ADME Four

Question 1

What are the sites of drug excretion?

Answer 1

• Kidney
• Biliary Excretion (MW>400 & Ionized drugs e.g Drug-glucuronide conjugates)
• Lungs

Question 2

What is the product of metabolism

Answer 2

metabolites

Question 3

What is the kidneys main homeostatic role?

Answer 3

Regulates blood volume and fluid composition

Question 4

IN relation to drugs what does the kidney do?

Answer 4

Removes water soluble drugs and metabolites ((excretion)) (depends on physico-chemico properties)

Question 5

Up to what MW is filtered by the kidney

Answer 5

30,000MW

Question 6

What is the average Glomerular filtration rate in an adult?

Answer 6

130mL per min

Question 7

What are the three steps of drug excretion by the kidney?

Answer 7

1) Filtration
2) Active secretion of free and protein bound drugs by transporters
3) Filtrate is concentrated in the Tubules for favorable reabsorption conditions

Question 8

What anions and cations are secreted into the tubules?

Answer 8

Anions- Glucuronide and sulphate conjugates

Cations- Histamine, basic drugs

Question 9

Are drugs bound to plasma proteins filtered?

Answer 9

No their MW is too high, thus only free plasma drugs filtered.

Question 10

What are some factors influencing renal excretion?

Answer 10

Gender (F have 0.8 function of males)
Age (50% decrease by 75)
Pregnancy (increased by 50%)
Disease (renal failure, heart failure- decreased blood to kidney

Question 11

How can renal excretion be changed with drugs?

Answer 11

Competitive inhibition of tubular secretion
Influence of urinary pH
Influence of urinary flow rate

Question 12

How does competitive inhibition of tubular secretion effect renal excretion of drugs?

Answer 12

Can prevent up to 90% of drug secretion (as at least 10% is always filtered

Question 13

How does influence of urinary pH effect renal excretion?

Answer 13

E.g Sodium bicarbonate is used to increase pH which increases ionization of weak acids and thus decreases tubular re-absorption = increase excretion

e.g Ammonium Cl used to increase tubular pH which increases excretion of basic drugs (e.g meth)

Question 14

How does urinary flow rate increase renal excretion?

Answer 14

(more water) increase urinary flow rate which decrease concentration of tubular fluids, decreasing the concentration gradient for passive reabsopriton of drug thus increased secretion.