Drug-drug interactions

Several drugs are using to obtain a desired therapeutic objective or to treat coexisting diseases. The choice of drugs should be dependent on pharmacological characteristics. Interactions may be either pharmacokinetic or pharmacodynamic. In pharmacokinetic interaction, drugs may interact at any point during their absorption, distribution, metabolism, or excretion; the result may be an increase or decrease in the concentration of drug at the site of action. Metabolic enzyme, cytochrome P450, which metabolites any drugs is important in pharmacokinetic interaction. As characteristics change in their rates of disposition of using drug, the magnitude of an interaction that changes pharmacokinetic parameter is not always predictable but can be very significant. In pharmacodynamic interaction, drugs may interact at common receptor site or have additive or inhibitory effects due to actions at different sites in an organ. A drug interaction should be suspected danger when unexpected effects are observed. Careful drug histories are important, because patients may take over-the-counter drugs, may take drugs prescribed by another physician, or may take drugs prescribed for another patient. Care should be exercised when major changes are made in a drug regimen. Then, drugs that are not necessary should be discontinued. The major work of the medical staff of a hospital is to determine if an interaction has occurred and the magnitude of its effect. The interacting drugs should be used effectively with adjustment of dosage or other therapeutic modifications when an interaction is observed

Phorbol ester stimulates catecholamine synthesis in isolated bovine adrenal medullary cells

AbstractIn isolated bovine adrenal medullary cells, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C, stimulated [14C]catecholamine synthesis from [14C]tyrosine, but not from [14C]DOPA. This stimulatory effect of TPA on [14C]catecholamine synthesis was not dependent upon extracellular Ca2+, and TPA did not affect the uptake of 45Ca2+ or the release of catecholamine by the cells. TPA also did not affect the intracellular cyclic AMP (cAMP) level. 4α-Phorbol 12,13-didecanoate, which is not an activator of protein kinase C, did not stimulate the synthesis of [14C]catecholamine from [14C]tyrosine. The stimulatory effect of TPA on [14C]catecholamine synthesis was additive with that of carbamylcholine, but not with that of dibutyryl cAMP (DB-cAMP). From these results, it was suggested that protein kinase C is involved in the regulation of tyrosine hydroxylase activity and that this regulatory mechanism might be similar to that involving cAMP

Effect of ursodeoxycholic acid on azoxymethane-induced aberrant crypt foci formation in rat colon : in vitro potential role of intracellular Ca2+

The studies were conducted to examine the precise nature of the suppressive effect of ursodeoxycholic acid (UDCA) on colonic aberrant crypt foci (ACF) formation. Fischer 344 rats were treated with a single dose of azoxymethane (AOM) (20 mg/kg, s.c.) and fed basal diet (MF) supplemented with UDCA (0.4%) during an initiation or a post-initiation stage. ACF were enumerated at the 2nd, 5th and 8th weeks after AOM administration (15-18 rats/group).The number of ACF in the UDCA treated group was decreased significantly in the initiation and post-initiation stages at the 2nd (Plt0.01, Plt0.0001) and 8th weeks (Plt0.001, Plt0.0001),respectively, compared with untreated controls. In the time-course experiments, the effect of continuous feeding of UDCA (0.4%) on ACF formation was evaluated. ACF number was decreased significantly (Plt0.005) until the 16thweek.UDCAshowed a significant dose-dependent suppression of ACF number from a range of 0.1-0.4%UDCA.To approach the subcellular mechanisms of the effect of bile acids, the intracellular free Ca2+ concentration ([Ca2+]i) of bile acid-treated rat colonic cancer cells (ACL-15) was examined. DCA and CDCA, which are promotive on ACF formation, induced a rapid increase in [Ca2+]i, while UDCA and CA, which are suppressive or non-effective on ACF formation, did not. These findings suggest that the promotive effect of bile acids may involve intracellular Ca2+ signaling

Possible role of bradykinin on stimulus-secretion coupling in adrenal chromaffin cells

Nonapeptide bradykinin is known to be a central nervous system neurotrans-mitter and to play a role in regulation of neuronal function. However, few details are known of the function of its peptide on stimulus-secretion coupling in neuronal cells. In this article, the role of bradykinin on catecholamine biosynthesis, secretion and Ca2+movement in adrenal chromaffin cells as a model for catecholamine-containing neurons are examined. Bradykinin receptors are classified as B1 and B2 receptor subtypes. These receptors are present on the adrenal chromaffin cell membrane. Bradykinin increases the influx of Ca2+ and the turnover of phosphoinositide through the stimulation of bradykinin B2 receptor. The secretion of catecholamine from the cells is initiated by the raise of [Ca2+]i. An increase in [Ca2+]i and production of diacylglycerol stimulate the activation of calcium-dependent protein kinases. These kinases stimulate the activation of tyrosine hydroxylase, a rate-limiting enzyme in the biosynthesis of catecholamine. Otherwise, bradykinin increases Ca2+ efflux from the cells through the stimulation of the bradykinin-B2 receptor. This action may be explained by an extracellular Na+-dependent mechanism, probably through acceleration of Na+/Ca2+ exchange. It is interesting that bradykinin, which stimulates the biosynthesis and secretion of catecholamine in adrenal chromaffin cells, plays a role in the termination of calcium-signal transduction through the stimu-lation of Ca2+ efflux from the cells

EGFR Mutations in NSCLC treated with Afatinib

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as afatinib are used for non-small cell lung cancer (NSCLC) and show varying efficacy depending on EGFR gene mutation. Few studies have examined the relationship between EGFR gene mutations and the adverse events of afatinib in NSCLC. This retrospective study included 32 Japanese patients with NSCLC with EGFR gene mutation who were treated with afatinib between May 2014 and August 2018 at Kagawa University Hospital. Among the 32 Japanese patients with NSCLC treated with afatinib, 19 patients were positive for exon 19 deletion mutation (Del 19) and 13 patients were negative for Del 19. The incidence of grade ≥ 2 skin rash was slightly higher in patients positive for Del 19 (42.1% vs. 7.7%, P = 0.050). No significant differences were detected in other adverse events between the two patient groups. Patients positive for Del 19 also showed significantly longer median progression-free survival (288 vs. 84 days, P = 0.049). Our study indicates a higher incidence of skin rash associated with afatinib treatment in Japanese patients with NSCLC positive for Del 19 compared with patients without Del 19. The Del 19 positive patient group also showed better progression-free survival

Disclosure of cancer and doctor's view of pharmacist : Investigation of doctor's view in University Hospital, The University of Tokushima School of Medicine

In the present study, we investigated the consensus in the truth telling of cancer and teaching about medication by pharmacists by using a questionnaire among 24 physicians in the Third Department of Internal Medicine, the University of Tokushima School of Medicine. At the same time, the data was compared to the previous investigation in 1995. The Physicians' opinion in the truth telling of cancer have changed in these seceral years, that is summarized as positive in truth telling. In 1995, 40% of the physicians were against to tell the truth with pharmacists, but in the present study, most physicians wanted to tell the truth with pharmacists. As for the teaching about medication by pharmacists, most physicians supported pharmacists to teach about medication, even to the patients who do not know the truth about their own cancer. These results suggest that it is necessary for the pharmacists to positively relate to the cacer patients through the truth telling and the teaching about medication

Effect of evodiamine on catecholamine secretion from bovine adrenal medulla

The effect of evodiamine on catecholamine secretion from bovine adrenal medulla was investigated. Evodiamine, a bioactive component isolated from dry unripened fruit of Evodia rutaecarpa Bentham, was found to stimulate the secretion of catecholamine from perfused bovine adrenal medulla at a concentration of 10 μM and its effect persisted for at least 30 min. This stimulatory effect of evodiamine was abolished by omission of Ca2+ from the perfusion fluid. Evodiamine (0.1-10 μM) markedly enhanced the secretion of catecholamine from the adrenal medulla induced by acetylcholine (100 μM) or high K+(56 mM). The secretion of catecholamine was promptly enhanced by acetylcholine or high K+, but returned to the control level on treatment for 20 min. However, when evodiamine was added to the perfusion fluid after acetylcholine or high K+ stimulation for 10 min, the secretion of catecholamine again increased greatly. These results indicate that evodiamine not only stimulated the secretion of catecholamine from bovine adrenal medulla but also reversed insensitivity of these cells to acetylcholine or high K+ stimulation

INTRODUCTION Clinical trials leading to drug approval (registra- tion trials) play a central role in the drug devel- opment process, and clinical trials in the general View and present status of personnel involved in clinical trials : a survey of particip

. Among the support staff, 36 (80% %) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was "willing to contact staff from other medical institutions or organizations" for support staff and "to obtain further knowledge concerning clinical trials" for medical staff. The overall view of the discussion ("Was the discussion satisfactory?") was favorable for 36 (53% %) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further development of the clinical trial infrastructure, including training opportunities and career development for support staff, is required. Due to the limitations of this study, further analysis is warranted to determine the optimal strategy for training support staff. J. Med. Invest. 58 : 81-85, February, 201

View and present status of personnel involved in clinical trials : a survey of participants from the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials

Clinical trials leading to drug approval (registration trials) play a central role in the drug development process. Since the introduction of the Good Clinical Practice (GCP) standard in 1997, the Japanese infrastructure for registration trials has improved. The contribution of support staff, including clinical research coordinators (CRCs), to clinical trials is now widely recognized in Japan. Quality issues and career development for these support staff are being increasingly emphasized. The Shikoku Collaborative Group for Promotion of Clinical Trials was organized in 2008 to address these issues through communication with the personnel involved in clinical trials in regional areas of Japan. To understand the views and present status of personnel involved in clinical trials, we used questionnaires to survey the participants of the First Symposium of the Shikoku Collaborative Group for Promotion of Clinical Trials held in August 2009. Group discussions and special lectures occurred at the symposium. The questionnaire began with questions about basic patient characteristics, followed by practical questions. Of 110 participants, there were 68 respondents (62%), including clinical trial support staff (clinical research coordinators [n=36, 53%], administrative officers [n=9, 13%]), and medical staff [n=23, 34%]). Among the support staff, 36 (80%) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was “willing to contact staff from other medical institutions or organizations” for support staff and “to obtain further knowledge concerning clinical trials” for medical staff. The overall view of the discussion (“Was the discussion satisfactory?”) was favorable for 36 (53%) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further development of the clinical trial infrastructure, including training opportunities and career development for support staff, is required. Due to the limitations of this study, further analysis is warranted to determine the optimal strategy for training support staff

イデン ソウダンシツ ト イデン カウンセリング

Genetic research has advanced rapidly which has enabled us to identify diseases in their early stages, making it easier to accurately predict the prognosis. On the other hand, public alarm is increasing with regard to ethical, legal and social issues. To alleviate and improve this situation, it is necessary to ensure that medical professionals have the relevant training and expertise in order to allay any public fears. For these reasons, the genetic counselling room was opened at Tokushima University Hospital. A Doctor and a Nurse are available for counselling every Monday, Tuesday, Thursday, and Friday. To date they have dealt with 50 cases which were based on various reasons and they encountered no major problems. To deliberate any matters in various aspects and prevent trouble, we make it a rule to decide anything by staff conference. To level up staff, we have performed study sessions. Furthermore, to raise our public profile, we have opened a homepage on the web and issued a brochure. With the expectation that genetic research will certainly advance and subsequently the necessity for counselling will also increase, it is necessary to continue developing our counselling system