Handbook of Drug Interactions

440 Jones
Table 9
Top 10 Drugs Identified in Medical Examiner Cases and in Impaired Drivers in Sweden
Rank Medical Examiner Cases a Impaired Drivers b
1 Ethanol Ethanol
2 Acetaminophen Amphetamine
3 Diazepam + nordiazepam Tetrahydrocannabinol
4 Propoxyphene Diazepam + nordiazepam
5 Morphine c Flunitrazepam + 7-amino flunitrazepam
6 Citalopram Morphine c
7 Codeine Methamphetamine
8 Propiomazine Codeine
9 Carbon monoxide Acetaminophen
10 Zopiklone MDMA (Ecstacy)
Many of these substances occur in combination with ethanol, the number one drug in both lists.
a Femoral venous blood.
b Cubital venous blood.
c Metabolite of heroin and codeine.
to drugs also includes a strong genetic component (460). There are marked racial and
ethnic differences in phase I drug-metabolizing enzymes, and CYP2D6, CYP2C9,
and CYP2C19 show polymorphism, which not only influences the rate of metabolism
of drugs but also helps explain the large variability in plasma concentrations and therapeutic
response of the particular medication (461–465). The subject of pharmacogenetics
of drug action and interaction has emerged as a hot research topic and the notion
of manufacturing tailor-made drugs based on genetic profiling of the individual is
something for the future (466,467). If this becomes a reality, perhaps adverse effects
of drugs and undesirable drug–alcohol interactions could be avoided (466). The alcohol
flush reaction seen in many Asians when they drink alcohol is a direct result of the
inactive form of ALDH they inherit that makes them highly sensitive to acetaldehyde
produced during metabolism of ethanol. This adverse reaction protects them from
becoming heavy drinkers and alcoholics and is a good example of a pharmacogenetic
trait (468).
Much of the variability in pharmacokinetics of ethanol can be explained by a combination
of genetic and environmental factors as well as the experimental design of the
studies (469). Such things as the route and timing of administration of ethanol and drugs
and the selection and allotment of subjects to test and control groups will influence
outcome of the study. More work is needed to investigate variability in pharmacokinetics
and pharmacodynamics of ethanol and drug–alcohol interactions in real-world drinking
situations with repeated intake of different kinds of alcoholic beverages without
reference to body wt or previous exposure to drugs.
Confusion and controversy exist regarding the reality of certain drug–alcohol
interactions. Animal studies are often not very helpful in elucidating the problem and
such articles have not been cited or considered in this review. Many older studies purporting
to find a significant metabolic or CNS interaction between ethanol and a partic-