Pharmacodynamics

• Negative modulator: Binds to the allosteric site of a receptor to decrease effects of the agonist
• Positive modulator: Binds to the allosteric site of a receptor to increase effects of the agonist
• Attenuating: Reducing the effect
• Pharmacodynamics: Studies of the biochemical and physiological effects of drugs
• Metabolism + excretion = elimination
• Pharmacodynamics has an emphasis on the dose-response relationship
• Dose-response relationship


  Relationship between drug concentration and drug effect
• Pharmacologists use the generic drug name
• Product information sheets are available to health professionals
• Consumer Medicine Information (CMI) is written for the public
• Drugs can be classified by:

  Chemical structure, mechanism of action, therapeutic use
• Affinity refers to a drug's ability to bind to the target
• How is affinity quantified?

  the concentration of drug required to occupy 50% of target proteins
• Drugs with high affinity only need a very small concentration to bind to the target
• Selectivity refers to the ability of a given drug concentration to produce one effect over another
• Side effects occur because no drug is entirely specific to one target
• Off-target side effects: the drug binds to the wrong target
• On-target side effects: the drug binds to the correct target but produces unwanted physiological effects
• Selectivity is concentration dependent
• Increase in concentration = increased probability to bind to lower affinity targets
• Intrinsic efficacy is a measure of the ability of a drug to elicit a response
• How is intrinsic efficacy measured?

  Comparing the maximal effect of the drug to the maximal effect of a full agonist on the same tissue
• Full agonist: Intrinsic efficacy = 1
• Full antagonist: Intrinsic efficacy = 1
• Partial antagonist: Intrinsic efficacy between 0 and 1
• Intrinsic efficacy may account for:

  • Receptors being in different activation states
  • Binding of only some receptors giving a maximum response
• Potency refers to the concentration of a drug that produces a specified effect
• High potency is important to ensure that a pill is small enough to swallow
• Higher potency = produces effect at a smaller quantity
• A receptor is a macromolecular complex which binds to a ligand with high selectivity which produces a characteristic effect as a consequence
• The ligand is very small compared to the receptor
• Four types of receptors:

  1. Metabotropic
  2. Ionotropic
  3. Kinase-linked receptors
  4. Nuclear receptors
• G-protein coupled receptors = metabotropic
• Ligand-gated ion channels = ionotropic
• Ligand: A molecule that binds to an active site on a macromolecule (target)
• What are the three stages of drug action?

  Binding, conformational change and transduction, and response
• Once a drug has bound, the effect can be:

  Activating, Enhancing, Attenuating, Interfering
• What has an activating effect?

  Agonists
• What has an enhancing effect?

  Positive modulators
• What has an attenuating effect?

  Negative modulators