Skip main navigation

Indirect Link Model and Clockwise Hysteresis


The indirect link model stipulates a separate effect site outside the central compartment, and the drug distribution to that compartment causes the delay of effect. On the other hand, the model could imply a drug tolerance, typical for addictive substances. In such case, the effect-conc plot exhibits a counterclockwise hysteresis.

The indirect link model is typically characterized by a delay of effect, as shown in the case of diclofenac The delayed response can also be manifested as a counterclockwise hysteresis, where the peak effect trails the peak plasma concentration. At least in one case, insulin appeared to follow the hysteresis pattern. Noteworthy is the intoxication of cocaine, where the peak effect occurs before the peak plasma concentration. This counterclockwise hysteresis happens as a result of drug tolerance. The intoxicating effect of cocaine peaks early and dwindles as the concentration in the plasma rises.

This article is from the free online

Pharmacotherapy: Understanding Biotechnology Products

Created by
FutureLearn - Learning For Life

Reach your personal and professional goals

Unlock access to hundreds of expert online courses and degrees from top universities and educators to gain accredited qualifications and professional CV-building certificates.

Join over 18 million learners to launch, switch or build upon your career, all at your own pace, across a wide range of topic areas.

Start Learning now