Valproate

Question 1

Valproate Mechanism of Action

Answer 1

• Valproate is an anticonvulsant. It predominantly blocks sodium channels but also enhances the activity of gamma-aminobutyric acid (GABA) at GABA receptors within the central nervous system.
• The active ingredient in sodium valproate is valproate.

Question 2

Valproate Indications

Answer 2

Status epilepticus that has not responded to two doses of midazolam.

Question 3

Valproate Contraindications

Answer 3

Known severe allergy.

Question 4

Valproate Cautions

Answer 4

None

Question 5

Valproate Use in pregnancy/breastfeeding

Answer 5

• Valproate has been demonstrated to increase the risk of harm to the unborn baby. However, this has only been demonstrated with chronic administration
and the balance of risk is in favour of administration if the mother has status epilepticus.
• Small amounts are excreted in breast milk but the balance of risk is in favour of administration if the mother has status epilepticus.

Question 6

Valproate Dose

Answer 6

• 1200 mg for an adult.

* See the paediatric drug dose tables for a child.

Question 7

Valproate Administration

Answer 7

Dissolve each ampoule using 4 ml of 0.9% sodium chloride. Draw up the required dose into one syringe and dilute to a total of 10-20 ml using 0.9% sodium chloride.
• Administer IV over 1-2 minutes, preferably into a running IV line.
• Do not administer IM as this causes muscle necrosis.

Question 8

Valproate Common adverse effects

Answer 8

None

Question 9

Valproate Onset of effect

Answer 9

• 10-20 minutes.

Question 10

Valproate Duration of effect

Answer 10

• 6-12 hours.

Question 11

Valproate Preparation

Answer 11

Ampoule with 400mg powder for reconstitiuion

Question 12

Valproate Pharmacokinetics

Answer 12

• Valproate is predominantly metabolised in the liver.
• There are no significant effects from liver impairment on the initial (loading)
dose.

Question 13

Valproate Common interactions

Answer 13

None

Question 14

Valproate Additional information

Answer 14

• Paramedics must call for backup from an ICP if valproate is to be administered.

Question 15

Valproate Sodium channel explanation

Answer 15

• Blocks neuronal sodium channels
• Binds to inactivated channels, keeps them in a closed state - stops them from opening again and building current that will cause an action potential
• Repetitive depolarisation (opening) of these channels causes them to be inactive more frequently (get tired?)
• As more are inactive, more Valps binds and keeps them closed, this results in decreased activity, and decreased action potentials (seizure activity)

Question 16

Valproate GABA explanation

Answer 16

• GABA is an inhibitory neurotransmitter
• It changes uptake of chloride ions (complex and varied)
• Valproate inhibits re-uptake of GABA, causing increased levels of the neurotransmitter at the synapse
• Results in hyper-polarisation of the post synaptic neuron -> signals are transmitted across the synaptic cleft but “bounce off” the post-synaptic cell