Drug interactions
In the majority of cases in clinical and forensic toxicology, more than one drug is involved. Multidrug therapy and abuse is prevalent and this, together with the added problems of self-medication with over-the-counter drugs and the widespread use of alcohol, makes interpretation of data even more complicated. Pharmacokinetic and other data available in the scientific litera ture often refer to drug concentrations and responses observed after administration of the drug alone. In practice, when these data are compared with analytical results that involve several drugs, it must be remembered that the clinical response is often a consequence of the combined actions of more than one drug. If the significance of the analytical results is to be assessed correctly, it is essential to consider the quantitative effects of any interactions that might occur between drugs taken in combination. Drug interactions can be divided into two types:
• those that affect the drug concentration (i.e. alter the processes of absorption, distribution and elimination)
• those that affect the response (by changing its duration and severity). The consequences of most drug combinations can be predicted with knowledge of the usual effects of drugs.
Drugs with opposite pharmacological activities (e.g. barbiturates and amfetamines) may have an antagonistic effect. Conversely, the additive effects or side-effects of two drugs with the same pharmacological action (e.g. central nervous system depressants) may prove fatal even though the individual drug concentrations are not toxic themselves. Further, a drug with a high affinity for tissue proteins might displace a second drug from binding sites, while a drug that changes urinary pH or that competes for the same active transport system in the proximal tubules of the kidney might inhibit renal excretion. Other important mechanisms for drug interactions include:
• interference with absorption of other drugs
• modification of rates and routes of metabolism
• changing the accessibility of receptors and tissue sites.
