Drug action at receptors

• What are the three terms students should be able to define after the lecture?

  Specificity, affinity, and efficacy
• What are receptors primarily composed of?


  Protein macromolecules
• What are the two main functions of receptors?


  Recognition of extracellular molecules and transduction of signals
• How do receptors interact with chemicals?


  With a high degree of specificity
• What is an example of a receptor named after a drug?

  Nicotinic acetylcholine receptors
• How do pharmacologists utilize receptor specificity?


  By designing drugs that bind to certain subtypes of receptors
• What is the significance of drugs being highly selective in their action?


  They lead to drugs with fewer side effects
• How is the binding of drug (D) to receptor (R) characterized?


  Binding is reversible in most cases
• What shape does the plot of the proportion of receptors occupied (p) vs drug concentration [D] take?


  A rectangular hyperbola
• What shape does the plot of the proportion of receptors occupied (p) vs log [D] take?


  A symmetrical sigmoid
• What does the symbol K_D represent?


  The molar concentration of drug required to occupy 50% of the receptors at equilibrium
• How do drugs with high affinity relate to K_D?


  They have a low K_D
• What are the rate constants k₊₁ and k_-1 used for?


  To describe the likelihood of the forward and backward reactions occurring
• What is the relationship at equilibrium between the forward and backward reactions?


  Backward rate equals forward rate
• What does K_D measure?


  How tightly the receptor holds on to the drug
• What happens to receptors when they are bombarded by many chemicals?


  Only those with affinity will bind
• What is the difference between agonists and other drugs?


  Agonists bind and activate the receptor
• What is efficacy in relation to agonists?


  The ability of a drug to activate the receptor
• What does activation of receptor (R) by an agonist (A) produce?


  A biological response
• How long is the human β2 adrenoceptor?


  About 400 amino acids long
• What is remarkable about the hormone adrenaline in relation to the β2 adrenoceptor?


  It is the size of a single amino acid
• What are the two broad types of agonists?


  Partial agonists and full agonists
• What do full agonists do?


  They have high efficacy and activate receptors effectively
• What do partial agonists do?


  They have low efficacy and are less effective at activating receptors
• What is a characteristic of full agonists in terms of receptor activation?


  They can produce a maximal response while activating only a fraction of the available receptors
• What is a characteristic of partial agonists in terms of receptor activation?


  They often fail to produce a full response despite occupying all available receptors
• How do the log concentration vs response curves differ between full and partial agonists?


  Full agonists produce a higher response than partial agonists
• Why is it misleading to conclude that an agonist will produce a 50% response when occupying 50% of the receptors?


  Because the overall response is determined by both affinity and efficacy
• What is the relationship between EC₅₀ and K_D?


  EC₅₀ is not the same as K_D due to multiple steps between binding and response
• What do we call drugs that show both affinity and efficacy at receptors?

  Agonists
• What is the difference between affinity and efficacy?


  Affinity refers to binding, while efficacy refers to activation of the receptor
• What do we call drugs that have low efficacy?

  Partial agonists
• Is the EC₅₀ for an agonist drug always the same as its K_D?


  No, because of the differences in affinity and efficacy
• What do antagonists do?


  They inhibit the effects of neurotransmitters or hormones
• What are the distinct forms of antagonism?


  Chemical, pharmacokinetic, and physiological antagonism
• What is chemical antagonism?


  Using one drug to chemically inactivate another
• What is pharmacokinetic antagonism?


  One drug alters the way the body deals with another
• What is physiological antagonism?


  Two drugs act to produce opposing effects
• What do competitive antagonists do?


  They compete with the agonist for the same site on the receptor
• What is the efficacy of competitive antagonists?


  They have affinity but zero efficacy