 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. ^[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.