Lecture 18

Question 1

“Touchstone Drugs”

Answer 1

• Ciprofloxacin inhibits topoisomerase enzymes (doesn’t affect human versions since ours are more advanced)
• Methadone is a mu-receptor agonist
• Methotrexate inhibits DHFR by competing with folate at the active site

Question 2

Antagonists

Answer 2

• Bind with receptor and DON’T activate
• Blocks activity of agonist
• Ability to displace agonist from receptor and prevent agonist-stimulated response
• Can be competitive, irreversible (suicide), allosteric, or inverse

Question 3

IC50

Answer 3

• Antagonist concentration that displaces 50% of the agonist or blocks 50% of the response
• How much antagonist it takes to displace the agonist
• Ki = Kd for inhibitors
• Found by graphing Agonist Receptor Binding v.s. log[Agonist]

Question 4

Competitive Antagonsim

Answer 4

• Reversible receptor binding
• Decreases agonist binding and agonist stimulated response
• Inhibition is overcome with sufficient agonist concentrations
• Shifts dose response curve to right (Graphs of Response v.s. log[Agonist])

Question 5

Competitive Antagonism response depends on… (2)

Answer 5

1. Relative affinities of agonist and antagonist for a receptor
2. Relative concentrations of agonist and antagonist

Question 6

Clinical Implications of Competitive Antagonism

Answer 6

• Degree of inhibition produced by competitive antagonist depends on antagonism concentrations
• Clinical response to competitive antagonist depends on endogenous concentrations of agonist that is competing for binding

Question 7

Irreversible Antagonism

Answer 7

-Removes receptor from active pool
-High dose of agonist can’t overcome the binding
-Blocks binding of agonist and stimulated response
-Reduces max response and shifts the drug response curve to the right (Response v.s. log[Agonist])
-Suicide/”assassin” drugs
EX: Aspirin, irreversibly binds to COX and remains that way until platelet is broken down. Increases bleeding since platelets don’t have DNA to make new COX

Question 8

Irreversible Antagonist Pros (2) & Cons(2)

Answer 8

Pros

1. Long duration
2. Effective in drug resistance

Cons

1. Safety
2. Off target effects (and possible mistakes) are also irreversible