It depends on the drug, but various methods exist. A few non-MDR mechanisms include: mutated target enzyme, decreased drug activation or increased drug degradation (due to altered metabolism), drug inactivation due to increased conjugation with glutathione, redistribution inside the cell, drug interactions, increased DNA repair, failure to die by apoptosis, alteration in the targeted signalling pathway.
Drug resistance occurs because of a decreased quantity of the substance reaching the site it affects. This may be caused by an increase in induction of the enzymes (CYP450 enzymes) required for degradation of the drug.
Reduced responsiveness: the response to the substance is decreased by cellular mechanisms. This may be caused by a down regulation of receptor numbers.
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