ADME 5:Drug excretion

Question 1

What is drug excretion?

Answer 1

Excretion is the process whereby compounds are removed from the body to the external environment.

Question 2

What are the sites of drug excretion?

Answer 2

-Kidney(most important)
-Biliary excretion( drugs with MW>400 and ionised) eg Glucoronide
Lungs (anaesthetic gases)

Question 3

What is the most important function of the kidney?

Answer 3

It removes H2O soluble drugs and metabolites.

Question 4

How much urine do we produce/day and how much of it ends up being excreted?

Answer 4

We produce 190L/day of urine. But 99% of this is reabsorbed so we end up with 1.9 L of urine/day.

Question 5

What are the 3 mechanisms for drug excretion by the kidney?

Answer 5

1. Glomerular filtration
2. Active secretion
3. Passive reabsorption.

Question 6

What happens at the glomerulus filtration?

Answer 6

Filter 20% of the plasma or 10% of the renal blood flow.

• Only the unbound drugs are filtered ie the 20% plasma that is filtered consists only of unbound drugs.
• Lare proteins are not filtered.

Question 7

What happens during active secretion?

Answer 7

Moving drug from the filtrate into urine. This occurs through Glucuoronide. They carry the metabolites/drugs from blood and take them into the urine.
-Glucuoronides have high affinity for the drug so they can remove drugs bound to the proteins as well.

Question 8

What happens during passive reabsorption?

Answer 8

High concentration of drug in the tubules. So any drug that is lipid soluble will go back from the tubule(urine) into the bloodstream.

Question 9

What prevents passive reabsorption of a drug?

Answer 9

If the drug becomes ionised for example due to a weak acid in the alkaline urine environment.

Question 10

What are the factors influencing renal drug excretion?

Answer 10

• Gender- males have a better renal function than females
• Renal function decreases with aging
• Renal function increases in pregnancy
• Renal function is affected by renal disease, heart failure

Question 11

What substance is used as an index of renal function?

Answer 11

Creatine

Question 12

What are the factors which alter renal excretion of drugs?

Answer 12

1. Competitive inhibition of tubular secretion eg reduced excretion by using probenecid
2. Influence of pH eg sodium bicarbonate alkalises urine which rapidly ionises weak acids. Therefore ionised substances are not reabsorbed= facilitates excretion
   Similarly ammonium chloride acidifies urine to enhance excretion of basic drugs eg amphetamines
   3.Influence of urinary flow rate-increased flow rate=dilutes concentration of drug in tubule=decreased reabsorption=enhanced excretion.
   Similarly decreased flow rate=increased drug conc in tubule=passive reabsorption=decreased excretion