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Pharmacology intersects with toxicology when the physiological response to a drug is an adverse effect. A poison is any substance, including any drug, that has the capacity to harm a living organism. Poisoning generally implies that damaging physiological effects result from exposure to pharmaceuticals, illicit drugs, or chemicals.
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Abbreviations
ADEs: adverse drug events
ADME: absorption, distribution, metabolism, and elimination
CYP: cytochrome P450
ECG: electrocardiogram
ED50: median effective dose
FDA: U.S. Food and Drug Administration
GI: gastrointestinal
Ig: immunoglobulin
IND: investigational new drug
IRB: institutional review board
LD50: median lethal dose
SSRI: selective serotonin reuptake inhibitor
TI: therapeutic index
WBI: whole-bowel irrigation
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Conventional Dose-Response Curves
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There is a graded dose-response relationship in an individual and a quantal dose-response relationship in the population (see Figures 3–2, 3–3, and 3–6). Graded doses of a drug given to an individual usually result in a greater magnitude of response as the dose increases. In a quantal dose-response relationship, the percentage of the population affected increases as the dose is increased; the relationship is quantal in that the effect is judged to be either present or absent in a given individual. This quantal dose-response phenomenon is used to determine the LD50 of drugs, as defined in Figure 4–1A.
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One can also determine a quantal dose-response curve for the therapeutic effect of a drug to generate ED50, the concentration of drug at which 50% of the population will have the desired response, and a quantal dose-response curve for lethality by the same agent (Figure 4–1B). These two curves can be used to generate a TI, which quantifies the relative safety of a drug:
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Clearly, the higher the ratio, the safer the drug.
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