Anesthetics and Foreign Tranquilizers: Tranquilizers
Last modified: Monday, 9. March 2015 - 8:28 am
In this short review, the term tranquilizer is used for three classes of drugs: neuroleptics, antidepressants, and anxiolytics. Including the antidepressants under the term tranquilizer may seem controversial, but in the medical practice they are often used in the treatment of neurotic outpatients for indications similar to neuroleptics and anxiolytics.
From the epidemiological point of view, the role of tranquilizers in traffic is obscure at the moment (). I have earlier pointed out in two reviews () that studies concerning the influence of tranquilizers on the numbers of fatal accidents do not demonstrate a clear overrepresentation of users of these drugs among the participants. However, the only hospital study available so far (which concerns the prevalence of diazepam, the most commonly used anxiolytic, among participants in personal injury accidents) demonstrates a clear overrepresentation of the drug users.
This seemingly controversial result may eventually appear quite logical when attention is paid to the populations represented in the two types of studies as related to the population of drug users. Participants in fatal accidents are mostly young males, who seldom use tranquilizers–at least for therapeutic purposes–whereas participants in personal injury accidents are more often from other groups of drivers. The fatal accidents often take place late on weekend nights, whereas the personal injury accidents are more evenly distributed throughout the week and often happen during the early hours of the evening. Tranquilizers are used mainly by elderly and middle-aged persons. Females use tranquilizers more often than males. As drivers, these persons are relatively seldom on the roads during the times when most fatal accidents occur. They may also be at a smaller risk of speeding and of driving under the influence of alcohol, two common features in fatal accidents.
Conclusions from the data above may not be very reliable, however, since the studies concerning the fatal accidents have mainly been conducted in the United States, and the hospital study was conducted in Oslo, Norway. Therefore, there is an obvious need for a series of epidemiological studies concerning the role of tranquilizers in personal injury and property damage accidents, Such a series of studies should in an optimum case be conducted in several countries at the same time and under the guidelines of an international organization such as OECD or IDBRA. This would enable the comparison between different countries of the consumption statistics of these drugs as related to their role in traffic accidents. These figures also would reveal some aspects of the prescription habits of the physicians in these countries and, if used correctly, could modify these habits later on. After all, tranquilizers are prescription medications, and their use is under the control of the medical profession. If tranquilizers have a significant role in property damage and personal injury accidents, this role can be diminished only through a fruitful cooperation with the medical profession.
Most recent laboratory studies concerning tranquilizers and driving have been discussed by Dr. I. Saario in the summary of his M.D. thesis (). Different kinds of impairments of psychomotor skills have been observed after use of the different classes of tranquilizers. This is as expected, when the pharmacology of the diverse drugs classified as tranquilizers is taken into account. Laboratory studies have indicated that the relationship between the levels of the drugs in biological specimens (such as blood, plasma, or urine) and their effects is much more complicated than that between blood alcohol levels and their effects. This is because most of the tranquilizers have multiple active metabolites, which may have a role in their adverse effects. The development of tolerance to the effects of tranquilizers is much stronger than that toward alcohol. The phannacokinetics of the tranquilizers are also much more complicated than those of alcohol. Structurally, closely related tranquilizers may have major differences in their pharmacokinetics, depending on factors such as water solubility, pKa, etc.
Taking into account the above discussion, it seems hard to develop legislation concerning tranquilizers and driving which would be equivalent to the present drinking and driving laws in the United States; i.e., any legal limits of plasma tranquilizer concentrations are extremely hard to define. What can be done in the future concerning tranquilizers and driving? The role of tranquilizers in traffic accidents has to be established, as suggested above. If a significant role is found, then studies should be directed in the following manner.
- 1. Controlled laboratory studies should be conducted to study the influence of the following factors on the effect of tranquilizers on psychomotor skills: age, sex, personality, and mental illness. The psychomotor skills measured should include choice reaction, coordination, divided attention, vigilance, and memory functions, as well as information sampling.
- 2. Best possible correlations between the pharmacokinetics of the drugs and their metabolites and psychomotor performance should be searched. In this context, a very important variable has turned out to be the duration of treatment.
- 3. Simple clinical tests for the measurement of skills related to driving should be developed.
- 4. Tests concerning the effects of drugs on skills related to driving should be included in the premarketing testing of tranquilizers and certain other drugs that are going to be used mainly for the treatment of outpatients.
- 5. Use of tranquilizers should be limited to those patients who really need them. Present consumption statistics suggest that many relatively healthy persons use tranquilizers; fewer of these people should take them.
- 6. Since we have recently demonstrated a fairly strong state-dependent effect of diazepam (), training the drug users in how to manage in traffic under the influence of the tranquilizers may become a useful means of reducing the possible accident risk caused by these drugs.