Valproic Acid Mechanism of Action

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the time to peak for oral valproic acid when taken before a meal?

2 to 4 hours

1 to 3 hours (correct)

Immediate peak

6 to 8 hours

What is the therapeutic range for valproic acid in generalized, partial, and absence seizures?

75 – 125 mg/L

50 – 100 mg/L (correct)

50 – 125 mg/L

100 – 150 mg/L

What is the recommended initial dosage of valproic acid for pediatric patients?

20-25 mg/kg/day

10-15 mg/kg/day (correct)

5-10 mg/kg/day

15-20 mg/kg/day

Why is IV valproate not recommended for post-traumatic seizure prophylaxis?

Due to increased mortality Signup and view all the answers

What should be monitored closely in patients with renal impairment taking valproic acid?

Renal function Signup and view all the answers

What is the classification system used to assess liver dysfunction in patients taking valproic acid?

Child-Pugh score Signup and view all the answers

What is the effect of high urea levels on valproic acid binding?

Decreased protein binding Signup and view all the answers

When should blood samples be taken for valproic acid level monitoring?

Just before next dose Signup and view all the answers

What is the primary use of Valproic Acid?

To treat generalized, partial, and absence seizures Signup and view all the answers

What is the bioavailability of Valproic Acid in sustained release tablets?

80-90% Signup and view all the answers

What is the therapeutic range for Valproic Acid in treating psychiatric disorders?

50-125 mg/L Signup and view all the answers

What is the effect of high concentrations of Valproic Acid on its binding to serum albumin?

The binding becomes saturated Signup and view all the answers

What is the volume of distribution of Valproic Acid in pediatric patients?

0.22 (+ 0.05) L/kg Signup and view all the answers

What is the percentage of Valproic Acid that is bound to serum albumin?

90-95% Signup and view all the answers

What is the level of albumin associated with high valproic acid unbound fraction in plasma?

Below 30 g/L Signup and view all the answers

What is the main route of elimination of valproic acid?

Hepatic metabolism Signup and view all the answers

What is the correlation of clearance of valproic acid in obese patients?

Correlates better with ideal body weight Signup and view all the answers

What is the effect of liver dysfunction on valproic acid clearance?

Decreases clearance Signup and view all the answers

What is a possible cause of displacement of valproic acid from albumin?

All of the above Signup and view all the answers

What is a possible cause of increased metabolism of valproic acid?

Induction of hepatic enzymes Signup and view all the answers

In which situation is monitoring recommended?

When the patient's regimen is changed Signup and view all the answers

What is measured in a full blood count?

Red blood cells and platelets Signup and view all the answers

What is a rare side effect of valproic acid?

Hyperammonemic encephalopathy Signup and view all the answers

In which patients may hemodialysis/hemoperfusion be reserved?

Patients with severe metabolic disturbance Signup and view all the answers

What is monitored every 4-6 hours until the concentrations are clearly decreasing?

Valproic acid concentrations Signup and view all the answers

In which patients may Naloxone be considered?

Patients with CNS depression Signup and view all the answers

Study Notes

Mechanism

Valproic acid is used to treat generalized, partial, and absence seizures, as well as migraines and psychiatric disorders.
It has a wider spectrum of activity than other antiepileptic drugs.

Pharmacokinetic

Bioavailability: • Intravenous: 100% • Oral: 100% • Sustained Release Tablet: 90% • Extended Release Tablet: 80-90%
Volume of Distribution (Vd): • Pediatric: 0.22 (+ 0.05) L/kg • Adults: 0.15 (+ 0.10) L/kg
Therapeutic range: • Seizures: 50-100 mg/L • Psychiatric Disorder: 50-125 mg/L

Volume of Distribution (Vd)

Valproic acid is highly bound to serum albumin (90-95%).
Binding becomes saturated within the therapeutic range (above 50 mg/L), leading to nonlinear pharmacokinetics.
Factors affecting unbound valproic acid fraction: • Hypoalbuminemia • Liver disease • Nephrotic syndrome • Cystic fibrosis • Trauma • Malnourishment • Elderly • Displacement by endogenous or exogenous substances

Metabolism

Valproic acid metabolism is induced by other drugs that enhance hepatic enzyme activity.
One metabolite, 4-hydroxy-valproic acid, may be associated with hepatotoxicity.
Elimination: mostly through hepatic metabolism (>95%) and minimally through renal route (<5%).
Clearance (CL) correlates better with ideal body weight than total body weight in obese patients.
Liver dysfunction reduces valproic acid clearance.

Half-Life

Pediatric: 6-8 hours
Adult: 12-18 hours

Time to Peak

Oral: 1-3 hours (before meal), 6-8 hours (after meal)
Intravenous: at the end of 1 hour infusion

Indication and Therapeutic Range

Generalized, partial, and absence seizures: 50-100 mg/L
Mania, anxiety, depression, psychosis, and substance-abuse withdrawal: 50-125 mg/L

Therapeutic Dose

Initial dose: 10-15 mg/kg/day PO
Dose increase: 5-10 mg/kg/week to achieve optimal clinical response
Maximum dose: 60 mg/kg/day

Special Considerations

Valproic acid concentrations above 100 mg/L may be required in patients with partial seizures.
IV Valproate is not recommended for post-traumatic seizure prophylaxis in patients with acute head trauma.
Valproate should be withdrawn gradually to minimize the potential of increased seizure frequency.

Renal and Hepatic Impairment

Renal impairment: no dosage adjustment necessary, but renal function needs to be monitored closely.
Hepatic impairment: patients with existing liver disease should be classified according to liver dysfunction index (Child-Pugh score) before initiation of the drug.

Interaction

Valproic acid is an enzyme inhibitor and is subject to enzyme induction.

Monitoring

Steady state: 2-4 days
Sampling time: 30 minutes or just before next dose
Monitoring is recommended in certain conditions, including: • Initiation of therapy • Change in dosing regimen • Addition of other antiepileptic drugs • Change in patient's clinical course • Claims of valproic acid side effects

Monitoring Parameters

Liver enzymes
Full blood count with platelets
Serum ammonia (with symptoms of lethargy, mental status change)
Body weight
Blood pressure
Heart rate

Adverse Drug Reactions

Side effects: alopecia, pancreatitis, hyperammonemic encephalopathy, hepatotoxicity, weight gain
Patients at higher risk: young patients, especially those with hepatic failure

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz covers the mechanism of action of Valproic Acid, an antiepileptic drug used to treat various seizure disorders and psychiatric conditions. It also discusses its use in preventing migraines and its comparison with other antiepileptic medications.