Dose-response curves

What is the difference between a graded and quantal response?

• Graded

  • numerical value (HR, BP)

• Quantal

  • yes/no questions

How is the efficacy or Emax of a drug determined?

• determined by plateau of curve on graph

Define potency of a drug

conc/dose that produces HALF of the maximal response

How is the potency (EC₅₀ or ED₅₀) of a drug determined?

1. determine Emax

2. Find half the Emax

3. look at what dose produces half the Emax

T/F: Low ED₅₀ means lower potency

FALSE → higher potency

What happens to an agonist response in the response of an agonist that produces an additive response?

• increases response

• both agonists are active

What happens to an agonist response in the response of an agonist that produces a synergistic response?

• increases the response 3x

• both agonists are active

What happens to an agonist response in the response of an inactive substance that produces a potentiated response?

• increases response by 2x

• only one agonist is active, the other is inactive

What happens to an agonist response in the response of a ligand that is a competitive antagonist?

• reversible

• higher dose of agonist is needed to overcome antagonist effects

• dose response curve is shifted RIGHT

  • trying to shift to active receptors

• Emax is NOT reduced

What happens to an agonist response in the response of a ligand that is a non-competitive antagonist?

• irreversible

• can’t overcome antagonist effects regardless of how much increase in agonist conc.

• Emax is REDUCED

  • unable to shift to active receptors

What does it mean for a drug to be selective?

• drug has relative affinity for its target vs some other protein

• if a drug binds to other proteins in body other than target → non-selective

How does a selective drug differ from a specific drug?

• specific drug ONLY binds to a specific target

  • NO affinity for anything else

Why is poor selectivity a problem?

• if drug conc is increased and take up 99% of therapeutic target, it will also take up a similar amount of other proteins

  • will cause responses from unwanted targets

What is the ED50 for the therapeutic effect?

1 mg

1. find E max

2. Half the E max

3. find where the dose lines up

What is the ED50 for adverse effect?

40 mg

What is the LD50 for lethality?

400 mg

What is the therapeutic index? How is it calculated?

• safety of a drug

• LD₅₀/ED₅₀

What is the therapeutic index of agonist D?

TI = 400 mg/ 1 mg

TI = 400

What is the TI of agonist E?

TI = 2000 mg/ 1 mg

TI = 2000

What is the equation for TI in humans?

TI = ED₅₀ (adverse effect) / ED₅₀ (thera effect)

Which of these is due to poor selectivity of a drug?

a. a mechanism based adverse effect

b. an off target adverse effect

c. a therapeutic effect

d. a toxic effect

B

The effect of a competitive antagonist will shift the ED₅₀ of an agonist to the ____, making the agonist appear to be ___ potent.

a. left, more

b. right, less

c. left, less

c. right, more

B

T/F: ED50 is half of the maximal effect in a graded response but in a quantal response ED50 is the dose that produces the desired response in half the population.

TRUE

What is the effect observed when two active drugs are used in synergy?

a. A potentiated effect

b. The effect of one drug cancels out the effect of the other

c. A larger effect when compared to an additive effect

d. No difference in drug effects

C