Valproic Acid is a synthetic derivative of propylpentanoic acid with antiepileptic properties and potential antineoplastic and antiangiogenesis activities. In epilepsy, valproic acid appears to act by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. This agent’s antitumor and antiangiogenesis activities may be related to the inhibition of histone deacetylases and nitric oxide synthase, which results in the inhibition of nitric oxide synthesis.
Valproic acid supplied as the sodium salt valproate semisodium or divalproex sodium is a fatty acid with anticonvulsant properties used in the treatment of epilepsy & primarily used to treat epilepsy and bipolar disorder and to prevent pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine headaches. It is useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-dependent sodium channels.
Mechanism of Action of Valproic Acid
Valproic Acid dissociates to the valproate ion in the gastrointestinal tract and then binds to and inhibits GABA transaminase. The drug’s anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.
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Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC). /A/ previous study has demonstrated that VPA pretreatment reduces lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity through the inhibition of microglia over-activation. The aim of this study was to determine the mechanism underlying VPA-induced attenuation of microglia over-activation using rodent primary neuron/glia or enriched glia cultures. Other histone deacetylase inhibitors (HDACIs) were compared with VPA for their effects on microglial activity. We found that VPA induced apoptosis of microglia cells in a time- and concentration-dependent manner. VPA-treated microglial cells showed typical apoptotic hallmarks including phosphatidylserine externalization, chromatin condensation, and DNA fragmentation. Further studies revealed that trichostatin A (TSA) and sodium butyrate (SB), two structurally dissimilar HDACIs, also induced microglial apoptosis. The apoptosis of microglia was accompanied by the disruption of mitochondrial membrane potential and the enhancement of acetylation levels of the histone H3 protein. Moreover, pretreatment with SB or TSA caused a robust decrease in LPS-induced pro-inflammatory responses and protected DA neurons from damage in mesencephalic neuron-glia cultures. Taken together, /these/ results shed light on a novel mechanism whereby HDACIs induce neuroprotection and underscore the potential utility of HDACIs in preventing infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation-related neurodegenerative disorders such as Parkinson’s disease
Indications of Valproic Acid
- Bipolar disorder
- Epilepsy
- Seizure prevention
- Cluster-Tic syndrome
- Hyperekplexia
- Mania
- Migraine prevention
- Schizoaffective disorder
- Seizures
- Epilepsies
- A migrainous headache
- Schizophrenic disorders
- Acute manic episode
- For treatment and management of seizure disorders, mania, and prophylactic treatment of a pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine headache. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome.
Contra Indications of Valproic Acid
- High amount of ammonium in the blood
- Low amount of albumin proteins in the blood
- Porphyria
- Decreased blood platelets
- Having thoughts of suicide
- Depression
- Organic mental disorder
- Liver problems
- Acute infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation of the pancreas
- Pregnancy
- Ornithine carbamoyltransferase deficiency
- Poisoning by drug valproic Acid
- Hereditary disease causing neurologic dysfunction
- Urea cycle disorder
The Dosage of Valproic Acid
Strengths: 125 mg; 200mg; 500 mg ;100 mg/mL; 250 mg; 250 mg/5 mL
Epilepsy
Complex partial seizures
- Initial dose: 10 to 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
- Maintenance dose: 10 to 60 mg/kg daily
- Maximum dose: 60 mg/kg daily
Simple and complex absence seizures
- Initial dose: 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
- Maintenance dose: 10 to 60 mg/kg daily
- Maximum dose: 60 mg/kg daily
Pediatric Epilepsy
10 years or older
- Initial dose: 10 to 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
- Maintenance dose: 10 to 60 mg/kg daily
- Maximum dose: 60 mg/kg daily
Simple and complex absence seizures
- Initial dose: 15 mg/kg orally or IV daily; increase by 5 to 10 mg/kg per week if necessary according to clinical response
- Maintenance dose: 10 to 60 mg/day
Side Effects of Valproic Acid
The most common
- nausea, vo miting, stomach pain, indigestion, constipation, diarrhea;
- fever, flu symptoms, cough, sore throat, sneezing, runny nose;
- nervousness, depression, sleep problems (insomnia);
- headache, dizziness, drowsiness, memory problems, unusual thoughts;
- rash, hair loss, bruising;
- weakness, tremors, problems with balance or walking;
- swelling in your hands or feet;
- vision problems, ringing in your ears; or
- changes in appetite, weight gain.
More common
- Black, tarry stools
- bleeding gums
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blood in the urine or stools
- confusion
- cough or hoarseness
- crying
- delusions
- dementia
- depersonalization
- diarrhea
- difficult or labored breathing
- dysphoria
- euphoria
- fever or chills
Less common
- Abnormal dreams
- absence of or decrease in body movement
- anxiety
- bloody nose
- bloody or cloudy urine
- blurred vision
- burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
- change in personality
- change in walking and balance
- changes in patterns and rhythms of speech
- chest pain
- lack of appetite
- lack of coordination
- large, flat, blue or purplish patches in the skin
- leg cramps
- lip smacking or puckering
- loss of bladder control
Drug Interactions of Valproic Acid
Valproic Acid may interact with following drug, suppliments, & may change the efficasy of drugs
- antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine,loratadine)
- antiseizure medications e.g., clobazam, levetiracetam, phenobarbital, phenytoin, , valproic acid, zonisamide)
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- captopril
- celecoxib
- chloroquine
- cholecalciferol
- cyclosporine
- dantrolene
- domperidone
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- gabapentin
- H2 antagonists (e.g., famotidine, ranitidine)
- mirabegron
- montelukast
- non-steroidal anti-inflammatory medications (NSAIDs;e.g., diclofenac, ibuprofenserotonin antagonists (anti-emetic medications;, naproxen)
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine,citalopram)
- e.g., granisetron,ondansetron)
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin,simvastatin)
- theophylline
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine,
Pregnancy & Lactation of Valproic Acid
Valproate was initially Pregnancy Category D, but it is now Category X
Pregnancy
There is an increased risk of birth defects for a child whose mother takes valproic acid during pregnancy. Although rare, valproic acid may cause a defect of the spine called spina bifida or slowed or reduced mental development. Before becoming pregnant, women with epilepsy should speak to their doctor about options for seizure medications. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication passes into breast milk. If you are a breastfeeding mother and are taking valproic acid it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. As a general rule, women who are taking valproic acid should not breastfeed.
