Pharmacology
Central Nervous System
Which of the following is a well recognised adverse effect of sodium valproate:
Answer:
Side effects:- Gastric irritation, and hyperammonaemia both of which can lead to intense nausea
- Lethargy and confusion
- Weight gain
- Hair loss, with curly regrowth
- Peripheral oedema
- Very rarely, fulminant hepatic failure
- Hyperandrogenism in women
- Thrombocytopenia, leucopenia and red cell hypoplasia
- Pancreatitis
Sodium Valproate
Pharmacology / Central Nervous System
Last Updated: 4th April 2019
Indications
Sodium valproate is effective in controlling tonic-clonic seizures, particularly in primary generalised epilepsy. It is a drug of choice in primary generalised tonic-clonic seizures, focal seizures, generalised absences and myoclonic seizures, and can be tried in atypical absence seizures. It is recommended as a first-line option in atonic and tonic seizures.
Mechanism of Action
Carbamazepine, lamotrigine, valproate and phenytoin act by producing a use-dependent block of neuronal Na+ channels. Their anticonvulsant action is a result of their ability to prevent high-frequency repetitive activity. The drugs bind preferentially to inactivated (closed) Na+ channels, stabilising them in the inactivated state and preventing them from returning to the resting (closed) state, which they must re-enter before they can again open.
Sodium valproate has widespread metabolic effects and monitoring of liver function tests and full blood count is essential. Valproate should not be used in female children, in females of childbearing potential, and pregnant females, unless alternative treatments are ineffective or not tolerated, because of its high teratogenic potential.
Contraindications
Sodium valproate is contraindicated in:
- Acute liver disease
- Acute porphyrias
- Known or suspected mitochondrial disorders (higher rate of acute liver failure and liver-related deaths)
- Personal or family history of severe, drug-related hepatic dysfunction
Side Effects
- Gastric irritation, and hyperammonaemia both of which can lead to intense nausea
- Lethargy and confusion
- Weight gain
- Hair loss, with curly regrowth
- Peripheral oedema
- Very rarely, fulminant hepatic failure
- Hyperandrogenism in women
- Thrombocytopenia, leucopenia and red cell hypoplasia
- Pancreatitis
- Hepatic impairment
Interactions
Valproate is highly protein-bound (up to 94%), and other drugs that are also highly protein bound (e.g. aspirin) may displace valproate from albumin and precipitate toxicity.
Other less strongly protein-bound drugs (for example warfarin) can be displaced by valproate; this may lead to higher free levels and increased therapeutic effect or toxicity of the concomitant drug.
Valproate is metabolised by the liver, so drugs that inhibit cytochrome P450 enzymes (for example erythromycin, fluoxetine, and cimetidine) can increase valproate levels.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
