Tachyphylaxis, indirect sympathomimetics

Indirect sympathomimetics (B) are agents that elevate the concentration of NE at neuroeffector junctions, because they either inhibit re-uptake (cocaine), facilitate release, or slow breakdown by MAO, or exert all three of these effects amphetamine, metham-phetamine). The effectiveness of such indirect sympathomimetics diminishes or disappears (tachyphylaxis) when ve-Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

The indirect sympathomimetic drugs can be used clinically for systemic or local vasoconstriction. Since the mechanism is an increase in the noradrenaline concentration there are always jSi-adrenoceptor-mediated effects like tachycardia and extrasystoles. Since the re-uptake of noradrenaline is necessary to sufficiently refill the axonal vesicles, a frequent use of indirect sympathetic drugs results in a loss of efficacy by transmitter exhaustion. This phenomenon of use-dependent loss of effect is called tachyphylaxis. 

NE in the opposite direction, that is, to liberate it into the extracellular space. Thus, amphetamine promotes a nonexocytotic release of NE. The effectiveness of such indirect sympathomimetics diminishes quickly or disappears (tachyphylaxis) with repeated administration. 

Tachyphylaxis refers to a quickly developing tolerance brought about by the rapid and repeated administration of drugs. For example, indirect-acting sympathomimetic agents such as tyramine, which exert their effects through the release of norepinephrine, are able to cause tachyphylaxis. If norepinephrine is not present, tyramine fails to act until the supply of norepinephrine in nerve terminals has been replenished (Figure 3.3). 

Overuse of certain decongestants that are indirect-acting sympathomimetics can lead to a diminished response. Tachyphylaxis in such cases is most probably due to... 

Answer E. Tachyphylaxis, a rapid loss of pharmacologic activity, frequently occurs with indirect-acting sympathomimetics such as amphetamine, ephedrine, and pseudoephedrine. These drugs act to release NE from the mobile pool in sympathetic nerve endings. With excessive use of these agents, the NE stores may become depleted, resulting in a decreased response of vascular smooth muscle in terms of vasoconstriction. 

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