CARDIOVASCULAR RESPONSES DURING AMPHETAMINE TACHYPHYLAXIS

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle 5, Washington

Peripheral blood flow experiments have shown that amphetamine when injected locally or systemically causes a prolonged decrease in flow, but that these effects reach a limit beyond which further administration of the drug produces no further constrictive effect. At this time, locally administered epinephrine is still capable of stopping flow completely.

With the onset of amphetamine saturation with respect to vasoconstriction, subsequent intra-arterial injections of amphetamine result in a transient vasodilation to which tachyphylaxis does not develop.

Because systemic responses to intravenously injected amphetamine are not impaired by "saturating" intra-arterial doses, it may be said that a local "tachyphylaxis" to amphetamine readily follows the intra-arterial injection of this drug.

The effect of either single or repeated intravenous doses of amphetamine causes a progressive decrease in cardiac output and a progressive increase in total peripheral resistance.

Amphetamine tachyphylaxis in the anesthetized dog is a phenomenon of accumulative saturation of vascular receptors by amphetamine, general blood pressure failing to parallel vascular effects because of concomitant compensatory mechanisms.