VM 8314
Dr. Wilcke

VM 8314
 Biotransformation
 Hepatic, Renal, Pulmonary
 Secretion of unchanged drug
 Renal, biliary (hepatic), GI, mammary, salivary…
Dr. Wilcke

VM 8314
 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).
Dr. Wilcke

VM 8314
 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.
Dr. Wilcke

VM 8314
 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.
Dr. Wilcke

VM 8314
 Chemical mechanisms
 Oxidation
 Hydroxylation
 Hydrolysis
 Reduction
 Conjugation
 Acetylation
 Glucuronidation
 Sulfation
 …
Dr. Wilcke

VM 8314
Dr. Wilcke

VM 8314
 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
Dr. Wilcke

VM 8314
 Renal elimination
 Glomerular filtration +
 Tubular secretion) –
 Passive reabsorption
Dr. Wilcke

VM 8314
 Nephron animation
 Animation shows glomerular filtration and passive reabsorption, it does NOT demonstrate tubular secretion.
Dr. Wilcke

VM 8314
 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.
Dr. Wilcke

VM 8314
 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.
Dr. Wilcke

VM 8314
 Metabolism
 Autocoids
 Exhaled gases
 Volatile compounds
Dr. Wilcke

VM 8314
 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.
Dr. Wilcke