Intro to Pharmacodynamics

Question 1

describe graded versus quantal dose-response

Answer 1

graded response: is a continuous scale (effect vs. dose) that is measured in a single biological unit that relates drug dose to the intensity of an effect (ex. increase dose, increase response)

quantal response: refers to all or none pharmacological effects (ex. life or death) and related the drug dose to the frequency of an effect

Question 2

list and describe the main pharmacodynamic parameters (3)

Answer 2

1. efficacy: the degree of the effect of the drug on the intended target
2. potency: relates what concentration of a drug is needed to produce a certain response
3. sensitivity: how steep the dose-response curve is (how quickly/effectively a drug achieves a response)

Question 3

describe therapeutic index and relate to drug selectivity

Answer 3

therapeutic index is the ratio of a toxic dose over the effective dose; you want a large therapeutic index so that way you can play around with efficacy and get that as high as possible without getting close to a toxic dose; determines drug selectivity, which is the most important parameter of pharmacodynamics as the ability to control toxicity is so vital, this is followed by efficacy, then by potency

Question 4

describe PK/PD modeling and its value

Answer 4

pharmacokinetics is what the body does to the drug, while pharmocodynamics is what the drug does to the body;

the advantage of plotting PK versus PD instead of dose versus PD is that it allows you to integrate the drug concentration over time with the drug effects, with less variation between subjects, allowing you to optimize the dose much more accurately as you are studying concentration versus effect

Question 5

describe a hysteresis loop

Answer 5

this occurs when you plot effect versus time instead of concentration versus effect because in this model the drug effects lag behind drug concentration in a counterclockwise loop known as hysteresis, which means that for any given concentration of a drug, the graph will tell you two possible effects since there are many steps that must happen with a drug before a response is observed

Question 6

describe the concept of bioequivalence and generics

Answer 6

in order for a generic drug to be considered bioequivalent to the pioneer, it must display a 20% or less difference in the mean AUC; this does not make an impact on effect if the drug is able to achieve max efficacy, however, if the therapeutic index is lower and the drug is less effective initially, a difference of 20% AUC could result in up to a 40% difference in efficacy, so generics aren’t always truly bioequivalent to the pioneers