From the Guidelines
Elevated ammonia levels in a patient taking valproic acid are primarily caused by the drug's interference with the urea cycle in the liver, which can lead to a build-up of toxic ammonia levels, particularly in individuals with underlying urea cycle disorders or liver problems 1. The urea cycle is a critical process by which the body converts ammonia into urea for excretion, and valproic acid can inhibit this cycle, leading to hyperammonemia.
- Key factors that contribute to elevated ammonia levels in patients taking valproic acid include:
- Underlying urea cycle disorders, such as carbamoyl phosphate synthase I (CPS) or ornithine transcarbamylase (OTC) deficiency
- Liver disease or impairment, which can affect the liver's ability to convert ammonia to urea
- High doses of valproic acid, which can increase the risk of hyperammonemia
- Concomitant use of other medications that can affect the urea cycle or liver function
- Symptoms of hyperammonemia can include confusion, lethargy, vomiting, and changes in mental status, and can be life-threatening if left untreated 1.
- Management of elevated ammonia levels in patients taking valproic acid may involve reducing the dose or discontinuing the medication, as well as administering L-carnitine supplementation to help manage the side effect 1.
- It is essential to monitor ammonia levels and liver function regularly in patients taking valproic acid, particularly those with underlying urea cycle disorders or liver problems, to prevent and detect hyperammonemia early 1.
From the Research
Causes of Elevated Ammonia Levels
- Elevated ammonia levels in a patient taking valproic acid (Valproate) can be caused by the medication itself, as seen in a case report of fatal hyperammonemic brain injury from valproic acid exposure 2.
- The exact mechanism is not fully understood, but it is thought that valproic acid can interfere with the body's ability to metabolize ammonia, leading to its accumulation 2.
- Hyperammonemia can also be caused by other factors, such as liver disease, inherited defects in urea cycle enzymes, and certain medications 3, 4.
Pathophysiology of Hyperammonemia
- Ammonia is a toxic substance that can cause neuronal injury and death if it accumulates in the body 2, 3.
- The body normally metabolizes ammonia through the urea cycle, which takes place in the liver and kidneys 3.
- In cases of hyperammonemia, the body's ability to metabolize ammonia is impaired, leading to its accumulation in the blood and tissues 3, 5.
Diagnosis and Treatment of Hyperammonemia
- Hyperammonemia can be diagnosed through blood tests that measure ammonia levels 2, 6.
- Treatment of hyperammonemia depends on the underlying cause, but may include medications such as sodium phenylacetate and sodium benzoate, as well as hemodialysis to remove excess ammonia from the blood 2, 3.
- In cases of valproic acid-induced hyperammonemia, prompt reduction of elevated ammonia levels may prevent permanent neurological injury 2.