Effect of antiepileptic drug (valproic acid) on children growth

Maksoud, Hussein M. Abdel; El-Shazly, Sherif Mahmoud; Saied, Mahmoud Helmy El

doi:10.1016/j.epag.2016.04.001

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…VPA is an anticonvulsant drug with a broad spectrum in the treatment of epilepsy ( 17 ). The use of VPA during pregnancy is known to cause a congenital malformation ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring

et al. 2018

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Valproic acid (VPA) plays a role in histone modifications that eventually inhibit the activity of histone deacetylase (HDAC), and will affect the expressions of genes Pdx1, Nkx6.1, and Ngn3 during pancreatic organogenesis. This experiment was designed to study the effect of VPA exposure in pregnant rats on the activity of HDAC that controls the expression of genes regulating the development of beta cells in the pancreas to synthesize and secrete insulin. This study used 30 pregnant Sprague-Dawley rats, divided into 4 groups, as follows: (1) a control group of pregnant rats without VPA administration, (2) pregnant rats administered with 250 mg VPA on day 10 of pregnancy, (3) pregnant rats administered with 250 mg VPA on day 13 of pregnancy, and (4) pregnant rats administered with 250 mg VPA on day 16 of pregnancy. Eighty-four newborn rats born to control rats and rats administered with VPA on days 10, 13, and 16 of pregnancy were used to measure serum glucose, insulin, DNA, RNA, and ratio of RNA/DNA concentrations in the pancreas and to observe the microscopical condition of the pancreas at the ages of 4 to 32 weeks postpartum with 4-week intervals. The results showed that at the age of 32 weeks, the offspring of pregnant rats administered with 250 mg VPA on days 10, 13, and 16 of pregnancy had higher serum glucose concentrations and lower serum insulin concentrations, followed by decreased concentrations of RNA, and the ratio of RNA/DNA in the pancreas. Microscopical observations showed that the pancreas of the rats born to pregnant rats administered with VPA during pregnancy had low immunoreaction to insulin. The exposure of pregnant rats to VPA during pregnancy disturbs organogenesis of the pancreas of the embryos that eventually disturb the insulin production in the beta cells indicated by the decreased insulin secretion during postnatal life.

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“…VPA is an anticonvulsant drug with a broad spectrum in the treatment of epilepsy ( 17 ). The use of VPA during pregnancy is known to cause a congenital malformation ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring

et al. 2018

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“…The study found a potential increase in weight and BMI with a significant reduction of height centiles among epileptic patients at six months and one year. On the other hand, no major change was noted regarding serum calcium at any time [60,61] . One study included 209 epileptic children from Iran with a mean age of 7.02 years and was on a low therapeutic dose of VPA mono-therapy found that 53.1% of children gained weight, and decreased appetite was prevalent among 11% of children, and it was significantly common among younger patients.…”

Section: Valproic Acid (Vpa) For the Treatment Of Epilepsy And Associ...mentioning

confidence: 77%

“…However, valproic acid has been linked with various adverse effects and toxicities. It was recommended to use valproic acid with caution in children patients with epilepsy (Maksoud et al 2016) [60,61] . The incidence of side effects is elevated in children patients compared to the adult population due to changes in pharmacokinetic parameters and pharmacodynamic reactions that occur with development throughout childhood (Lee 2019; Sven et al 2016) [53] .…”

Section: Discussionmentioning

confidence: 99%

“…However, the choice of medication can be affected by the side effects of the drug and may be performed in conjunction with a neurologist (Claassen et al, 2015) [17] . Epilepsy requires long-term AED therapy [60,61] . Failure of treatment and poor adherence is very popular among patients experiencing adverse effects of AEDs, and this leads to treatment discontinuation among almost 25% (Perucca et al, 2009;Uijl et al, 2009) [73] .…”

Section: Treatment Of Epilepsy In Childrenmentioning

confidence: 99%

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The Clinical Importance of Total Drug Monitoring in Reducing the Toxicity Associated with Valproic Acid in Epileptic Children in Taif City

Alghamdi¹,

Alghamdi²,

Alsayyali³

et al. 2022

Ijmabhr

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Background: Epilepsy is a group of neurological disorders that are characterized by an epileptic seizure. An epileptic seizure can last for seconds and may last for a longer time of fewer than five minutes. An epileptic seizure may cause physical harm; therefore, its management is necessary. Epilepsy requires long-term epileptic treatment. Children with epilepsy can be managed by valproic acid, which is the very commonly used antiepileptic drug in clinical practice. However, chronic usage of valproic acid is associated with adverse effects, especially among children. These adverse effects involve hepatotoxicity, coagulation disorders, and pancreatitis. Therapeutic drug monitoring (TDM) is effective in adjusting the dosage of the drug to obtain the optimum concentration in order to reduce toxicities associated with the medication. Aim: To investigate the effects of TDM in assessing liver injury associated with valproic acid treatment for epileptic children. Methods: This study is a cohort study that was conducted on epileptic children treated with valproic acid monotherapy at least one month after using TDM at the children hospital in Taif. Liver enzymes, serum creatinine, total bilirubin, direct bilirubin, and dose of valproic acid adjusted by TDM were estimated. Statistical analysis was performed using SPSS software version 21. Results: A total of 126 epileptic children were involved in our study; 68 were involved in the TDM group, and 58 were involved in the non-TDM group. There were significant differences between the two groups regarding the mean of AST (P=0.0001), ALT (P=0.048), and total bilirubin (P=0.0001). There was a significant negative association between valproic acid levels determined by TDM and ALT (r=-0.256, P=0.035), whereas the correlation was positive with serum creatinine (r=0.414, P=0.0001). Logistic regression model showed significant association between TDM usage and elevated AST, OR=0.033, 95% CI=0.004-0.2 (P=0.001). Conclusion: TDM has a significant impact in reducing liver injury and maintaining good hepatic function among epileptic children treated with valproic acid. TDM is also can be used to monitor renal function and correct renal injury by adjusting the valproic acid dose.

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“…Several studies have also shown decreased vitamin D levels in children due to the administration of ASMs, which interfere with children’s height growth [11] , [12] . Height growth is a complex process of chondrocyte proliferation, chondrocyte hypertrophy, and the endochondral ossification of bone growth plates, all of which are influenced by various factors, including vitamin D [13] .…”

Section: Introductionmentioning

confidence: 99%

Comparison of 25-hydroxy vitamin D serum levels among children with epilepsy in therapy with single versus multiple antiseizure medications

Indra Gunawan,

Rochmah,

Faizi

2023

Epilepsy & Behavior Reports

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Effect of antiepileptic drug (valproic acid) on children growth

Cited by 4 publications

References 26 publications

Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring

Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring

The Clinical Importance of Total Drug Monitoring in Reducing the Toxicity Associated with Valproic Acid in Epileptic Children in Taif City

Comparison of 25-hydroxy vitamin D serum levels among children with epilepsy in therapy with single versus multiple antiseizure medications

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