up to 373 μM. To test the potential application of ESQ10 as a topical material, we also conducted a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human HaCaT keratinocytes as well as human dermal fibroblast cells. In this assay, ESQ10 did not induce cytotoxicity. Taken together, the results suggest that ESQ10 may be considered an antiinflammatory candidate for treating inflammatory and skin diseases.
This survey was conducted to investigate the current status and suggest future directions for clinical trials pharmacy in Korea. A 32-item survey was distributed to 96 hospital pharmacies conducting clinical trials. The questionnaire was designed to elicit information on the following: (1) general clinical trial status of each hospital, (2) Investigational Drug Service (IDS) performance status. The response rate was 59.4% and 61.8% of the respondents carried out all the regulatory IDSs. Independent of the IDS's performance, the respondent started to feel the need for reinforcement in human resources when the number of active studies crossed 35. Analyzing the workload based on the subjective need for reinforcement in CTP, the overall CTP work execution rate was significantly higher in the ‘needs reinforcement’ group (p<0.05), even though this group had a 2.3 times higher workload than that in the ‘current number of CTPs is adequate’ group. The ‘needs reinforcement’ group performed more efficiently with a better understanding of IDSs, even though the group was having difficulties due to the shortage of CTPs. The lower execution rate in the ‘current number of CTPs is adequate’ group can be assumed to be due to the lack of understanding of the scope of IDSs. The work of CTPs should evolve into one of the specialized hospital pharmacists’ roles, and a trial institution should designate at least one CTP per 40 protocols. Furthermore, the education for CTPs should be diversified into basic course and advanced course based on the IDS's performance of each hospital.
A simple, rapid and efficient extraction procedure, partitioned dispersive liquid-liquid microextraction, has been developed in combination with near-infrared spectroscopy for the extraction and discrimination of dimethoate from aqueous samples. For this technique, the appropriate mixture of extraction solvent (CCl4) and disperser solvent (THF) was utilized. Partial least squares discriminant analysis was applied to build the model with several pre-process methods over the wavenumber regions between 7100 cm−1 to 7300 cm−1. The best model gave satisfactory classification accuracy, 98.6% for calibration set (n=74) and 97.6% for prediction set (n=42), using preprocessing of standard normal variate followed by Savitzky-Golay first derivative. The method was successfully applied to bottled water, tap water, lake water and farm water samples. The results demonstrated the possibility of near-infrared spectroscopy after partitioned dispersive liquid-liquid microextraction for the identification of water contaminated by dimethoate.
The combination of anti-glaucoma eye drops is frequently used in clinical treatment, and it is known that the combination can cause corneal damage. Recently, an anti-glaucoma combination eye drops is developed, and the treatment by the combination eye drops is expected to enhance quality of life. However, effects of the combination eye drops on corneal epithelial cell damage have not been clarified. In this study, we investigated the corneal epithelial cell damage of commercially available anti-glaucoma combination eye drops, such as Xalacom® (latanoprost/timolol maleate combination eye drops), Duotrav® (travoprost/timolol maleate combination eye drops) and Cosopt® (dorzolamide hydrochloride/timolol maleate combination eye drops) using the human corneal epithelial cell (HCE-T). The cytotoxicity in Xalacom® was higher than that in Xalatan® (eye drops containing latanoprost) and Timoptol® (eye drops containing timolol maleate), and the benzalkonium chloride (BAC) and timolol maleate were related to cytotoxicity in Xalacom®. The cytotoxicity in Duotrav® and Cosopt® was lower than that in Timoptol®. The Duotrav® is preserved with a non-BAC system (POLYQUAD, polidronium chloride). Therefore, it was suggested that the POLYQUAD related to the low cytotoxicity in Duotrav®. On the other hand, the D-mannitol reduced the cytotoxicity by BAC in this study. This result suggested that the cytotoxicity in Cosopt® was reduced by D-mannitol. The Duotrav® and Cosopt® may be less damaging to the ocular surface of glaucoma patients receiving long-term eye drop therapy in compared with the combination of anti-glaucoma eye drops.
Panaxydol (PND) is one of the main non-peptidyl small molecules isolated from the lipophilic fractions of Panax notoginseng. The present study was carried out to demonstrate the potential effects of panaxydol on the induction of differentiation of human liver carcinoma cell lines SMMC-7721. Cell viability was evaluated by MTT method and Trypan blue exclusion assay respectively. The changes of morphology were detected by transmission electron microscope. Inhibitors were applied to detect the signaling pathway of differentiation. The level of intracellular cyclic AMP was determined by radioimmunoassay. The expression of p-ERK, Id1, and p21 were determined by Western blot. We found that panaxydol inhibit the proliferation of SMMC-7721 cells and caused the morphology and ultrastructure changes of SMMC-7721. Moreover, panaxydol dose-dependently increased the secretion of albumin and alkaline phosphatase activity, and decreased the secretion of AFP correspondingly. These changes of differentiation markers in SMMC-7721 can be reversed by the protein kinase A inhibitor RpcAMPS and by MAP kinase kinase 1/2 inhibitor U0126 or sorafenib. Intracellular cAMP was elevated by panaxydol in SMMC-7721 cells. Panaxydol dose-dependently decreased the expression of regulatory factors Id1 and increased the protein levels of p21 and p-ERK1/2 correspondingly. It suggested panaxydol might be of value for further exploration as a potential anti-cancer agent via cAMP and MAP kinase-dependent mechanism.