2. Applied Pharmacokinetics

Question 1

If digoxin has a t1/2 of roughly 40hrs, how long does it take to reach a steady state in the body?

Answer 1

Roughly a week (3x40hrs - 5x40hrs = 5 - 8.3 days)

Question 2

Does digoxin have a large or small Vd?

Answer 2

Large (~200L, or 7.5L/kg)

Question 3

Where is digoxin predominantly excreted?

Answer 3

The kidneys

Question 4

What does the long t1/2 mean for initiating treatment?

Answer 4

A loading dose is needed

Question 5

What should happen if the pt on digoxin developes renal failure? Why?

Answer 5

Maintenance dose should be decreased, because clearance of the drug will be decreased.

Question 6

What happens in the digitoxic patient?

Answer 6

Bradycardia, vomiting, xanthopsia

Question 7

How should a digitoxic pt be treated?

Answer 7

Hydrate with IV fluids
O2
Discontinue drug
Give activated charcoal for GI tract symptoms

Question 8

How much paracetamol is generally considered an overdose?

Answer 8

~10g

Question 9

How many pathways is paracetamol usually metabolised via?

Answer 9

3

Question 10

How is 60% of paracetamol usually metabolised?

Answer 10

Conjugation with glutathione -> Glucoronide

Question 11

How is 30% of paracetamol usually metabolised?

Answer 11

Conjugation -> Paracetamol sulphate

Question 12

How is 10% of paracetamol usually metaolised?

Answer 12

P450 oxidation -> NAPQI, then conjugated with glutathione -> inactive metabolite

Question 13

What is depleted in paracetamol overdose?

Answer 13

Glutathione

Question 14

What is the significance of glutathione depletion in paracetamol overdose?

Answer 14

NAPQI buildup to toxic levels

Question 15

How is paracetamol overdose treated?

Answer 15

Take blood paracetamol levels 4hrs after the initial overdose.
Activated charcoal (to reduce utake in GI tract)
N-acetlycysteine to replenish glutathione

Question 16

How is loading dose calculated?

Answer 16

LD = Vd x target [Drug]

Question 17

How is target [Drug] calculated?

Answer 17

Usually by weight of pt

Question 18

What else should be taken into account when formulating loading dose?

Answer 18

1. Drug formulation eg salt formation

2. Upper limit of LD regardless of weight