ETX 30-3 - Environmental Toxicology 30 Topic Dose Response...

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Environmental Toxicology 30 Chemical Use and Abuse Topic: Dose Response I. Receptors and Dose-Response: Law of Mass Action a. Receptors and Dose Response i. The dose response curve is a graphical representation of a drug effect as a function of concentration at receptor site. ii. [D] + [R]  [DR] Effect b. Receptor Binding i. Reversible ii. Most drug-receptor interactions involve multiple weak bonds. iii. Good or bad? c. Law of Mass Action i. Paul Ehrlich and JN Langley: formulation of receptor theory at end of 19 th /beginning of 20 th century. ii. AJ Clark 1933: The mode of action of drugs on cells Developed mathematical relationship of drug receptor interactions that follow the Law of Mass Action and was based on the reversible absorption of a gas to a metal surface. iii. Illustrated by a hyperbolic curve- Langmuir adsorption isotherm. iv. B-total concentration of substance v. S- concentration of substance absorbed d. Dose Response Curves i. Plot of dependent variable, response or effect against the independent variable, dose ii. Arithmetic concentration (left) iii. Log concentration (right) e. Log Dose-Response curves i. Linear region cover 20-80% of the maximum response ii. Apparent binding constants can be measured, Kd iii. Dissociation constants for drugs are in the nM (10 ⁻⁹ M) range, implying high affinity iv. Measure concentration of drug required to cause half of the maximal response II. Graded Responses a. A graded response occurs on a continuous scale and response is proportional to the number of receptors occupied.
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