FIGURE 5-4 Frequency distribution curves and quantal concentration—effect and dose-effect curves. A. Frequency distribution curves. An experiment was performed on 100 subjects, and the effective plasma concentration that produced a quantal response was determined for each individual. The number of subjects who required each dose is plotted, giving a log-normal frequency distribution (colored bars). The gray bars demonstrate that the normal frequency distribution, when summated, yields the cumulative frequency distribution—a sigmoidal curve that is a quantal concentration-effect curve. B. Quantal dose-effect curves. Animals were injected with varying doses of sedative-hypnotic, and the responses were determined and plotted. The calculation of the therapeutic index, the ratio of the LD50 to the ED50, is an indication of how selective a drug is in producing its desired effects relative to its toxicity. (See text for additional explanation.)
patient in the hospital and about 0.4% per each course of therapy. Adverse reactions to drugs are the most common cause of iatrogenic disease.
Mechanism-based adverse drug reactions are extensions of the principal pharmacological action of the drug. These would be expected to occur with all members of a class of drugs having the same mechanism of action.
When an adverse effect is encountered infrequently, it may be referred to as idiosyncratic (i.e., it does not occur in the population at large). Idiosyncratic adverse effects may be mechanism-based (e.g., angioedema on angiotensin-converting enzyme inhibitors) or off-target reactions (e.g., anaphylaxis to penicillin). Investigations of idiosyncratic reactions often have identified a genetic or environmental basis for the unique host factors leading to the unusual effects.
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