Final answer:
Local anesthetics' potency, duration, and onset are determined by the pH of the tissue, lipid solubility, protein binding, and ionization constant. These properties influence how anesthetics interact with nerve tissue and cells, affecting their anesthetic and pharmacokinetic profiles.
Step-by-step explanation:
The determinants of potency, duration, and onset of local anesthetics include: pH of the tissue, lipid solubility, protein binding, and ionization constant. The pH of the tissue can affect the ionization state of the anesthetic, thereby altering its solubility and ultimately the onset and duration of action. Lipid solubility is important because anesthetics must penetrate lipid membranes to reach their site of action; more lipid-soluble compounds typically have greater potency and longer duration. Protein binding affects both the duration of action and the drug's reservoir within the body, with higher binding leading to prolonged effects. Lastly, the ionization constant (pKa) relates to the proportion of the drug that is ionized versus non-ionized, influencing the drug's ability to cross cell membranes and therefore its onset of action.