Elimination

Describe the mechanisms of drug clearance and metabolism.

Drugs can be eliminated in:

  • Urine
  • Bile
  • Sweat
  • Breast milk
  • Tears
  • Exhaled gas

Renal Elimination

Drugs can be:

  • Filtered at the glomerulus
    Filtered drugs are:
    • Not protein bound
      Only free drug present in filtered plasma will be excreted.
      • Concentration of filtered drug will be the same as in unfiltered plasma
      • Highly protein bound drugs are poorly filtered
        There is only a weak concentration gradient favouring dissociation from plasma proteins.
    • Small
      • Substances less than 7,000 Da are freely filtered
      • Substances greater than 70,000 Da are essentially impermeable
    • Hydrophilic/lipophobic
      Lipophilic drugs may be filtered at the glomerus but will be freely reabsorbed during their passage down the tubule, such that only trivial amounts are eliminated in urine.
  • Secreted in the tubules
    • Active process allows secretion against concentration gradients
    • Separate mechanisms for acidic and alkaline drugs
      • Saturtable process
        Saturation may occur of a basic transporter whilst still allowing excretion of acidic drugs, and vice versa.
  • Reabsorbed in the tubules
    Passive diffusion down a concentration gradient.
    • Hydrophilic molecules can only be reabsorbed by a specialised transport mechanism
      • Acidic drugs will be become ionised in an alkaline urine (and vice versa), reducing their solubility
        This is the physiological justification for urinary alkalinisation.

Hepatic Elimination

Biliary elimination occurs for drugs unable to be filtered by the glomerulus. These are typically:

  • Large
    Greater than 30,000 dalton.
  • Lipid soluble

Enterohepatic recirculation

Drugs excreted in bile may:

  • Be hydrolysed in the small bowel by bacteria and then reabsorbed
  • Then pass through the portal circulation and get metabolised again
  • This process may occur many times

References

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
Last updated 2017-09-16

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