Anticonvulsant toxicity - VPA

Question 1

F of VPA (valproic acid)?

Answer 1

~100%

Question 2

Percent plasma protein binding at therapeutic levels of VPA (350µmol/L)?

Answer 2

90%

Question 3

What happens to percent plasma protein binding of VPA as plasma levels increase beyond therapeutic levels?

Answer 3

It decreases (more unbound fraction due to plasma protein saturation)

Question 4

How is VPA mainly excreted?

Answer 4

Renally

Question 5

Normal elimination t1/2 of VPA?

Answer 5

5-20h

Question 6

T1/2 of VPA in overdose?

Answer 6

up to 30h

Question 7

What compound is depleted during VPA chronic use and overdose?

Answer 7

Carnitine

Question 8

What can reduced carnitine levels (due to VPA tox) result in?

Answer 8

1. increased 4-en-valproic acid levels
2. accumulation of ammonia (due to interruption of carnitine-based esterification process of urea cycle) > cerebral edema

Question 9

Normal therapeutic VPA levels?

Answer 9

350-700 µmol/L

Question 10

VPA levels that produce mild sx’s?

Answer 10

> 700 µmol/L

Question 11

VPA levels that produce srs sx’s or that may be fatal?

Answer 11

5500-7000+ µmol/L

Question 12

T or F: Some ppl won’t tolerate the lower end of the therapeutic levels of VPA, and others won’t respond to the higher end.

Answer 12

T

Question 13

CNS sx’s of VPA toxicity?

Answer 13

1. CNS depression
2. lethargy
3. coma
4. cerebral edema (due to ammonia accumulation)
5. seizures

Question 14

GI sx’s of VPA tox?

Answer 14

Anorexia, N/V, pancreatitis (rare)

Question 15

Respiratory sx’s of VPA tox?

Answer 15

resp depression

Question 16

CV sx’s of VPA tox?

Answer 16

hypotn (usually if > 5550 µmol/L)

Question 17

Metabolic/electrolite sx’s of VPA tox?

Answer 17

1. hyperammonemia
2. metabolic acidosis
3. hypocalcemia
4. hypernatremia

Question 18

Plasma levels of VPA tox assoc w/ metabolic acidosis?

Answer 18

> 3100 µmol/L

Question 19

Plasma levels of VPA tox assoc w/ hypocalemia?

Answer 19

> 3100 µmol/L

Question 20

T or F: There is no hepatotox assoc w/ VPA overdose

Answer 20

F

Question 21

T or F: There is no renal failure assoc w/ VPA tox

Answer 21

F

Question 22

What’s the very first thing we should ensure when attending to a pt w/ VPA overdose?

Answer 22

ABCs: Airway, breathing, and circulation

Question 23

What can be used for VPA toxicity decontamination?

Answer 23

Activated charcoal

Question 24

T or F: Hemodialysis is NOT recommended during a VPA overdose unless levels are under 9000 µmol/L

Answer 24

F

Question 25

When is hemodialysis recommended for VPA tox?

Answer 25

When levels are > 9000 µmol/L, shock, cerebral edema is present

Question 26

T or F: Aside from [VPA] being over 9000 µmol/L, shock, and cerebral edema, hemodialysis should not be used in any other case.

Answer 26

F

It can be used if VPA > 6250 µmol/L, if pt is in a coma, if mechanical ventilation is being used, if pH is less than 7.1, or if there’s hyperammonemia

Question 27

When should hemodialysis be stopped for VPA tox tx?

Answer 27

Clinical improvement + [VPA] is between 350-700 µmol/L

Question 28

T or F: Naloxone may be useful in VPA overdoses

Answer 28

T

Question 29

When would naloxone be useful in VPA overdose?

Answer 29

If [VPA] is under 1400 µmol/L

Question 30

Besides naloxone, what’s another possible antidote for VPA overdose?

Answer 30

Carnitine

Question 31

When would carnitine be stopped during VPA overdose?

Answer 31

When ammonia levels are reduced and pt shows clinical improvement