Pharmacodynamics

Question 1

Define steroisomerism as it pertains to drugs.

Answer 1

• drugs w/ asymmetric carbon atoms exist in more than one enantiomeric form
• chirality: usually only one enantiomer can interact w/ receptor (active enantiomer)

Question 2

What factors influence ligand (drug) binding to receptors?

Answer 2

• K_{<strong>D</strong>}= dissociation constant for a drug-receptor interaction
  
  • at Equilibrium
    
    • [D] [R]/ [RD] = K_off / K_on = K_D
• 1/ K_D = affinity of drug for receptor
• B_max = maximum bindng of drug to receptors

Question 3

What are spare receptors?

Answer 3

• present when the maximum drug effect does not require 100% of receptors to be occupied by drug
• number of activated receptors is not the limiting factor for drug action
• dose-response curve shifted to left relative to concentration-binding curve

Question 4

Define agonist.

Answer 4

• drug that binds or stabilizes the active conformations of the receptor –> initiates a response

Question 5

Define partial agonist.

Answer 5

• drug that promotes a response less than the maximum caused by full agonist at full receptor occupancy
• when spare receptors are present, partial agonist can produce a full agonist response

Question 6

Define antagonist.

Answer 6

produce no effect on their own, but block effects of agonists

Question 7

Define inverse agonist.

Answer 7

• produce effects opposite to those produced by agonist at same recepor
• only ovserved in systems with constitutive activity (i.e. where receptor is always active in the absence of a regulatory ligand)

Question 8

How is agonism quantified?

Answer 8

potency & efficacy

Question 9

Define efficacy. What is the relative efficacy of the different drug types?

Answer 9

• magnitude of the maximym response induced by an agonist (to stabilize the active form of the receptor)
• along y-axis of dose-response curve
• **different from clinical efficacy: maximum therapeutic benefit regardless of mechanism**

Question 10

Define potency.

Answer 10

• dose or concentration needed to cause a defined level of response
• along x-axis of dose-response curve, right shift = less potent

Question 11

What are the types of antagonists?

Answer 11

• non-receptor
  
  • **chemical antagonist **
  • physiological antagonist
• receptor
  
  • active site binding
    
    • reversible: competitive antagonist
    • irreversible: noncompetitive active site binding antagonist
  • allosteric binding
    
    • reversible noncompetitive allosteric antagonist
    • irreversible noncompetitive allosteric antagonist

Question 12

What are the types of antagonism?

Answer 12

• competitive antagonist
• non-competitive antagonist
  
  • irreversible antagonist
  • allosteric ligand
• chemical antagonism
• physiologic antagonism

Question 13

Define competitive antagonists and their characteristics.

Answer 13

• binds reversibly to same site on receptor as agonist
• increases concentration of agonist (x-axis) needed to give 50% maximum effect (EC₅₀)
• decrease potency, same maximal effect–> shift curve to the right

Question 14

Define irreversible antagonists and their characteristics.

Answer 14

• react covalently with agonist binding site of receptor, cannot be competed by high concentrations of agonist
• reduces maximum response by agonist (efficacy) –> decreases efficacy w/ minimal rightward shift in agonist EC₅₀

Question 15

Define allosteric ligands and their characteristics.

Answer 15

• reversible or irreversible non-competitive antagonist that can bind to a different allosteric site on receptor and reduce the affinity of agonist for agonist site
• can antagonize (reduce efficacy) or potentiate (increase potency) effects of agonist

Question 16

Define chemical antagonism.

Answer 16

one drug complexes with another in solution- no receptor interaction occurs

Question 17

Define physiologic antagonism.

Answer 17

two different drugs activating two mutually antagonistic regulatory pathways thru different receptors reduce the effect of each agent given alone

Question 18

What is desensitization?

Answer 18

reduction of response to agonist due to repeated exposure to an agonist

Question 19

What is homologous desensitization?

Answer 19

• specific receptor being acted on by specific agonist becomes rapidly desensitized
• receptors are rendered ineffective quickly
• other signaling pathways that use different receptors but same pathway can still effect biological effect

Question 20

What is heterologous desensitization?

Answer 20

• loss of responsiveness to agonists acting at several receptor types
• agonist-induced signal transduction cascade results in inactivation of other receptor types in vicinity

Question 21

What is down-regulation?

Answer 21

reduced rate of receptor synthesis or increased degradation