Graded Dose-Effect Relationship

FIGURE 18.6 Graded concentration-effect curve for intravenous lidocaine in patients with neuropathic pain. Pain was scored from 0 to 10 with an analog pain scale. The median pretreatment pain score was 7 and a score of 0 meant no pain. Blood levels of lidocaine were measured every 10 minutes and pain was scored at the same time points. The graph relates the blood level of lidocaine to the severity of pain. (Adapted from data published by Ferrante FM, Paggioli J, Cherukuri S, Arthur GR. Anesth Analg 1996 82 91-7.) 

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Figure 18.2 illustrates a graded dose-effect relationship for recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease (2). Erythropoietin/ which is produced by the kidney in response to hypoxia/ is a naturally occurring hematopoietic growth factor that stimulates bone marrow production... 

Whereas a graded dose-effect relationship relates drug dose and concentration to the intensity of a... 

The Graded Dose-Effect Relationship Magnitude of Anemia as a Function of Chemical Dose in an Individual Rat... 

The effect of a substance depends on the amount administered, i.e., the dose. If the dose chosen is below the critical threshold (subliminal dosing), an effect will be absent. Depending on the nature of the effect to be measured, ascending doses may cause the effect to increase in intensity. Thus, the effect of an antipyretic or hypotensive drug can be quantified in a graded fashion, in that the extent of fall in body temperature or blood pressure is being measured. A dose-effect relationship is then encountered, as discussed on p. 54. 

Dose-effect relationship is the Relationship between the total amount of an agent administered to, taken up or absorbed by an organism, system or (sub) population and the magnimde of a continuously-graded effect to that organism, system or (sub) population. ... 

Therefore, we can identify two types of relationship with the dose of the toxicant a dose-effect relationship (graded effect) and a dose-response relationship (all-or-none effect). However, the term "dose-response relationship" is often used to describe both types. 

Figure 5.2 Graphical representation of the dose-effect relationship of SM. Bars represent graded reactions of different areas of the skin to SM vapour in humans. Reactions are compiled from US" and CDRE (India) reports for ranges of dosages specified. Severity 1 mild erythema 2 moderate erythema 3 intense erythema 4 erythema with oedema, maceration of axillary skin and dry desquamation 5 vesicle or numerous micro-vesicles or crusting and ulceration of the scrotum or axillae. Body areas abd abdomen arm arm ax axillae bt buttocks cf cubital fossae dth dorsal thorax ing inguinal region leg leg 1th lateral thorax neck neck pen penis pop popliteal fossae scr scrotum sh shoulder thi thigh vth ventral thorax wrt wrist.

For example, the industrial chemical hydrazine not only causes death, as a result of effects on the central nervous system, but also causes dysfunction in the liver, leading to the accumulation of fat. This effect is not related to the lethality, but it shows a clear relationship with dose. The response, that is, fatty liver, is a graded effect rather than an all-or-none response and can be quantitated either as an increase in liver weight (as percent of body weight) or by specific measurement of the triglycerides. Both measurements show a similar dose-effect curve (Fig. 2.2). 

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