Lecture 4

Question 1

What is cross-tolerance?

Answer 1

Becoming tolerant to one member of a class (f.e. opioids, adrenergic agonists, nasal sprays), will cause one to become tolerant to all drugs within the class
-> because they share mechanisms of action (MOA)

-f.e. used a lot of oxycodone and now try hydrocodone but still does not have much effect due to cross tolerance

Question 2

What is Tachyphylaxis?

Answer 2

Rapid tolerance (f.e. nasal sprays for congestion, pollen allergy)

Question 3

What is Sensitization?

Answer 3

-requires lower dose with repeated use
-shift to the left on the drug-response curve
-f.e. alcohol -> first tolerance is built, then the ability of the liver to metabolize alcohol decreases -> Sensitization (less alcohol needed to get drunk)

Question 4

Which mechanism causes Sensitization?

Answer 4

-Pharmacokinetics: the liver is not able to metabolize the alcohol

(-Behavioral sensitization)

Question 5

How to find KD? = How to find the drug concentration needed to occupy 50% of receptors?

Answer 5

-find the drug dose needed to reach 100% drug-receptor complexes [DR] –> also [R total] (all receptors used
-find the drug concentration needed to reach 50% of [R] = KD

Question 6

What does KD indicate?

Answer 6

KD is a measure of the drug’s affinity to the receptor
-> on a drug-response plot it would be more to the left

-the lower the KD, the higher the affinity
-KD is INVERSELY related to Affinity –> 1/ KD

Question 7

What is a prototype?

Answer 7

A drug that represents a drug class
-similar chemical structures and MOA

Question 8

What is IC50?

Answer 8

-approach to see how well the drug binds to the binding site of the receptor
-the concentration of inhibitor needed to decrease [DR] from 100% to 50%

Question 9

Formula for KI

Answer 9

IC50 / 1 + [D*] (known KD) / KD

Question 10

How does KI relate to the affinity of an Inhibitor to the binding site of a receptor?

Answer 10

the lower the concentration of the Inhibitor needed to reach 50% (from 100%) the higher the affinity of the inhibitor to the receptor = the lower KI, the higher the affinity of the inhibitor to the receptor (seen when IC50 is implemented into the KI formula)

Question 11

What do the binding data from KD and KI indicate about the efficacy of an Agonist?

Answer 11

It indicates how well something binds, but it doesn’t tell anything about the efficacy (f.e. we won’t know how efficacious an unknown Agonist is)