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

The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease : a randomized placebo-controlled clinical trial

The progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day). We recruited patients with CKD stage 2 and 3 whose plasma aldosterone concentration was above 15 ng/dL based on the prior data of a prospective observational study. In the CKD cohort study (n = 141), baseline plasma aldosterone concentration was identified as an independent contributory factor for the future rate of change in estimated glomerular filtration rate (eGFR). When the cut-off value for aldosterone was set at 14.5 ng/dL, the decline rate was significantly higher in patients with higher plasma aldosterone concentration (− 1.22 ± 0.39 ml/min/1.73 m2/year vs. 0.39 ± 0.40 ml/min/1.73 m2/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone

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

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

Home-based aerobic exercise and resistance training

Background The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home-based exercise programme on physical functioning and health-related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15–30 mL/min/1.73 m2. Methods Forty-six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40–60% peak heart rate thrice weekly and resistance training at 70% of one-repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life—Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD. Results Improvement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. −21.3 ± 46.1; P < 0.001). Among Kidney Disease Quality of Life domains, significant mean differences were observed between the exercise group and the control group in work status, quality of social interaction, and kidney disease component summary outcomes (12.76 ± 5.76, P = 0.03; 5.97 ± 2.59, P = 0.03; and 4.81 ± 1.71, P = 0.007, respectively). There were greater reductions in natural log (ln)-transformed urinary excretion of liver-type fatty acid-binding protein, ln serum C-reactive protein, and acylcarnitine to free carnitine ratio in the exercise group compared with controls, with significant between-group differences of −0.579 ± 0.217 (P = 0.008), −1.13 ± 0.35 (P = 0.003), and −0. 058 ± 0.024 (P = 0.01), respectively. Conclusions Our 6 month home-based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD-related parameters

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