Drug Elimination

1

• Drug Elimination

2
Drug Elimination

• Biotransformation
• Hepatic, Renal, Pulmonary
• Secretion of unchanged drug
• Renal, biliary (hepatic), GI, mammary, salivary

3
Biotransformation

• Conversion of drug to metabolite
• Inactivates drug or
• Reduces drug activity or
• Activates drug (would not be elimination)
• Major route of elimination for lipid soluble and
  protein bound drug
• Because other ways out of the body are
  inaccessible.

4
Biotransformation

• Chemical mechanisms
• Oxidation
• Hydroxylation
• Hydrolysis
• Reduction
• Conjugation
• Acetylation
• Glucuronidation
• Sulfation

5
Hepatic metabolism
6
Biliary excretion

• Active secretion
• High molecular weight drugs
• MOSTLY conjugates (drugs themselves rarely are
  big enough for the mechanism to work)
• Passive secretion
• Low molecular weight drugs
• Biliary concentrations plasma water
  concentrations

7
Renal excretion

• Renal elimination
• Glomerular filtration
• Tubular secretion)
• Passive reabsorption

8
Renal excretion

• Nephron animation
• Animation shows glomerular filtration and passive
  reabsorption, it does NOT demonstrate tubular
  secretion.

9
Renal excretion

• Passive reabsorption can be reduced
• Disease
• Therapeutic intervention
• Decreasing passive reabsorption increases
  elimination rate
• Drug overdoses
• Poisonings
• Passive reabsorption cannot be manipulated if it
  is not occuring.

10
Renal excretion

• For most drugs and most poisons, increasing urine
  output (by giving fluids or diuretics) will NOT
  increase the elimination rate of the drug.
• Increasing urine output will however, decrease
  the concentration of the drug or poison in the
  renal tubule and may spare the kidney from damage.

11
Pulmonary elimination

• Metabolism
• Autocoids
• Exhaled gases
• Volatile compounds

12
Pulmonary metabolism

• Autocoids are often metabolized in the lung
• Lung is the only organ that receives 100 of the
  cardiac output
• Therefore, pulmonary metabolism of drugs will
  produce an EXTREMELY short duration of effect.