Drug Disposition: Excretion Flashcards
(1) Why is the kidney important in excretion?
renal system has 3 ways to cause excretion of drugs: glomerular filtration, passive tubular reabsorption and active tubular secretion; renal system sees entire blood volume for filtration (10% of renal arterial blood supply gets filtered)
(1) Why is the liver important in excretion?
liver plays an important role in solubulization of xenobiotics
(2) Describe the physiology of the renal tubule that is essential for transport of drugs into urine.
all drugs of low MW will end up in the filtrate through glomerular filtration; passive reabsorption in the tubules of water will lead to the passive reabsorption of drugs if they are lipophilic
(2) The amount of drug entering the tubule lump depends on which two variables?
amount of drug entering tubule lumen depends on GFR and extent of binding to large proteins
(3) Describe the 3 mechanism of renal excretion
- tubular transport: endocytosis is important for proteins and polypeptides that are filtered in the proximal tubule
- passive reabsorption and active secretion are the most important process for drugs; only lipophilic molecules and affected by pH
- active secretion: active transport from plasma to urine, as in ATP-binding cassette transporters; organic anion and cation secretion proteins (these transporters alter the blood equilibrium of bound and unbound proteins) by OATs and OCTs
(4) How does the pH of urine effect the excretion of drugs?
if urine is more acidic, increase in exc of weak bases; if urine is more basic, increase in excretion of weak acids
(5) What equation does this course use to estimate renal function.
the Cockcroft-Gault equation; is a calculation to determine the creatinine clearance (normal 97-137 mL/min; 88-128mL/min)
which important for understanding how to adult dosing for those with impaired renal function
(6) Explain the process of biliary excretion.
molecules of a minimum molecular weight are conducted to increase MW above threshold for active transport from the plasma to the billiard canal; can include ATP-binding cassette transporters (broad specificity)