1 excretion Flashcards
what is the outline of excretion?
-renal excretion (kidneys)
-biliary excretion (liver and fecal)
-pulmonary excretion (lungs)
-other routes of excretion
renal excretion is the most important xenobiotic ___________ in vertebrate animals
ELIMINATION PATHWAY
what are the 3 processes involved in changing blood level (clearance) of a xenobiotic?
-glomerular filtration
-tubular reabsorption
-tubular secretion
what is the graph of tubular secretion in kidney tubules?
kidneys filter about 180L a day (filter plasma 60 times a day)
-facilitated diffusion transporters (OATs and OCTs)
-active transporters (BCRP, MRP, MDR) to move against conc gradient, pump to more conc area
-both have certain affinities for certain xenobiotics that can differ from eachother
what is extrarenal excretion?
- biliary excretion
- pulmonary excretion
- lactation
- minor routes of excretion
what is biliary excretion?
-important for “larger” xeno molecules (MW >300g/mol)
-similar to kidney, facilitated transport (OAT AND OCT) and active transport (MDR, MRP, BCRP) proteins are involved
-hepatocyte=liver cells
-hepatocyte makes xenobiotic (not all) become more water soluble (phase 1 and phase 2 occurs)
what are the options of what xenos can do in hepatocyte?
-can never even make it to liver and get excreted into feces
-can be bioactivated by something in the hepatocyte and become much more toxic
-can be metabolized and detoxified in the hepatocyte and pumped in biliary duct and excreted
what is enterohepatic cycling?
-xenos or xeno metabolites excreted in the bile into the intestine can be reabsorbed and distributed back to the liver (why its called cycling)
-this can increase the half-life of a xeno, and in the case of xenos producing toxic metabolites, exacerbate toxicity to the liver
what is pulmonary excretion (exhalation)?
-important for volatile and gaseous xenos (ammonia gas)
-ex: ethanol is 90% metabolized in liver but approximately 2% is excreted in the expired air; basis for breathalyzer test
what is lactation?
-can be a significant route of elimination for lipophilic xenos, ranging from 0.1 to 2% of maternal dose
-important consideration for neonatal exposure
-important consideration for food products (ex: milk and cheese)
what are the minor routes of excretion?
-saliva
-sweat
-hair and nails
what is the spiderweb of linking ADME to toxic effects?
what are xenobiotic interactions?
-the coadministration of two or more xenos is often associated with altered excretion of one (or more) of the xenos
what are some important terms of xenobiotic interactions?
-summation (additivity)
-synergism
-potentiation
-antagonism
what is summation (additivity)?
-theoretical example: if the effect of xeno A is 2 and the effect of xeno B is 2, then coadministration of both xenos produces a combined (additive) effect of 2+2=4 (ie: there is no interaction and the effects are additive)
-this is most common, but there are exceptions
