Carboxylic acid derivatives

The drugs in this class are:

• valproate
• valproic acid
• divalproex.

Pharmacokinetics
Valproate is converted rapidly to valproic acid in the stomach.
Divalproex is a precursor of valproic acid that separates into valproic acid
in the GI tract. Valproic acid is a hepatic enzyme inhibitor. It’s absorbed
well, strongly protein bound, and metabolized in the liver. Metabolites and
unchanged drug are excreted in urine. Valproic acid readily crosses the
placental barrier and also appears in breast milk.

Pharmacodynamics
The mechanism of action for valproic acid remains unknown. It’ thought to
increase levels of GABA, an inhibitory neurotransmitter, as well as having
a direct membrane-stabilizing effect.

Pharmacotherapeutics
Valproic acid is prescribed for long-term treatment of:
• absence seizures
• myoclonic seizures
• tonic-clonic seizures
• partial seizures.

Valproic acid may also be useful for neonatal seizures. However, it

must be used cautiously in children younger than age 2, particularly those
receiving multiple anticonvulsants, those with congenital metabolic
disorders or hepatic disease, those with severe seizures and mental
retardation, and those with organic brain disease. For these patients, the
drug carries a risk of potentially fatal liver toxicity (usually within the
first 6 months of treatment). This risk limits the use of valproic acid as a
drug of choice for seizure disorders.

Happy accident
The anticonvulsant properties of valproic acid were actually discovered
when it was being used as a vehicle for other compounds being tested for
anticonvulsant properties. Structurally, valproic acid is unlike other
anticonvulsants. Its mechanism of action isn’t completely understood

Drug interactions
Here are the most significant drug interactions associated with valproic
acid:
• Cimetidine, aspirin, erythromycin, and felbamate may increase levels
of valproic acid.
• Carbamazepine, lamotrigine, phenobarbital, primidone, phenytoin,
and rifampin may decrease levels of valproic acid.
• Valproic acid may decrease the effects of lamotrigine, phenobarbital,
primidone, benzodiazepines, CNS depressants, warfarin, and
zidovudine.
Adverse reactions
Rare, but deadly, liver toxicity has occurred with valproic acid use. The
drug should be used with caution in the patient who has a history of liver
disease. Pediatric patients younger than age 2 are at considerable risk for
developing hepatotoxicity. Most other adverse reactions to valproic acid
are tolerable and dose- related.
These include:
• nausea and vomiting
• diarrhea or constipation
• sedation
• dizziness
• ataxia
• headache
• muscle weakness
• increased blood ammonia level.

Nursing process
Assessment
• Assess the patient’s condition before therapy and regularly
thereafter.
• Monitor the level of the drug in the blood (therapeutic level is 50 to
100 mcg/mL).
• Monitor liver function studies, platelet counts, and prothrombin time
before starting the drug and periodically thereafter.
• Monitor the patient’s response to the drug, especially for adverse
reactions.
• Be aware that the drug may produce false-positive test results for
ketones in urine.
• Assess the patient’s compliance with therapy at each follow-up visit.

Key nursing diagnoses

• Risk for injury related to adverse reactions
• Impaired physical mobility related to sedation
• Noncompliance related to long-term therapy

Planning outcome goals

• The risk of injury to the patient will be minimized.
• The patient will be able to perform ADLs.
• The patient will verbalize factors that contribute to noncompliance.

Implementation
• Administer oral forms of the drug with food to reduce GI irritation.
Don’t give the syrup form to a patient who needs sodium restriction.
Check with the prescriber.
• Dilute the drug with at least 50 mL of a compatible diluent (D5W,
saline solution, lactated Ringer’s solution) if injecting IV and give
over 1 hour. Don’t exceed 20 mg/minute.
• Avoid sudden withdrawal, which may worsen seizures.
• Expect to adjust the dosage according to the patient’s response. In
elderly patients, a reduced starting dose is suggested, with slower
dosage increases.
 • Administer safety precautions if the patient has adverse CNS
reactions to the drug.
• Monitor closely for hepatotoxicity because it may follow nonspecific
symptoms, such as malaise, fever, and lethargy.
Evaluation
• Patient sustains no injury from adverse reactions.
• Patient maintains physical mobility.
• Patient complies with therapy and has no seizures