K2iii / 15B24: Valproic Acid v Carbamazepine

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

  1. Tx epilepsy
  2. Chronic pain
  3. Mood stabiliser

Carbamazepine

  1. Tx epilepsy
  2. Trigeminal neuralgia
  3. 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