The Nurse Prescribed Valproic Acid Which Would the Nurse Question Female Who Wants to Start a Family

Continuing Education Activity

Valproic acid is an anticonvulsive and mood stabilizer medication. It is extensively used in the adult population to treat convulsions, migraines, and bipolar disorders. This activity will highlight the mechanism of action, adverse issue profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team) in the handling of patients with epilepsy and related conditions.

Objectives:

• Place the machinery of action of valproic acid.

• Describe the adverse effects of valproic acid.

• Review the appropriate monitoring for patients receiving valproic acrid.

• Summarize inter-professional person team strategies for improving care coordination and communication to advance valproic acrid therapy and improve outcomes.

Access costless multiple choice questions on this topic.

Indications

Valproic acid is a branched, and curt-chain fatty acid is a derivative of naturally occurring valeric acid. Valproic acid's main apply is as an anti-seizure medication, besides every bit in migraine, bipolar, mood, and anxiety disorders. Recent work has also demonstrated its efficacy as adjuvant therapy in HIV, cancer, and neurodegenerative diseases equally its histone deacetylase (HDAC) inhibition belongings. Valproic acrid is a widely used therapy for pediatric epilepsy for its multiple targets and acceptable safe contour. The highly variable dose requirements and interactions with a wide range of drugs warrant regular patient follow-up and therapeutic drug monitoring. Nonetheless, the clinical and adverse drug effects correlate poorly with the serum concentrations of the drug.

Divalproex sodium is the stable, coordinated compound of sodium valproate and valproic acrid. Due to its characteristic broad spectrum anticonvulsive action, divalproex sodium is used to treat a wide range of seizure disorders such as myoclonic epilepsy syndromes, absence epilepsy, generalized convulsions, fractional seizures, and status epilepticus.[1][two] Divalproex sodium is as well efficient in managing acute depressive episodes of bipolar mood disorder and severe manic or mixed episodes.[three] Its utilize has significantly increased over the by decades as a mood stabilizer as well as replacing lithium. All the same, a retrospective cohort study of patients with bipolar found that patients treated with lithium had a lower take a chance of suicide endeavour and suicide expiry than when treated with divalproex sodium.[4] Nevertheless, the 2002 APA Guidelines recommendation for treatment of severe manic or mixed episodes is the initiation of lithium or divalproex sodium plus an atypical antipsychotic as first-line therapy.

Patients who experience less severe events tin can have treatment with divalproex, lithium, or an singular antipsychotic as monotherapy. Lamotrigine is a modern antiepileptic agent that has received approval for the prevention of depressive episodes in bipolar disorder. The pharmacological guidelines for treating bipolar disorder remain circuitous and recommend augmentation with lamotrigine for patients who answer partially to combined therapy with lithium and divalproex.[5][vi] Caution is necessary as valproic acrid increases the emptying one-half-life of lamotrigine.[vii] Furthermore, valproic acid has become widely recognized for the prophylaxis of migraine headaches since approved by the FDA for this indication in 1996.[8] In the pediatric population, valproic acid has shown promising efficacy in treating bipolar mood disorder and conduct disorder and targeting symptoms of irritability, aggression, and impulsivity.[7] Research on the use of valproic acid in cancer therapy is nevertheless in its infancy and provides insight into new areas of its application.[9]

Mechanism of Activeness

Valproic acrid exhibits its pharmacologic effects in a couple of ways, such as by interim on GABA (γ aminobutyric acid) levels in the CNS, blocking voltage-gated ion channels, and inhibiting histone deacetylase. Impaired GABAergic inhibitory action is established pathophysiology of seizure initiation and propagation, given that controlling this pathway a potential target for antiepileptic drugs. GABA is synthesized from α-ketoglutarate through the tricarboxylic acid(TCA) cycle and metabolized into succinate semialdehyde and and so to succinate by GABA transaminase and succinate semialdehyde dehydrogenase, respectively. Previous studies have shown that valproic acid inhibits GABA transaminase and succinate semialdehyde dehydrogenase, increasing the GABA concentration by reducing its deposition (Figure-ane).

Valproic acid may also exert antiepileptic effects by reducing the high-frequency firing of neurons past voltage-gated sodium, potassium, and calcium aqueduct blockade. Valproic acid modulates the biochemical phenomenon of aureola and affects nociception by modulating GABA and/or glutamate-mediated neurotransmission. In neuropathic hurting, it has been demonstrated that valproic acid blocks neurogenic inflammation by GABA-A receptor-mediated inhibition. Recently, valproic acrid showed to be an inhibitor of histone deacetylase (HDAC), particularly HDAC1, as well every bit other HDAC. Histone deacetylase inhibition potentially upregulates the expression of genes that regulates apoptosis and antitumor action.[ten]

Additionally, valproic acid affects signaling systems similar the Wnt/Beta-Catenin and ERK pathways, which similarly interfere with inositol and arachidonate metabolism. Valproate use plays a role in the expression of multiple genes involved in prison cell survival, transcription regulation, ion homeostasis, signal transduction, and cytoskeletal modifications. Both immediate biochemical effect and genomic influences as a long-term outcome can explain the underlying issue of valproic acid in treating all three indications listed above.[11][12][ten][13]

Administration

Valproic acrid is administered orally in tablet class and sprinkles or capsules. The tablet is bachelor in a delayed-release class 125 mg, 250 mg, and 500 mg or an extended-release form of 250 mg and 500 mg. Capsules are bachelor in 125 mg forcefulness.

For the Treatment of Epilepsy

• Valproic acid can be used as monotherapy or as adjunctive therapy in complex partial seizures. The dosage is usually started at 10 to 15 mg/kg/mean solar day, not to exceed sixty mg/kg/day. If daily doses exceed 250 mg, it is given in divided doses.

For the Treatment of Mania

• The initial dose for handling of mania is 250 mg 3 times a day.

• For the ER form, the initial dose is 25 mg/kg once a day, with a rapid increase of upward to 60 mg/kg/day in an effort to achieve the desired clinical issue.

For Migraine Prophylaxis

• Valproic acid's initial dose indicated in migraine prophylaxis is 250 mg twice a mean solar day for one week.

• The ER form tin be started at 500 mg one time daily for 1 week. The dose tin be increased upward to grand mg/twenty-four hours if needed.

Therapeutic Range

• Epilepsy: fifty to 100 mcg/ml total valproate

• Mania: l to 125 mcg/ml total valproate

• It takes about 14 days for valproic acid to reach maximum concentration.

Dose Modifications

• Renal harm: no adjustment needed

• Hepatic damage: administer with circumspection and in lower doses. Valproic acid is contraindicated in cases of severe hepatic harm.

Adverse Effects

Serious Reactions

Valproic acid has multiple serious adverse reactions such as hepatotoxicity, hallucinations, suicidality, psychosis, toxic epidermal necrolysis, Steven Johnson Syndrome, anaphylaxis, hyponatremia, SIADH, pancreatitis, thrombocytopenia, pancytopenia, hyperammonemia, myelosuppression, hypothermia, aplastic anemia, bleeding, erythema multiforme, polycystic ovarian syndrome, cognitive pseudo atrophy, encephalopathy, and coma. Abrupt discontinuation of the drug tin cause withdrawal seizures.

Common Reactions

More common reactions that have been reported in patients using valproic acid are headache, abdominal hurting, somnolence, dizziness, thrombocytopenia, asthenia, nausea & vomiting, diarrhea, dizziness, tremor, weight changes, alopecia, constipation, emotional lability, insomnia, petechiae & ecchymosis, depression, rash, nervousness, ambition changes, ALT and AST meridian, tinnitus, blurred vision, nystagmus, photosensitivity, myalgia, and dyspnea.

Contraindications

Valproic acid is contraindicated in patients with hepatic disorders, pregnant hepatic impairment, hypersensitivity to components of the drug and class of drug, urea cycle disorders, mitochondrial disorders, or suspected disorders in patients <2-year-old, and pregnancy (for migraine headache prophylaxis use of valproic acid).

Also, valproic acid utilize requires circumspection in patients nether 2 years old, pediatric, elderly, renal impairment, organic brain disorders, head injury, mental retardation with seizure disorders, congenital metabolic disorders, hereditary mitochondrial disorders, multiple anticonvulsant treatments, myelosuppression, decreased GI transit time, hepatic disease, an active or a history of depression, and bleeding risk.

Black Box Warnings

• Serious or fatal hepatic failure has been reported during the get-go six months of treatment. Patients <2-yr-old are in greater danger of hepatic toxicity. There is an increased risk of fatality in anticonvulsant polytherapy. In older patients, hepatotoxicity may present with symptoms of weakness, languor, anorexia, facial edema, vomiting, and loss of seizure control; monitoring symptoms and LFTs at baseline and then ofttimes is recommended, peculiarly during the starting time 6months of treatment.

• The use of valproic acid in patients with mitochondrial disease (POLG-related Mitochondrial disorders) has been demonstrated to increment the risk of hepatotoxicity and death. Valproic acid should just be used in patients over ii years old with suspected Mitochondrial disorders who have failed to answer to other anticonvulsant treatments, with frequent monitoring of LFT and POLG mutation screening.

• It tin crusade life-threatening pancreatitis. Cases of hemorrhagic-pancreatitis with rapid progression to expiry have been reported in all ages regardless of treatment duration. If patients have symptoms of pancreatitis such as nausea, vomiting, abdominal pain, or anorexia, advise them to discontinue the medication and start alternative treatment based on clinical indication.[14][15]

• It tin can crusade severe congenital malformations such as neural tube defects and lower IQ scores after in-utero exposure. Additionally, in-utero exposure to valproic acid correlates with an increased risk of autism spectrum disorders in children.[16][17] The use of valproic acid in meaning women for migraine headaches is contraindicated unless there is no other alternative anticonvulsant therapy. According to APA guidelines, boosted screening is recommended for women with bipolar disorder who cull to proceed taking valproic acid during pregnancy.[18]

Monitoring

• LFTs should exist monitored at baseline and then frequently, especially during the first six months of handling or in the presence of hereditary mitochondrial disease.

• CBC with differential, coagulation test, and ammonia should exist monitored at baseline, periodically, before planned surgery, and during pregnancy.

• Screen for symptoms of depression, behavior changes, and suicidality.

• Serum Drug level (therapeutic level for epilepsy: l to 100 mcg/ml; and for mania 50 to 125 mcg/ml) and toxic levels: >175 mcg/ml (before forenoon dose). Every bit valproate is poly peptide-bound, it is important to test the free levels in the presence of hypoalbuminemia. The concentration of the total may be inaccurate.

Enhancing Healthcare Squad Outcomes

Valproic acid is a widely used medication having efficacy in treating multiple neuropsychiatric disorders. A wide range of indications involves multiple medical specialties administering therapy with valproic acid appropriately. Thus, an interprofessional healthcare team, including clinicians (MDs, DOs, NPs, PAs), nurses, and pharmacists, with knowledge of its contraindications, dose adjustments, and potential agin effects, is necessary for health care workers to ensure patient safety and the best outcome. By exercising collaborative efforts and open communication, dosing and management of valproic acid can optimize patient therapy for its various indications. [Level five]

Review Questions

Figure

Effigy-one: Mechanism of activeness of valproic acid. Figure demonstrates the metabolic pathway of GABA synthesis and metabolism by alfa-ketogluterate dehydrogenase, GABA transaminase and Succinate dehydrogenase. Valproic acid inhibits the two downstream catabolic (more...)

References

i.

Willmore LJ. Divalproex and epilepsy. Psychopharmacol Balderdash. 2003;37 Suppl 2:43-53. [PubMed: 15021860]

2.

Olsen KB, Taubøll E, Gjerstad L. Valproate is an effective, well-tolerated drug for handling of condition epilepticus/serial attacks in adults. Acta Neurol Scand Suppl. 2007;187:51-iv. [PubMed: 17419829]

3.

Bond DJ, Lam RW, Yatham LN. Divalproex sodium versus placebo in the handling of acute bipolar low: a systematic review and meta-analysis. J Affect Disord. 2010 Aug;124(iii):228-34. [PubMed: 20044142]

4.

Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D. Suicide chance in bipolar disorder during treatment with lithium and divalproex. JAMA. 2003 Sep 17;290(eleven):1467-73. [PubMed: 13129986]

5.

Calabrese JR, Vieta Eastward, Shelton MD. Latest maintenance data on lamotrigine in bipolar disorder. Eur Neuropsychopharmacol. 2003 Aug;13 Suppl 2:S57-66. [PubMed: 12957721]

half-dozen.

López-Muñoz F, Shen WW, D'Ocon P, Romero A, Álamo C. A History of the Pharmacological Treatment of Bipolar Disorder. Int J Mol Sci. 2018 Jul 23;19(7) [PMC free article: PMC6073684] [PubMed: 30041458]

7.

Rana Chiliad, Khanzode L, Karnik N, Saxena Thousand, Chang K, Steiner H. Divalproex sodium in the treatment of pediatric psychiatric disorders. Expert Rev Neurother. 2005 Mar;5(2):165-76. [PubMed: 15853487]

8.

Freitag FG. Divalproex sodium extended-release for the prophylaxis of migraine headache. Good Opin Pharmacother. 2003 Sep;4(9):1573-viii. [PubMed: 12943487]

9.

Činčárová Fifty, Zdráhal Z, Fajkus J. New perspectives of valproic acid in clinical practice. Expert Opin Investig Drugs. 2013 Dec;22(12):1535-47. [PubMed: 24160174]

ten.

Ghodke-Puranik Y, Thorn CF, Lamba JK, Leeder JS, Song W, Birnbaum AK, Altman RB, Klein TE. Valproic acid pathway: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2013 Apr;23(4):236-41. [PMC free commodity: PMC3696515] [PubMed: 23407051]

11.

Owens MJ, Nemeroff CB. Pharmacology of valproate. Psychopharmacol Balderdash. 2003;37 Suppl two:17-24. [PubMed: 14624230]

12.

Löscher W. Bones pharmacology of valproate: a review after 35 years of clinical use for the handling of epilepsy. CNS Drugs. 2002;16(10):669-94. [PubMed: 12269861]

13.

Rosenberg Yard. The mechanisms of action of valproate in neuropsychiatric disorders: tin can we see the woods for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. [PubMed: 17514356]

14.

Cofini M, Quadrozzi F, Favoriti P, Favoriti 1000, Cofini G. Valproic acrid-induced acute pancreatitis in pediatric age: case series and review of literature. G Chir. 2015 Jul-Aug;36(4):158-60. [PMC costless article: PMC4732585] [PubMed: 26712070]

xv.

Jones MR, Hall OM, Kaye AM, Kaye AD. Drug-induced astute pancreatitis: a review. Ochsner J. 2015 Bound;15(one):45-51. [PMC free article: PMC4365846] [PubMed: 25829880]

16.

Chomiak T, Turner N, Hu B. What Nosotros Have Learned near Autism Spectrum Disorder from Valproic Acid. Patholog Res Int. 2013;2013:712758. [PMC free commodity: PMC3871912] [PubMed: 24381784]

17.

Nicolini C, Fahnestock Grand. The valproic acid-induced rodent model of autism. Exp Neurol. 2018 Jan;299(Pt A):217-227. [PubMed: 28472621]

18.

Gotlib D, Ramaswamy R, Kurlander JE, DeRiggi A, Riba M. Valproic Acrid in Women and Girls of Childbearing Age. Curr Psychiatry Rep. 2017 Sep;nineteen(nine):58. [PubMed: 28726062]

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Source: https://www.ncbi.nlm.nih.gov/books/NBK559112/

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