Dispositional tolerance

Drug tolerance has been described and studied for years, but only recently have experiments begun to reveal its complexity. In secondary texts, until the past few years, tolerance has been partitioned into dispositional and pharmacodynamic subgroups (e.g., Jaffe, 1985; see Overstreet & Yamamura, 1979). Dispositional tolerance exists when the body's ability to dispose of the drug becomes enhanced over repeated trials. This may mean that the liver more easily degrades the drug or that the kidney more readily excretes it into the urine. Ultimately it means that less of a given dose of a drug ever reaches critical sites within the body, and the drug effect is therefore smaller. Pharmacodynamic (sometimes called functional) tolerance exists ifa constant amount of a drug reaches some critical organ or tissue but the response of that organ or tissue is reduced. Such tolerance is often described in terms of altered receptor numbers or affinity, changes of available neurotransmitters, and the like (Overstreet & Yamamura, 1979). The bottom line is that drug tolerance has been logically and conveniently considered to represent a reduction in the amount of the drug that reaches critical target organs, or a dulling of the responsivity of those same target organs, or both. Although these possibilities are not mutually exclusive, they were taken to be exhaustive. A smaller net drug effect could be a result of a lower amount of the drug or to decreased sensitivity to the drug. (Woods 1991, 488 --489)

References

Woods, Stephen C. 1991. “The eating paradox: How we tolerate food.” Psychological review 98 (4): 488–505. doi:10.1037/0033-295X.98.4.488.