Tolerance development as a pharmacological and clinical problem.

Two main forms of acquired pharmacological tolerance may be distinguished, dispositional (pharmacokinetic) and pharmacodynamic. Pharmacodynamic tolerance is common, and can in many cases be attributed to adaptive receptor changes. Such changes of beta-adrenoceptors have been extensively studied and widely used as models for explaining the mechanisms of tolerance development. The mechanisms behind tolerance to adrenoceptor agonists are discussed, and also tolerance development to these and some other agents when used in the treatment of asthma, uterine hyperactivity and congestive heart failure.