Pharmacodynamic and Pharmacokinetic Causes
The mechanisms that lead to desensitisation can be conveniently divided into two general groups (Fig 3). In the first group, there may be a reduction in the pharmacodynamic effectiveness of the drug in spite of the plasma and tissue concentrations being unchanged. This group can be further divided into those that are receptor-mediated and those that are non-receptor-mediated. In the second group, there may be a reduction in the plasma and tissue drug concentrations that result from the same drug dose because of alterations in the way the drug is handled (its 'pharmacokinetics').
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Fig 3 Factors causing desensitisation to the effects of drugs can be divided into those that affect the relationship between drug dose and subsequent concentration (pharmacokinetic causes) and those affecting the relationship between concentration and effect (pharmacodynamic causes).
