Drug Actions

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  • The most important & common mechanism by which drugs exert pharmacologic effects is by interaction of the drug with a specific protein molecule in the lipid bilayer of cell membranes - a receptor
  • Similar receptors exist for endogenous regulatory substances eg. hormones and neurotransmitters
  • A drug-receptor interaction alters the function or conformation of a cellular component, initiating a series of changes that bring about the pharmacologic effects of the drug
  • Can also work via intracellular receptors, or by stimulating or inhibiting enzyme systems
  • Steroid hormones are lipophilic, crossing lipid layers and interacting with steroid receptors in the cytoplasm
  • The steroid hormone-receptor complex acts as a transcription factor - binds to regulatory DNA sequences in target genes and alters their transcription
  • Physico-chemical Interactions - drugs can also work by forming strong bonds with metallic cations (chelating drugs) and direct neutralization of gastric acid (antacids)

Drug-Receptor Interaction

  • Agonists - drug-receptor interaction elicits a pharmacological effect by altering the functional properties of the receptors
  • Antagonist - interacts with receptors but does not alter their functional properties, and prevents their response to an agonist at the same time
  • Competitive antagonist - antagonist inhibition can be overcome by increasing the concentration of agonist - eg. NMJ blocking drugs and beta blockers
  • Non-competitive antagonist - antagonist inhibition which is irreversible, and reduce the maximum response possible by increasing agonist concentration
  • Partial agonist - binds only weakly to receptors and produces only a minimal pharmacologic effect, even at maximal concentration
  • Receptor Occupancy Theory - assumption that intensity of effect produced by binding of drugs to receptors is proportional to the fraction of receptors occupied by the drug
  • Does not explain the differences in intrinsic activity between drugs occupying the same number of receptors
  • State of Receptor Activation - partial agonists convert only a fraction of the receptors they occupy to the activated state
  • Increasing doses of a partial agonist in the presence of maximal effect results in competitive antagoism of the effect of the agonist
  • Multiple bond types occur between drugs and complementary regions of receptors
  • Covalent bonding - involved in inactivation of cholinesterase enzyme by organophosphates
  • Ionic bonding - arise from electrostatic forces between groups of opposite charge - especially acidic/basic drugs
  • Hydrogen bonding - between hydroxyl/amino groups
  • Van der Waals forces - weak bonds between two atoms