16A08: Exam Report

Describe the characteristics of a drug that influence its excretion by the kidneys.

29% of candidates passed this question.

Drug characteristics that might influence the renal excretion processes include charge, size, solubility, and binding to specific structures or protein. Whether the drug is unchanged versus metabolised can influence these factors.

This question tests core knowledge of pharmacology principles and should be answered with equations, graphs or simple clear descriptions of physical and chemical principles. Extended examples and hedged statements about “influencing” without the direction, magnitude and necessary conditions for the influence did not score marks.

Biv / 16A08: Describe the characteristics of a drug that influence its excretion by the kidneys

Most drugs (or their metabolites) are excreted by the kidneys

3 processes occur during renal excretion

  • Glomerular Filtration
  • Tubular Secretion
  • Passive Reabsorption

Glomerular Filtration – a passive process that removes small molecules and is influenced by

  • Renal Blood flow – autoregulated, however changes in RBF will alter the rate of drug excretion through its influence on GFR
  • Charge
    • Cationic substances filtered more readily compared to anionic substances → due to negatively charged glycoproteins in filtration barrier
    • In terms of increasing filterability: negative << neutral << positive charge
  • Size
    • Particles < 7 kDa are filtered freely, between 7-70 kDa are ↓ freely filtered, and > 70 kDaare not filtered;
    • neutral particles < 4 mm diameter filtered freely, between 4-8 mm are partly filtered, and > 8 mm are excluded
  • Solubility
    • Lipophilic drug more likely to be filtered, but also likely to be reabsorbed
  • % unbound to protein
    • free drug is freely excreted
    • drug that is protein bound is poorly filtered
  • Whether drug is unchanged vs metabolized – primary site of biotransformation is liver (although some drugs are metabolised in renal tubules ie 30% of insulin) and will affect the size/charge/solubility and PPB of the drug

Proximal Tubular Secretion – an active process

  • Drugs (esp organic acids) are actively secreted into renal tubules against their [ ] gradients
  • Different carrier systems exist for acidic and basic drugs→each are capacity-limited for their respective drug type (Ie. max. clearance of one acidic drug is limited by clearance of another, but not by basic drug)

Passive Tubular Reabsorption

  • Lipid-soluble fraction of drugs in the distal tubules are reabsorbed via passive diffusion → prevented from excretion in urine
  • Rate of reabsorption depends on pH of Ultrafiltrate
    • Determines the degree of ionization of a drug – exploited by altering urine pH to influence the rate of excretion of acidic/basic drugs by ion trapping thereby reducing passive resorption

Author: Huiling Tan