Drug Disposition: Excretion

Question 1

(1) Why is the kidney important in excretion?

Answer 1

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)

Question 2

(1) Why is the liver important in excretion?

Answer 2

liver plays an important role in solubulization of xenobiotics

Question 3

(2) Describe the physiology of the renal tubule that is essential for transport of drugs into urine.

Answer 3

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

Question 4

(2) The amount of drug entering the tubule lump depends on which two variables?

Answer 4

amount of drug entering tubule lumen depends on GFR and extent of binding to large proteins

Question 5

(3) Describe the 3 mechanism of renal excretion

Answer 5

1. tubular transport: endocytosis is important for proteins and polypeptides that are filtered in the proximal tubule
2. passive reabsorption and active secretion are the most important process for drugs; only lipophilic molecules and affected by pH
3. 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

Question 6

(4) How does the pH of urine effect the excretion of drugs?

Answer 6

if urine is more acidic, increase in exc of weak bases; if urine is more basic, increase in excretion of weak acids

Question 7

(5) What equation does this course use to estimate renal function.

Answer 7

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

Question 8

(6) Explain the process of biliary excretion.

Answer 8

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)