Making digoxin therapeutic drug monitoring more effective

Digoxin is an important drug in the treatment of patients with either congestive heart failure or atrial arrhythmia. Because of its narrow therapeutic range, digoxin serum concentrations are commonly monitored in both inpatients and outpatients. However, with the costs of health care skyrocketing, there is debate whether such therapeutic drug monitoring (TDM) is cost-effective. To reduce the number of samples drawn too soon after a previous dose and in an effort to improve digoxin TDM at this teaching hospital, a new dosing and monitoring policy was initiated. This policy involved uniform digoxin dosing at 5 p.m. (1700 h) for all inpatients and serum drug measurements at 7 a.m. (0700 h) the next day. By coordinating the time of dosing to be greater than 12 h prior to serum digoxin analysis, the number of inappropriate digoxin serum determinations have been reduced. This new protocol has increased the effectiveness of the toxicology laboratory and enhanced the efficiency of the house staff. Other issues concerning digoxin TDM are also addressed. These findings can be generalized to all drugs that are monitored at any hospital and can result in a significant cost savings and decrease the time spent analyzing inappropriate data.     

Towards safer and more predictable drug treatment--reflections from studies of the First BCPT Prize awardee

This MiniReview is a personal recollection of selected research topics, which the author in collaboration with colleagues has studied, aiming to improve the predictability of drug therapy. In early studies, we found bi- and trivalent cations to reduce the absorption of various tetracyclines and fluoroquinolones. Certain antacids elevated the bioavailability of some non-steroidal anti-inflammatory drugs and sulphonylureas. Various brands of phenytoin tablets revealed great differences in their bioavailability, causing clinical consequences. Numerous factors affecting the antidotal effect of activated charcoal were also studied, with charcoal compared to other gastrointestinal decontamination methods, including ipecac and gastric lavage. Effect of age and diseases on the pharmacokinetics of drugs was a research topic. Acute sotalol intoxications revealed its QT-prolonging properties, and even small mixed overdoses of moclobemide with serotonergic drugs proved fatal. Itraconazole and other potent inhibitors of CYP3A4 could drastically increase exposure to drugs like midazolam, triazolam, buspirone, lovastatin, simvastatin and oxycodone, whereas rifampicin greatly reduced their plasma concentrations. A change from potent inhibition to induction caused a 400-fold change in the exposure to oral midazolam. CYP2C8 was revealed to be crucial in the metabolism and interactions of several drugs. Many interactions affecting statins are CYP3A4-mediated, but transporters are important in certain interactions. Tizanidine is very susceptible to CYP1A2 inhibition. Fruit juices such as grapefruit juice can raise or lower exposure to different drugs. Both drug interactions and pharmacogenetics can modify the activity of cell membrane transporters and cause variability in the pharmacokinetics of and response to their substrate drugs.     

Applying pharmacogenomics to enhance the use of biomarkers for drug effect and drug safety

Pharmacogenomics is used to improve patient outcome by maximizing the likelihood of desired effects and minimizing the risk of adverse events using an individual's genetic profile. As such, pharmacogenomics can be used to improve current risk-management strategies (improving the risk-benefit balance). Two areas of great promise for pharmacogenomics in this regard are emerging: (i) the pharmacogenomics of modulating disease biomarkers (to provide insight into novel mechanisms of drug response and to identify the patients most likely to respond to a drug in a favorable way); and (ii) using pharmacogenomics to enhance drug safety. Given that novel biomarkers could enable the earlier detection of many diseases and more-widespread therapies for primary prevention, pharmacogenomics provides the opportunity to identify the patients most likely to respond to these therapies, thereby preserving valuable health-care resources. The use of pharmacogenomics in pharmacovigilance could also be useful for risk-stratifying patients and for helping to identify the mechanisms involved in adverse events.     

Lactoferrin delivery systems: approaches for its more effective use

INTRODUCTION: Recently, pharmacotherapy has advanced extensively, but there are still many refractory diseases which cannot be solved fully by existing therapeutic agents. Therefore, alternative medicine and health foods are now attracting much attention, for example, lactoferrin (LF): a multifunctional glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and therapeutics is expected to be widespread. AREAS COVERED: In this review, LF's general basic features are described. The interaction of LF with its receptors activates the immune system, including cytokine production and balance. In particular, the immune activation of orally administered LF is considered as a new strategy for the treatment of refractory diseases, such as inflammatory bowel disease, virus infection and tumor metastasis. Also mentioned are the problems associated with the use of LF. As LF is degraded rapidly in the body due to enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate delivery system may improve these problems and increase its efficiency. EXPERT OPINION: Chemical modifications, such as PEGylation, can enhance the stability of LF in the body, resulting in increased efficacy. Also, liposomes and enteric or microparticulate formulations can promote the function of LF in oral administration due to target site delivery and protection of LF from enzymatic hydrolysis. These delivery systems are expected to improve the utility of LF.     

Lactoferrin delivery systems: approaches for its more effective use

Introduction: Recently, pharmacotherapy has advanced extensively, but there are still many refractory diseases which cannot be solved fully by existing therapeutic agents. Therefore, alternative medicine and health foods are now attracting much attention, for example, lactoferrin (LF): a multifunctional glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and therapeutics is expected to be widespread.

Areas covered: In this review, LF's general basic features are described. The interaction of LF with its receptors activates the immune system, including cytokine production and balance. In particular, the immune activation of orally administered LF is considered as a new strategy for the treatment of refractory diseases, such as inflammatory bowel disease, virus infection and tumor metastasis. Also mentioned are the problems associated with the use of LF. As LF is degraded rapidly in the body due to enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate delivery system may improve these problems and increase its efficiency.

Expert opinion: Chemical modifications, such as PEGylation, can enhance the stability of LF in the body, resulting in increased efficacy. Also, liposomes and enteric or microparticulate formulations can promote the function of LF in oral administration due to target site delivery and protection of LF from enzymatic hydrolysis. These delivery systems are expected to improve the utility of LF.     

Injection drug use cessation and use of North America's first medically supervised safer injecting facility

BackgroundVancouver, Canada has a pilot supervised injecting facility (SIF), where individuals can inject pre-obtained drugs under the supervision of medical staff. There has been concern that the program may facilitate ongoing drug use and delay entry into addiction treatment.MethodsWe used Cox regression to examine factors associated with the time to the cessation of injecting, for a minimum of 6 months, among a random sample of individuals recruited from within the Vancouver SIF. In further analyses, we evaluated the time to enrolment in addiction treatment.ResultsBetween December 2003 and June 2006, 1090 participants were recruited. In Cox regression, factors independently associated with drug use cessation included use of methadone maintenance therapy (Adjusted Hazard Ratio [AHR] = 1.57 [95% Confidence Interval [CI]: 1.02–2.40]) and other addiction treatment (AHR = 1.85 [95% CI: 1.06–3.24]). In subsequent analyses, factors independently associated with the initiation of addiction treatment included: regular SIF use at baseline (AHR = 1.33 [95% CI: 1.04–1.72]); having contact with the addiction counselor within the SIF (AHR = 1.54 [95% CI: 1.13–2.08]); and Aboriginal ancestry (AHR = 0.66 [95% CI: 0.47–0.92]).ConclusionsWhile the role of addiction treatment in promoting injection cessation has been well described, these data indicate a potential role of SIF in promoting increased uptake of addiction treatment and subsequent injection cessation. The finding that Aboriginal persons were less likely to enroll in addiction treatment is consistent with prior reports and demonstrates the need for novel and culturally appropriate drug treatment approaches for this population.     

Quality measures of antimicrobial drug use

Antimicrobial use is the major determinant in the development of resistance. Many parameters of importance for optimal quality of antimicrobial therapy have already been defined. Maximal efficacy of the treatment should be combined with minimal toxicity at the lowest cost. Quality of antimicrobial drug use is dependent on knowledge of many aspects of infectious diseases. Considering efficacy, many of our indications for antimicrobial use need critical evaluation. Irrational use should be discouraged. Avoidance of the development of resistance is a quality parameter that will need increasing attention. This paper reviews the well-established factors that may influence the appropriateness of pharmacotherapy with antimicrobial drugs. It cites recent evidence supporting principles of prudent prescribing and gives an overview of audits that have addressed these parameters. Measures relating to resistance are discussed.     

A perspective on more effective GPCR-targeted drug discovery efforts

Background: G-protein-coupled receptors (GPCRs) form the largest receptor family in mammalian genomes and over the years they have repeatedly proven themselves to be druggable targets. The activation of a GPCR (usually by ligand binding) results in conformational changes that lead to G-protein coupling with subsequent activation of downstream effectors and ultimately a cellular response. GPCRs can be modulated at several strategic signaling positions including ligand binding, G-protein coupling, phosphorylation, internalization, and recycling. Objective: As the complexities of GPCR activation and signaling become more recognized, new technologies have been sought for the identification of ligands that can alter not only receptor activation but also receptor action. Methods: Taking into consideration the key contact sites, this review will cover several points to bear in mind both when developing a screening campaign for a GPCR and when validating the hits obtained from those primary screens. Results/conclusions: The final selection of which screen to use for a given GPCR should take into account the end goal of the drug, such as inflammation, and work towards utilizing screens that allow physiological end points in this case chemotaxis, relevant cell types, and endogenous receptors whenever possible.     

Injection drug users' perceptions regarding use of a medically supervised safer injecting facility

BACKGROUND: In recent years, there has been increased interest in supervised safer injecting facilities (SIF) as a strategy to reduce the harms of illicit drug use; however, little work has been done to assess drug users' satisfaction with this service. This study was undertaken to explore injection drug users' experiences and opinions regarding North America's first SIF in Vancouver, Canada. METHODS: Injection drug users (IDU) were randomly recruited from within the Vancouver SIF and invited to enroll in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort. For the present study, participants were then surveyed regarding their experiences and beliefs regarding the SIF. RESULTS: Of 1082 IDU surveyed, 809 (75%) reported that their injecting behavior had changed as a result of using the SIF. Among these individuals, 80% indicated that the SIF had resulted in less rushed injecting, 71% indicated that the SIF had led to less outdoor injecting and 56% reported less unsafe syringe disposal. The three most common features always or usually limiting IDU's use of the SIF were: travel to the SIF (12%), limited operating hours (7%), and waiting times to access the SIF (5%). When asked in what ways the SIF might be improved, the three most common suggestions were: longer hours of operation (53%), addition of a washroom (51%), and reduced waiting times (46%). CONCLUSIONS: Many IDU reported changes in their injecting behaviors that have important implications for community and public health. Addressing a number of programmatic issues related to operating hours and waiting times, and the provision of additional amenities within SIF, may help to further improve their impact.     

门诊处方不合理用药调查结果分析及措施

目的：探讨医院门诊处方不合理用药的调查情况,并研究具体的措施加以干预。方法：我院临床药学组将我院2013年7月～2015年12月共28个月每月随机抽取的门诊处方150张共4200张作为本次研究对象。按处方点评根据药物选择不合理、用药方式选择不恰当、药物配伍以及联用不合理、药物未合理使用、出现滥用药物的情况以及药物使用剂量不当等展开统计分析。结果：经过统计分析发现,在所有应用处方中,不合理用药处方共包括136张,占3.23%;其中药物滥用21例,用药剂量不正确14例,配伍以及联用药物不合理50例,药物使用方法不合理15例,用药方式选择不当11例,选择药物不合理16例,药物应用时间不正确13例。结论：我院门诊处方还存在不合理用药情况,建议医务科、质控科、临床药学室要针对不合理用药情况进行分析,选择有效方法针对性干预,提高临床用药的合理性,对患者的利益进行有效保护。     

Program use of effective drug abuse treatment practices for juvenile offenders

This study examined the extent to which organizational context predicted use of consensus-based elements of effective substance abuse treatment practices with juvenile offenders. Participants were either directors of substance abuse treatment programs located in residential facilities (institutional sample) or directors of community-based treatment agencies providing services to adolescents in their home communities (community sample). The two settings differed significantly in the number and types of effective practices they were using. Community programs were more likely to have staff qualified to deliver substance abuse treatment, involve families in treatment, and assess their treatment outcomes. In contrast, institutional programs were more likely to provide comprehensive services. Resources dedicated to training, internal support for new programming, and network connectedness with non-criminal-justice facilities were associated with greater use of effective practices. These findings highlight the importance of establishing corrections-community partnerships designed to promote continuity of care for juvenile offenders.