Hysteresis clockwise

Fig. 8. Relationship between natriuresis and furosemide excretion rate. The first observation representing counter-clockwise hysteresis has not been included in the fitting of the sigmoid max model. (From Wakelkamp M. Furosemide dosage input - consequences for diuretic effect, tolerance and efficiency. Diss. Karolinska Institutet, Stockholm 1997.)...

Drug distribution does not constitute the sole explanation for the appearance of a counter-clockwise hysteresis. Another reason may be that once the drug has reached its site of action, the cascade of receptor-related and post-receptor events leading to the measured drug effect takes time to develop and lags... 

Let us now take normal conditions. For CO oxidation over Pt catalysts, sufficiently complete studies have been carried out to identify the dependence of the reaction rate on the CO concentration VF(Cco) and temperature JF(T). For these dependences we can observe specific critical effects. They are the clockwise hysteresis for VF(Cco) and counter-clockwise hysteresis for W(T). It is these characteristics that we have obtained for the kinetic model of the adsorption mechanism. 

It has already been noted that counter-clockwise hysteresis can also exist in W(C02). Just this peculiarity has been found experimentally in the above parametric range (Fig. 32). 

Maxwell-Wagner piezoelectric relaxation and clockwise hysteresis... 

Figure 13.6 Piezoelectric coefficient d and tan<5p of a single phase Bi4Ti30i2 ferroelectric ceramic with highly anisotropic grains, at room temperature. On the right are shown charge-pressure hysteresis loops at selected frequencies, with a clockwise hysteresis at 0.07 Hz and counter-clockwise hysteresis at 70 Hz. See [17] for details.

Under the assumptions of the direct-link model, neither a counterclockwise (Figure 10.2) nor a clockwise hysteresis loop (Figure 10.4) will be recorded in an effect vs. concentration plot. In principle, the shape of the effect vs. concentration plot for an ideal direct-link model will be a curve identical to the specific pharmacodynamic model, relating effect with concentration, e.g., linear for a linear pharmacodynamic model, sigmoid for the sigmoid Emax model (cf. Table 10.1 and following paragraphs and sections), etc. 

Figure 10.4 Normalized effect-plasma drug concentration state space for tolerance phenomena. As time flows (indicated by arrows) a clockwise hysteresis loop is formed.

During repeated oral administration of dofetilide 1.0-2.5 mg/day for 5 days the effect on the QT interval was slightly greater on day 1 than on day 5 at a range of plasma concentrations of about l ng/ml this observation suggests the occurrence of tolerance, but in that case one would have expected a clockwise hysteresis loop in the effect concentration curve, and no hysteresis was seen either after a single dose or at steady state (25). 

Another situation in which the plasma concentration-effect relationship may be confounded by time is one where there is very rapid development of tolerance to the drug, even within a single dosing cycle. In this case, for a given plasma concentration, drug effect will be lower as concentrations are falling than when they are rising and will produce clockwise hysteresis this has been demonstrated for nicotine. 

FIGURE 20.8 The left panel shows a typical versus Effect plot for a drug obeying a simple max relationship. The right panel shows the clockwise hysteresis seen in the G vesus Effect plot when drug tolerance is present. The arrows represent the progression of time. 

FIGURE 5-17. Hysteresis occurs when effect measurements are different at the same concentration.This is commonly seen aftershort-term intravenous infusions or extravascular doses where concentrations i ncrease and subsequently decrease. Counterclockwise hysteresis loops are found when concentration-effect points are joined as time increases shown by arrows) and effect is larger at the same concentration but at a later time. Clockwise hysteresis loops are similar, but the concentration-effect points are joined in clockwise order and the effect is smaller at a later time. 

Investigations have revealed that ankle quasi-stiffness and hysteresis change as gait speed changes. Moment-angle curves in the ankle joint have clockwise hysteresis loop at... 

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