Elimination

Question 1

What is elimination the sum of?

Answer 1

Metabolism and excretion

Question 2

Give an example of two drugs which are excreted largely unchanged

Answer 2

Benzylpenicilin and Gentamicin

Question 3

What is the most important pathway for drug and metabolite excretion?

Answer 3

Renal excretion

Question 4

Give 6 ways in which drugs and their metabolites can be excrete from the body

Answer 4

1. Bile/Faeces
2. Lungs
3. Saliva
4. Sweat
5. Tears
6. Milk

Question 5

What is the calculation for renal excretion?

Answer 5

Renal excretion = (filtration + secretion) - reabsorption

Question 6

What are the 4 stages in filtration at the nephron?

Answer 6

1. Filtration
2. Reabsorption
3. Secretion
4. Excretion

Question 7

What sort of drugs are not filtered at the glomerulus?

Answer 7

Drugs bound to plasma proteins

Question 8

What is the main determinant of whether or not a substance will be filtered by the glomerulus?

Answer 8

Molecular weight

Question 9

What size of molecule is the glomerulus freely permeable to and what is the cut off point?

Answer 9

<2kDA

70kDa

Question 10

What are the cells in the glomerulus called?

Answer 10

Podocytes

Question 11

What are the arterioles that enter and exit the glomerulus called?

Answer 11

Afferent (entering)

Efferent (exiting)

Question 12

Where are OAT and OCT systems located?

Answer 12

Proximal tubule and on the basolateral and apical surfaces of tubule epithelial cells

Question 13

What are the 2 distinct steps in transporting substances from plasma into the lumen of the proximal tubule?

Answer 13

1. Cellular uptake across the basolateral cell surface

2. Efflux into the tubule lumen across the apical surface

Question 14

What provides the energy for transport of anions and cations across the tubule cells?

Answer 14

Ion gradients across the cell surfaces (Na+ gradient used to power anion transport across basolateral cell surface and cation transport across apical surface)

Question 15

What are OATs responsible for?

Answer 15

Secretion of anionic drugs such as benzylpeniilin, methotraxate and ibuprofen, as well as phase two metabolites such as glucuronide and suphates.

Question 16

What are OCTs responsible for?

Answer 16

Renal excretion of weakly basic drugs such cimetidine and quinie

Question 17

How can you remember that benzylpenecilin is directly excreted without being metabolised?

Answer 17

It could be collected, purified and reused

Question 18

What does Probenecid do?

Answer 18

Blocks OATs by competing for transport and inhibiting the tubular secretory system responsible for secretion of weak acids, increases the half-life of penicillin

Question 19

Why is urine produced so much slower than blood is filtered?

Answer 19

Reabsorption as filtrate passes down the nephron

Question 20

How can lipophilic molecules be reabsorped?

Answer 20

Diffusing down the concentration gradient back into the blood

Question 21

Which form of drugs are easily excreted?

Answer 21

Ionised form

Question 22

What can affect the reabsorption of weak acids and bases?

Answer 22

pH of urine

Question 23

What does an acidic urine favour?

Answer 23

Reabsorption of weak acids (less of the drug will be ionised)

Question 24

Why doesn’t an alkaline urine result in more excretion?

Answer 24

More of the drug will be in the lipophilic unionised form

Question 25

What can biliary excretion result in?

Answer 25

Enterohepatic cycling

Question 26

What is methadone used for and how is it excreted?

Answer 26

Treating heroin addictions, excreted into bile

Question 27

What happens to methadone in the small intestine?

Answer 27

Some of the drug is reabsorped and so is available for excretion into the bile again

Question 28

What are the main mechanisms for inactivation and preparation for clearance of a variety of drugs?

Answer 28

Glucuronide and sulphate conjugation

Question 29

What do bacteria of the lower GIT secrete?

Answer 29

Beta-glucuronidase

Question 30

What does Beta-glucuronidase do?

Answer 30

Deglucuronidate a variety of drugs from the intestine, results in release of active drug and enables its reabsorption.

Question 31

Why can antibiotics result in failure of oral contraceptives?

Answer 31

Result in a reduction in bacteria in the GIT, a reduction in recycling of drugs and an increase in their secretion