Pharm Midterm

• Pharmacodynamics


  Biochemical, cellular, and physiological effects of drugs and their mechanisms of action
• Receptor


  Cellular macromolecule with which the drug interacts to elicit an effector
• Effector


  Mechanism activated by receptor
• Signaling molecule such as epinephrine
• Receptor Interactions


  1. First messenger binds to cell-surface receptor

  2. Effector occurs = mechanism activated by receptor

  3. Second messengers, or small intracellular signaling molecules, can carry out additional cellular responses by binding to cytosolic or nuclear receptors
• Communication between cells depends on signaling molecules
• Signaling molecules can be produced in one cell, and used to transmit a message to one (or many) other cells
• Signaling molecules can include exogenous compounds, such as medications, or endogenous compounds, such as neurotransmitters
• Signaling molecules bind to a receptor that is a specific protein that is a site of binding of that particular signaling molecule
• Messenger system


  1. Receptors can be located on the outside of the cell or within the cell

  2. The signaling molecule that binds to the extracellular receptor is the first messenger, i.e. epinephrine

  3. The signaling molecule that activates proteins within the cell is the second messenger, i.e. cAMP
• Ligands


  All messengers are compounds that bind to a receptor
• Agonists


  Ligands that bind to receptors and activate effector
• Full agonist


  Fully activates receptor, i.e. elicits MAXIMAL effect
• Partial agonist


  Partially activates receptor, i.e. elicits small effect
• Antagonists


  Ligands that bind to receptors, but do not activate effector
• Competitive antagonist


  Competes with an agonist for binding site, i.e. blocks agonists
• Noncompetitive antagonist


  Binds to receptor at a different site, and effectively reduces the maximal response of an agonist
• Cytosolic or nuclear receptors are ligand-activated gene regulatory proteins
• When bound by signaling molecules, cytosolic or nuclear receptors bind to DNA and regulate transcription of specific genes
• Spare receptors


  Receptors that exist beyond what is required to have a full response
• ED50


  Effective dose for 50%
• TD50


  Toxic dose for 50%
• LD50


  Lethal dose for 50%
• Therapeutic window


  Dosage range between the minimum effective therapeutic concentration and the minimum toxic concentrations
• Theophylline example: Minimum [therapeutic]: 8 mg/L, Minimum [toxic]: 18 mg/L, Therapeutic window: 8-18 mg/L
• Receptor desensitization


  As cells are repeatedly stimulated, feedback mechanisms can result in diminished effects of the agonist
• Pharmacokinetics


  How the body affects the drug (LADME)
• Pharmacodynamics


  How the drug affects the body
• Liberation


  Drug form
• Absorption


  Rate and extent is dependent upon route of administration
• Bioavailability


  Fractional extent to which an administered dose of drug reaches its site of action or a biological fluid (usually the systemic circulation) from which the drug has access to its site of action
• First-pass metabolism


  Occurs for oral drugs that must be absorbed from GI tract, then enter the liver before reaching systemic circulation
• Tablet types


  • Enteric coated
  • Sustained release (timed release)
  • Chewable
  • Sublingual
• Oral liquids


  Easy to swallow and possibly work more rapidly than tablets or capsules, as the drug is already "liberated"
• Oral liquid types


  • Suspensions
  • Solutions
  • Syrups
  • Elixirs
  • Tinctures
  • Emulsions
• Sublingual and buccal


  Medications administered in this manner bypass the digestive system, and are absorbed directly into the bloodstream
• Topical agents


  Can have systemic or local effects
• Topical agents


  • Testosterone (systemic)
  • Diclofenac (NSAID), lidocaine patch, hydrocortisone (local)
• Ointments


  Semisolid preparations containing petroleum or another base
• Creams


  Semisolid emulsions applied directly onto the skin