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Drug Elimination

Drug Elimination. Drug Elimination. Biotransformation Hepatic, Renal, Pulmonary Secretion of unchanged drug Renal, biliary (hepatic), GI, mammary, salivary…. Metabolism vs excretion. Liver can do two things to drug molecules and each of them has subtypes 1)      Metabolism

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Drug Elimination

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  1. Drug Elimination

  2. Drug Elimination • Biotransformation • Hepatic, Renal, Pulmonary • Secretion of unchanged drug • Renal, biliary (hepatic), GI, mammary, salivary…

  3. Metabolism vs excretion • Liver can do two things to drug molecules and each of them has subtypes • 1)      Metabolism • a.       Liver may just change the drug’s structure (metabolism) • b.      Liver may conjugate a drug with something else (metabolism) • 2)      Secretion (not metabolism) • a.       Liver may just put a drug molecule in bile without changing it • b.      Liver may grab a conjugate (that it made in 1b) and secrete the conjugate in bile • 1b is metabolism, 2b is not.  Dr. Ehrich will also tell you that sometimes it’s 1a -> 1b -> 2b (if the drug molecule has to be prepared before conjugation can occur).

  4. Metabolism vs Excretion • Kidney • 1)      99% of what the kidney does to drugs is just secretion/excretion.   • Glomerular filtration does not change the drug structure so it is not metabolism.  Same for tubular secretion. • 2)      TECHNICALLY, the kidney also has the ability to metabolize small molecules.  • Mostly amino acids and things that look like amino acids.  This metabolic ability is rarely important but it exists for some drugs.

  5. 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.

  6. Biotransformation • Chemical mechanisms • Oxidation • Hydroxylation • Hydrolysis • Reduction • Conjugation • Acetylation • Glucuronidation • Sulfation • …

  7. Hepatic metabolism

  8. 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

  9. Renal excretion • Renal elimination • Glomerular filtration + • Tubular secretion) – • Passive reabsorption

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

  11. 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.

  12. 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.

  13. Pulmonary elimination • Metabolism • Autocoids • Exhaled gases • Volatile compounds

  14. 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.

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