9 & 10 - Anticonvulsants 2 & 3

Question 1

Indications for phenytoin

Answer 1

• Generalized tonic-clonic seizures
• Partial seizures
• Neurogenic pain syndromes

Question 2

Therapeutic range of phenytoin

Answer 2

10-20 mg/L (total)

Question 3

What is important to note about phenytoin?

Answer 3

• Half life is concentration dependent
• Half life decreases at lower concentrations
• Doesn’t produce a linear graph on a ln C vs. time
• Have to use the orbit plots

Question 4

What is Vmax?

Answer 4

Maximum rate at which metabolism can occur

Question 5

What is Km?

Answer 5

• Concentration at which the rate of metabolism is half maximal
• Linear PK is exhibited below this point

Question 6

Which pathways if phenytoin a substrate for?

Answer 6

CYP 2C9 and 2C19

Question 7

How do you adjust phenytoin concentration for hypoalbuminemia?

Answer 7

• C adjusted = C observed / 0.02* albumin + 0.1

- Determine % free based on the adjusted concentration

Question 8

What is normal serum albumin?

Answer 8

35 - 45 g/L

Question 9

How do you adjust phenytoin concentration for hypoalbuminemia and uremia?

Answer 9

C adjusted = C observed / 0.01 * albumin + 0.1

Question 10

What effect does uremia have on phenytoin?

Answer 10

• Slow increases in uremic toxins causes displacement of phenytoin from albumin binding sites
• Transiently increases free drug and drug clearance

Question 11

What assumptions are made when using orbit plots?

Answer 11

• Patient is actually at Css (hasn’t missed a dose in the past week)
• Albumin is normal

Question 12

How do you calculate loading dose?

Answer 12

Change in concentration * Vd / S * F

Question 13

Can you ratio phenytoin doses?

Answer 13

NO!!! Will quickly overdose a patient

Question 14

What is uremia?

Answer 14

• High urea in the blood
• Normal range = 2.8 - 7.1
• Measure of kidney damage

Question 15

Example – phenytoin dose is 350 mg daily. How would you divide it up?

Answer 15

150 mg AM and 200 mg HS

Question 16

What formula would you use for a patient that is uremic but with normal albumin?

Answer 16

The formula for uremia (with 0.01 * albumin in denominator)

Question 17

What is the Fu for valproic acid? What does this mean?

Answer 17

• Fraction excreted unchanged renally = < 5%

- Do not need to adjust dose for renal dysfunction

Question 18

What should be calculated for regular release oral valproic acid?

Answer 18

Peaks and troughs

Question 19

What is the normal half life for valproic acid in children?

Answer 19

7.5 h

Question 20

How can you determine ke based on trough level?

Answer 20

• Change in concentration = dose / Vd
• Peak = trough + change in concentration
• Ke = ln (peak/trough) / change in time

Question 21

Can you ratio doses for valproic acid?

Answer 21

Yes

Question 22

What determines protein binding for valproic acid?

Answer 22

• Serum albumin levels

- Lower albumin = higher free fraction %

Question 23

Which px need adjustments for total valproic acid levels?

Answer 23

Hypoalbuminemic

Question 24

How should you adjust phenytoin levels for px w/ ESRD on dialysis?

Answer 24

• Don’t use the uremia equation, use the hypoalbuminemia equation
• C adjusted = C observed / 0.02 * albumin + 0.1

Question 25

What is the maximum recommended dose of valproic acid in mg/kg/day?

Answer 25

60 mg/kg/day

Question 26

What would you do if a px is on valproic acid and they need to be started on a carbapenem?

Answer 26

• Interaction which decreases valproic acid concentrations drastically
• Switch anticonvulsants