Consequences of drug concentration changes (Introduction) (Human Drug Metabolism)

If there are large changes in the rate of removal of a drug, then this can lead in extremis to severe problems in the outcome of the patient’s treatment: the first is drug failure, whilst the second is drug toxicity (Figure 1.2). These extremes and indeed all drug effects are directly related to the blood concentrations of the agent in question.

Drug toxicity

If a drug accumulates for any reason, either by overdose or by a failure of drug removal, then serious adverse reactions will result. A reduction in the rate of removal of the drug from a system (often due to administration of another drug), will lead to drug accumulation. Toxicity can be an intensification of a drug ’ s therapeutic action, or an unrelated damaging effect on a tissue or organ system. If the immunosuppressive cyclosporine is allowed to accumulate, severe renal toxicity can lead to organ failure. Excessive levels of anticonvulsant and antipsychotic drugs cause confusion and drowsiness, whilst the accumulation of the antihistamine terfenadine, can lead to lethal cardiac arrhythmias. In contrast to drug failure, drug toxicity may occur much more rapidly, often within hours rather than days.

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