Drug Excretion And Factors Affecting This

Question 1

What are the routes of excretion?

Answer 1

Lungs, bile, urine, sweat and breast milk.

Question 2

How can routes of excretion be exploited in the treatment of drug overdose?

Answer 2

Some drugs pass straight through the GI tract.
For example in a drug overdose using charcoal (inert compound)

The drug is adsorbed irreversibly
A concentration gradient is maintained
The drug is continuously removed.

Charcoal is inert so it will be eliminated by the faeces.

Question 3

How is urine alkalinised for aspirin overdose excretion?

Answer 3

Increase in pH so aspirin stays ionised. It’s not reabsorbed by the kidneys so is passed out via the urine.

Question 4

How can net renal excretion be calculated?

Answer 4

Net excretion = glomerular filtration - reabsorption + tubular secretion

Question 5

Rate of excretion vs clearance?

Answer 5

For many drugs the rate of excretion varies dependent upon drug concentration.

Clearance is a rate constant, it’s the volume of plasma cleared entirely of drug per unit time.

Question 6

What is the normal glomerular filtration rate?

Answer 6

125ml/min

Question 7

What is clearance affected by?

Answer 7

Glomerular filtration rate.

Question 8

Solid sites of excretion?

Answer 8

Faeces, hair

Question 9

Fluid site of excretion?

Answer 9

Urine, bile, sweat, tears and breast milk

Question 10

Gas sites of excretion?

Answer 10

Exhaled breath

Question 11

What are factors that determine filtration of drugs?

Answer 11

Molecular size - majority of drugs are small enough except heparin & biologics
Charge - glomerular capillary walls are -ve charged. So filtration of anions may be reduced.
Protein binding

Question 12

Molecular size of filtration?

Answer 12

Molecules of a weight of less than 20 kDA can pass freely.

Question 13

Which site of the kidney is most important for excretion?

Answer 13

Tubules

Question 14

What is a normal urine pH range?

Answer 14

4.5 - 7.8

Question 15

How does protein binding affect the filtration of drugs?

Answer 15

Only free drugs can be filtered

Question 16

What can renal excretion be affected by?

Answer 16

Any pathology that can reduce glomerular filtration will reduce drug excretion.

Question 17

What are the therapeutic benefits of manipulating urine pH for drug excretion?

Answer 17

This can be done in overdose and poisoning

For example salicylate overdose

Question 18

What are the influences on renal excretion?

Answer 18

Filtrate or urine flow = faster/increased urine will reduce time and conc gradient
Diuretics = increases urine output
Disease states = acute conditions can lead to reduced filtration

Question 19

What are the factors that can affect biliary/ hepatic excretion?

Answer 19

Disease states = acute/chronic liver disease alters efficiency of metabolic processes
Drug interactions can induce or inhibit CYP450 enzyme system