MEDizzy - When evaluating the effects of certain adrenergic agonists

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General pharmacology

When evaluating the effects of certain adrenergic agonists in a variety of in vitro and in vivo models, we find that the responses exhibit the phenomenon of tachyphylaxis. Which of the following best describes what the term tachyphylaxis means?

ExplanationTachyphylaxis is defined as rapidly developing tolerance to the effects of an agonist that is administered repeatedly, even if the subsequent dosages are not changed or they may actually be progressively increased. It is sometimes also called desensitization or down-regulation of the receptor(s). The mechanism behind the phenomenon varies, and to a degree depends on which drug (or agonist) is being used, and what the target (effector) is. For example, frequent and repeated exposure of receptors to a drug may change (at least temporarily) the conformation of the receptor to one that is less able to bind further drug. In systems that require quick synthesis of new receptors, repeated exposure to agonist may occur at such frequent intervals that there is inadequate time for new receptors to be made. Two good examples are the diminished response (of a variety of cells/tissues) to repeated administration of amphetamine, which acts by releasing neuronal norepinephrine. Challenge the system repeatedly, and the amount of intraneuronal NE available to be released—which is essential for causing the ultimate response—goes down. Another example, with more clinical relevance, is the rapid development of “tolerance” of airway smooth muscles and their ability to relax (i.e., cause bronchodilation) in response to repeated administration of β-adren- ergic agonists, such as albuterol, arguably the most widely used adrenergic bronchodilator for asthma. This tolerance—often developing quickly enough to be called tachyphylaxis—is one of the pitfalls of managing asthma, mainly with adrenergic bronchodilators, particularly if they are administered too often and at increasing dosages. (Note: There is no “magical” number—hours or days, for example— that distinguishes between tachyphylaxis and “regular” tolerance. The brevity which the tolerance develops is the key point.)