15B24: Exam Report
Compare and contrast the pharmacology of valproic acid and carbamazepine.
6% of candidates passed this question.
Both these agents are listed as “level B” in the syllabus pharmacopeia and as such a general understanding of each class and relevant pharmacokinetics and pharmacodynamics was expected. Most candidates had better knowledge of valproate than carbamazepine. Some description of the toxicological features for intensive care practitioners was expected.
K2iii / 15B24: Compare and contrast the pharmacology of valproic acid and carbamazepine
Drug
Valproic Acid
Carbamazepine
Use
Valproic Acid
- Tx epilepsy
- Chronic pain
- Mood stabiliser
Carbamazepine
- Tx epilepsy
- Trigeminal neuralgia
- Bipolar disorder
Interestingly Sodium Valproate seems to limit atrial ectopic beats but not an indication for its use – used in epilepsy and psychiatric illness
Carbemazepine is used for focal and generalised seizures. C is not effective for Petit Mal, whereas Valproate is.
C is also used to Tx Schizophrenia
Route
Valproic Acid
PO/IV
Carbamazepine
PO
Benefit of additional IV route of admin for Valproic Acid
MoA
Valproic Acid
Stabilises inactive Na+ channels
Stimulates central GABA inhibitory pathways
Carbamazepine
Unknown MoA
Limits seizure propagation
PD
Valproic Acid
CNS – anticonvulsant
Carbamazepine
CNS – antileptic
CVS – antiarrhythmic, depressing AV conduction
GU – antidiuretic effect
PK
Valproic Acid
A
Rapid & complete
100% OBA
D
90% PPB
VD 0.4L/kg
M
Liver
Oxidation & glucuronidase
E
t ½ B 8 – 20hrs
Metabolites excreted in urine
Clearance 11mL/kg/hr
Carbamazepine
A
100% OBA
D
75% PPB
VD 1L/kg
M
Liver oxidation
Chronic use = induces its own metabolism
E
Unconjugated metabolites excreted in urine
Valproate has some active metabolites
Carbemazepine may require dose adjustment in chronic use
Adverse Effects
Valproic Acid
Hepatic dysfunction
Acute pancreatitis
Hair loss
Oedema
Weight gain
Carbamazepine
H2O toxicity
Rashes
Renal & liver damage
Diplopia
Drowsiness
N&V
Neither of these side effect profiles looks appealing and both would need serum monitoring