= Drug tolerance
<Drug tolerance> is a reduced response to a specified exposure after repeated exposure. Comparison requires defining the endpoint and concentration: a smaller response at the same administered amount can also arise because <drug metabolism> has increased and target exposure has fallen. Cellular adaptation at unchanged exposure is a different mechanism. <FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class>[2020 safety communication: dependence, withdrawal and adaptation during repeated use]{ref}
In a concentration–response experiment, tolerance may appear as a shift toward higher concentrations, a lower maximum response or both. Different effects of one <drug> can adapt at different rates. This is why preserved response on one endpoint does not prove absence of tolerance on another, and why <drug tolerance> does not itself establish addiction or a withdrawal syndrome.
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