Elimination and Excretion

Describe the mechanisms of drug clearance and metabolism.

Drug:

Elimination is the removal of drug from the plasma, and includes distribution and metabolism
Excretion is the removal of the drug from the body
Via:
- Urine
- Bile
- Sweat
- Breast milk
- Tears
- Exhaled gas

Renal Excretion

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 glomerulus 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
  - Saturatable 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.

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

Drugs excreted in bile may:

Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.

Last updated 2020-07-30