Drug Elimination
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VM 8314 Dr. Wilcke Drug Elimination Drug Elimination
description
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 - PowerPoint PPT Presentation
Transcript of Drug Elimination
VM 8314
Dr. Wilcke
Drug EliminationDrug Elimination
VM 8314
Dr. Wilcke
BiotransformationHepatic, Renal, Pulmonary
Secretion of unchanged drugRenal, biliary (hepatic), GI, mammary,
salivary…
Drug EliminationDrug Elimination
VM 8314
Dr. Wilcke
Metabolism vs excretionMetabolism 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 bile1b 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).
VM 8314
Dr. Wilcke
Metabolism vs ExcretionMetabolism vs ExcretionKidney
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.
VM 8314
Dr. Wilcke
BiotransformationBiotransformationConversion 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 drugBecause other ways out of the body are
inaccessible.
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BiotransformationBiotransformationChemical mechanisms
OxidationHydroxylationHydrolysisReductionConjugation
AcetylationGlucuronidationSulfation…
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Dr. Wilcke
Hepatic metabolismHepatic metabolism
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Biliary excretionBiliary excretionActive secretion
High molecular weight drugsMOSTLY conjugates (drugs
themselves rarely are big enough for the mechanism to work)
Passive secretionLow molecular weight drugsBiliary concentrations = plasma water
concentrations
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Renal excretionRenal excretionRenal
eliminationGlomerular
filtration +Tubular
secretion) – Passive
reabsorption
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Renal excretionRenal excretionNephron animation
Animation shows glomerular filtration and passive reabsorption, it does NOT demonstrate tubular secretion.
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Dr. Wilcke
Renal excretionRenal excretionPassive reabsorption can be reduced
DiseaseTherapeutic intervention
Decreasing passive reabsorption increases elimination rateDrug overdosesPoisonings
Passive reabsorption cannot be manipulated if it is not occuring.
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Dr. Wilcke
Renal excretionRenal excretionFor 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.
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Pulmonary eliminationPulmonary eliminationMetabolism
AutocoidsExhaled gases
Volatile compounds
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Dr. Wilcke
Pulmonary metabolismPulmonary metabolismAutocoids are often metabolized
in the lungLung is the only organ that
receives 100% of the cardiac output
Therefore, pulmonary metabolism of drugs will produce an EXTREMELY short duration of effect.
