Anticonvulsant toxicity - VPA Flashcards
F of VPA (valproic acid)?
~100%
Percent plasma protein binding at therapeutic levels of VPA (350µmol/L)?
90%
What happens to percent plasma protein binding of VPA as plasma levels increase beyond therapeutic levels?
It decreases (more unbound fraction due to plasma protein saturation)
How is VPA mainly excreted?
Renally
Normal elimination t1/2 of VPA?
5-20h
T1/2 of VPA in overdose?
up to 30h
What compound is depleted during VPA chronic use and overdose?
Carnitine
What can reduced carnitine levels (due to VPA tox) result in?
- increased 4-en-valproic acid levels
- accumulation of ammonia (due to interruption of carnitine-based esterification process of urea cycle) > cerebral edema
Normal therapeutic VPA levels?
350-700 µmol/L
VPA levels that produce mild sx’s?
> 700 µmol/L
VPA levels that produce srs sx’s or that may be fatal?
5500-7000+ µmol/L
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.
T
CNS sx’s of VPA toxicity?
- CNS depression
- lethargy
- coma
- cerebral edema (due to ammonia accumulation)
- seizures
GI sx’s of VPA tox?
Anorexia, N/V, pancreatitis (rare)
Respiratory sx’s of VPA tox?
resp depression
CV sx’s of VPA tox?
hypotn (usually if > 5550 µmol/L)
Metabolic/electrolite sx’s of VPA tox?
- hyperammonemia
- metabolic acidosis
- hypocalcemia
- hypernatremia
Plasma levels of VPA tox assoc w/ metabolic acidosis?
> 3100 µmol/L
Plasma levels of VPA tox assoc w/ hypocalemia?
> 3100 µmol/L
T or F: There is no hepatotox assoc w/ VPA overdose
F
T or F: There is no renal failure assoc w/ VPA tox
F
What’s the very first thing we should ensure when attending to a pt w/ VPA overdose?
ABCs: Airway, breathing, and circulation
What can be used for VPA toxicity decontamination?
Activated charcoal
T or F: Hemodialysis is NOT recommended during a VPA overdose unless levels are under 9000 µmol/L
F
When is hemodialysis recommended for VPA tox?
When levels are > 9000 µmol/L, shock, cerebral edema is present
T or F: Aside from [VPA] being over 9000 µmol/L, shock, and cerebral edema, hemodialysis should not be used in any other case.
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
When should hemodialysis be stopped for VPA tox tx?
Clinical improvement + [VPA] is between 350-700 µmol/L
T or F: Naloxone may be useful in VPA overdoses
T
When would naloxone be useful in VPA overdose?
If [VPA] is under 1400 µmol/L
Besides naloxone, what’s another possible antidote for VPA overdose?
Carnitine
When would carnitine be stopped during VPA overdose?
When ammonia levels are reduced and pt shows clinical improvement
