Johan J. de Gier

Drugs and driving

The authors present a global overview on the issue of drugs and driving covering four major areas: (1) Epidemiology and Prevalence—which reviews epidemiological research, summarizes available information, discusses the methodological shortcomings of extant studies, and makes recommendations for future research to better define prevalence and epidemiology; (2) Effects of Medicinal and Illegal Drugs on Driving Performance—focuses on the six classes of drugs most often found in impaired and injured drivers, draws conclusions regarding the risk of these drugs to traffic safety and discusses the need for additional research; (3) Toxicological Issues—discusses ways to identify drug users via behavioral testing and analytical techniques, reviews the approaches used by different countries, screening and confirmation techniques, alternative specimens (e.g., urine, oral fluid, sweat), and how rapid roadside testing could be coupled with behavioral and laboratory testing in an effective approach to identifying and prosecuting drugged drivers; (4) Driving Under the Influence of Drugs [DUID] Laws—provides an overview of DUID laws in the United States and Europe, discusses the basic tenets of these laws, the various types of DUID statutes, the reasons why many existing laws hinder the prosecution of drugged drivers and the rationale for developing per se legislation as a strategy to more effectively manage the drugged driver problem.

The Relationship between Benzodiazepine Use and Traffic Accidents: A Systematic Literature Review

In many countries, benzodiazepines are the most commonly used and misused psychoactive medicinal drugs. Results of epidemiological studies investigating the association between benzodiazepine use and traffic accidents seem to be inconclusive or inconsistent at first sight. However, the outcome of epidemiological studies may be influenced by several methodological factors like study design, study population, exposure measurement, outcome definitions and possible confounders.Our objective was to conduct a systematic literature review of epidemiological studies that investigated the association between benzodiazepine use and traffic accidents, including related outcomes like culpability and injury or accident severity. We searched EMBASE, PubMed and Forensic Science Abstracts 3/0 (FORS®) for references included in these databases at 1 June 2009 using the term ‘benzodiazepines’ in combination with ‘driving performance’ or ‘accident risk’ or ‘traffic accident’. For inclusion in this review, the study design had to be comparative, include road users involved in accidents and provide specific data about benzodiazepines. Sixty-six studies were included in the review. The study populations varied from the general (driving) population, accident-involved road users with or without injury and persons admitted to a hospital to fatally injured accident-involved drivers. Exposure assessment was performed by using toxicological results, prescription data or questionnaires.The divergent study populations and comparison groups and the variety of methods used to express the outcome of interest hampered comparison between results.Evidence is growing that exposure to benzodiazepines is related to increased accident risk. The literature indicates that the greatest accident risk is associated with the use of long half-life benzodiazepines, increasing dosage and the first few weeks of use of benzodiazepines. Clear evidence of increased culpability associated with benzodiazepine use is scarce. More research has to be done to elucidate the relationship between benzodiazepine use and injury severity.

The role of albumin conformation in the binding of diazepam to human serum albumin

The effect of hydrogen, chloride and calcium ions on the binding of diazepam to human serum albumin has been studied by circular dichroism and equilibrium dialysis. In all cases the molar ellipticity of the diazepam-albumin complex increases with pH over the pH range 5 to 9. Under these conditions the free concentration of diazepam at a constant low drug to protein ratio decreases with pH. This free concentration is higher in the presence of chloride and calcium ions. With a two state conformational model for albumin it was shown, that the pH dependences of molar ellipticity of the diazepam-albumin complex and of the free concentration of diazepam are linked. It was demonstrated that the N-B transition of albumin is involved in the pH dependent binding of diazepam. The consequences of these findings for equilibrium dialysis procedures in determining free plasma levels of diazepam are discussed.

Road traffic accidents and psychotropic medication use in the Netherlands: a case-control study

AIM To examine the association between the use of commonly prescribed psychotropic medications and road traffic accident risk. METHODS A record-linkage database was used to perform a case-control study in The Netherlands. The data came from three sources: pharmacy prescription data, police traffic accident data and driving licence data. Cases were defined as drivers, who had a traffic accident that required medical assistance between 2000 and 2007. Controls were defined as adults, who had a driving licence and had no traffic accident during the study period. Four controls were matched for each case. The following psychotropic medicine groups were examined: antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants stratified in the two groups, SSRIs and other antidepressants. Various variables, such as age, gender, medicine half-life and alcohol use, were considered for the analysis. RESULTS Three thousand nine hundred and sixty-three cases and 18,828 controls were included in the case-control analysis. A significant association was found between traffic accident risk and exposure to anxiolytics (OR = 1.54, 95% CI 1.11, 2.15), and SSRIs (OR = 2.03, 95% CI 1.31, 3.14). A statistically significant increased risk was also seen in chronic anxiolytic users, females and young users (18 to 29 years old), chronic SSRI users, females and middle-aged users (30 to 59 years old), and intermediate half-life hypnotic users. CONCLUSIONS The results of this study support previous findings and confirm that psychoactive medications can constitute a problem in traffic safety. Both health care providers and patients should be properly informed of the potential risks associated with the use of these medicines.

Prescribing and Dispensing Guidelines for Medicinal Drugs Affecting Driving Performance

This chapter aims to provide practice-oriented information for prescribing physicians and dispensing pharmacists who want to provide their patients with adequate advice based on a clear understanding of the risks of accident involvement under different treatment conditions. Specific attention will be given to the application of a graded-level warning system based on categorization systems for psychotropic medicines that have been introduced,, and sometimes legally implemented, in several European countries. This warning system allows physicians and pharmacists to select the least impairing medicines within a therapeutic class. Advice for the patient based on three categories has been described in clear instructions, allowing the patient to make the right decision.

The concentration of oxazepam and oxazepam glucuronide in oral fluid, blood and serum after controlled administration of 15 and 30 mg oxazepam

AIMS To measure and compare the concentration-time profiles of oxazepam and oxazepam glucuronide in blood, serum and oral fluid within the scope of roadside testing. METHODS Biological samples were collected from eight male subjects after ingestion of 15 or 30 mg oxazepam on separate dosing occasions with an interval of 7 days. The concentration-time profiles of oxazepam and oxazepam glucuronide were fitted by using a one-compartment model. RESULTS For oxazepam and oxazepam glucuronide, the mean oral fluid/blood ratios were 0.05 (range 0.04-0.07) and 0.004 (range 0.002-0.006), respectively. The concentration-time profiles in oral fluid paralleled those in blood. CONCLUSION After oral administration of therapeutic doses of oxazepam, concentrations in oral fluid are very much lower than those in blood, and those of oxazepam glucuronide are much lower than those of the parent compound. Nevertheless, assay of oral fluid for oxazepam can be used to detect recent ingestion of the drug in drivers suspected of impaired driving performance.

A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

The use of driving impairing medicines: a European survey

AimTo analyse the consumption of a number of medicines with a known potential for increasing the risk of road traffic accidents in the general population of Europe.MethodsQuestionnaires were distributed through the European Drug Utilization Research Group (EuroDURG) and Post-Innovation Learning through Life-events of drugs (PILLS) networks. A total of 30 countries (the current EU Member States, Iceland, Norway and Switzerland) were asked to supply data on the use of driving impairing medicines for the period 2000–2005, aggregated at the level of the active substance and presented in Defined Daily Doses (DDDs) per 1000 inhabitants per day.ResultsNational utilization data were provided by 12 of the 30 countries. Based on these data, a considerable increase in consumption was only seen for the antidepressants and the selective serotonin reuptake inhibitors. A slight increase, decrease or no increase was seen for the rest of the drugs studied (i.e. opioids, antipsychotics, anxiolytics, hypnotics and sedatives, drugs that are used in addictive disorders and antihistamines). Limitations were encountered when data on driving impairing medicines were compared between countries (e.g. variation in the data sources and providers, population coverage, inclusion of hospital data, use of divergent ATC/DDD versions) and, therefore, a cross-national comparison could not be performed.ConclusionsDuring the study period, trends within countries showed slight to no increase in the consumption of selected medicinal drug groups, with the exception of the antidepressants and the selective serotonin reuptake inhibitors: they showed a remarkable increased use during the study time-frame. Our results illustrate that it is still difficult to perform a valid and comprehensive collection of drug utilization data on driving impairing medicines. Therefore, efforts to harmonize data collection techniques are required and recommended.

Evidence for distinct consecutive steps in the neutral to base transition of human serum albumin

The neutral to base transition in human serum albumin has been studied by means of circular dichroism and equilibrium dialysis using nitrazepam as the non-covalently bound circular dichroic probe. Spectroscopically two transitions were observed over the pH range 5.5-8.5, whereas dialysis data point to only one transition occurring in the latter part of the pH region studied. Both pH dependences could only be correlated if it is assumed that the neutral to base transition consists of at least two distinct consecutive steps.

Influence of the use of functional foods enriched with phytosterols/-stanols on adherence to statin therapy

Subjects using functional foods with approved health claims may be more likely to be non‐adherent with prescribed drug therapy. This study aimed to assess the influence of the use of phytosterol/‐stanol‐enriched functional foods on adherence to statin therapy among patients initiating treatment.