Article

Serum lipids in epileptic children treated with carbamazepine and valproate.

Bakirköy State Hospital for Neurological and Psychiatric Diseases, Department of Neurology, Istanbul, Turkey.
European Journal of Pediatrics (impact factor: 1.88). 08/1997; 156(7):565-7. DOI:10.1007/s004310050664 pp.565-7
Source: PubMed

ABSTRACT Serum total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol, triglyceride, apolipoproteins A1 and B levels were studied in 57 healthy children and in 39 children with epilepsy who had been receiving carbamazepine (CBZ) (23 children) for 1.58 +/- 1.10 years or valproic acid (VPA) (16 children) for 1.34 +/- 1.11 years. In patients receiving CBZ, mean TC level, mean LDL-C level, mean TC/HDL-C ratio and mean LDL-C/HDL-C ratio-were significantly higher than controls. None of the mean levels of serum lipids evaluated in patients receiving VPA was significantly different from the corresponding control group mean. Changes in serum lipids correlated with neither duration of therapy or plasma antiepileptic levels nor age or gender. CONCLUSION: Our results suggested that CBZ, a hepaticenzyme-inducing drug, affects serum lipid status. Long-term prospective studies are necessary to determine whether chronic CBZ therapy is a risk factor for atherosclerotic disorders.

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    Article: Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults.
    Susanne Brämswig, Anja Kerksiek, Thomas Sudhop, Claus Luers, Klaus Von Bergmann, Heiner K Berthold
    [show abstract] [hide abstract]
    ABSTRACT: Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects of CBZ on lipid metabolism in normolipemic adults. In 21 healthy males, lipoprotein and noncholesterol sterol concentrations were measured before and during treatment with CBZ for 70 +/- 18 days. Thirteen subjects underwent kinetic studies of apolipoprotein-B (ApoB) metabolism with the use of endogenous stable isotope labeling. Lipoprotein kinetic parameters were calculated by multicompartmental modeling. Significant increases in total cholesterol, in ApoB-containing lipoproteins [very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low-density lipoprotein (LDL)], and in triglycerides, but not in high-density lipoprotein (HDL), were observed. Lipoprotein particle composition remained unchanged. Mean fractional catabolic and production rates of ApoB-containing lipoproteins were not significantly different, although mean production rates of VLDL and IDL were substantially increased (+46 +/- 139% and +30 +/- 97%, respectively), whereas mean production of LDL remained unchanged (+2.1 +/- 45.6%). Cholestanol in serum increased significantly but not the concentrations of plant sterols (campesterol, sitosterol) and the cholesterol precursors (lathosterol, mevalonic acid). There was a significant correlation between the decrease in free thyroxine and the increase in IDL cholesterol. Treatment with CBZ increases mainly ApoB-containing lipoproteins. CBZ seems not to influence endogenous cholesterol synthesis or intestinal absorption directly. The increase is neither related to increased ApoB production nor to decreased catabolism but is rather due to changes in the conversion cascade of IDL particles, most likely as an indirect effect through a decrease in thyroid hormones.
    AJP Heart and Circulatory Physiology 03/2002; 282(2):H704-16. · 3.71 Impact Factor
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    Article: Atherosclerotic risk among children taking antiepileptic drugs.
    Tomasz Jakubus, Małgorzata Michalska-Jakubus, Krzysztof Lukawski, Agnieszka Janowska, Stanisław J Czuczwar
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    ABSTRACT: Epilepsy is a common chronic neurological disorder that requires long-term or sometimes lifetime therapy. Recent evidence indicates that prolonged use of antiepileptic drugs (AEDs) might modify some vascular risk factors; however, the influence of AED therapy on the development of atherosclerosis has been the subject of controversy. Some epidemiological studies have reported a higher prevalence of ischemic vascular disease among epileptic patients on AEDs, while in other studies the mortality due to atherosclerosis-related cardiovascular disease in treated epileptics has been observed to be lower than in the general population. The etiology of atherosclerosis-related vascular diseases in epileptic patients has not been fully clarified. Since atherosclerotic vascular alterations may start early in life, this review focuses on major atherogenic risk factors among epileptic children, including altered metabolism of homocysteine, disordered lipid profiles, and increased lipoprotein (a) serum levels, as well as thyroid hormone deficiency with special concern for clinical implications.
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    Article: Relationship between antiepileptic drugs and biological markers affecting long-term cardiovascular function in children and adolescents.
    Laura S Cheng, Asuri N Prasad, Michael J Rieder
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    ABSTRACT: Epilepsy is a neurological disorder, relatively common in the paediatric population. These children are often treated with antiepileptic drugs (AEDs) for several years. The consequence of such long-term exposure may lead to variations in plasma homocysteine and serum lipoprotein concentrations. To review the cardiovascular effects of anticonvulsant therapy and their use in childhood epilepsy with special reference to homocysteine and lipoprotein. A literature search was conducted on PubMed (1966-May 2009) and MEDLINE (1966-May 2009). Key terms included antiepileptic drugs, epilepsy, homocysteine, cardiovascular events, and children. Certain AEDs including carbamazepine, phenobarbital, phenytoin and valproic acid, as well as the presence of a homozygous 5-methylenetetrahydrofolate reductase polymorphism in the genotype, are potential causes of elevation in plasma homocysteine and serum lipoprotein concentrations. Persistent elevation in these biochemical markers has shown to be associated with the development of long-term sequelae such as cardiovascular diseases, prompting concerns about the long-term implications of chronic AED use in children and cardiovascular risk. Further research is needed to assess the relationship between specific chronic AED use, homocysteine and lipoprotein concentrations, the influence of genotype, as well as the risk of long-term sequelae in the paediatric population.
    The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique 01/2010; 17(1):e5-46.
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Keywords

39 children
 
57 healthy children
 
apolipoproteins A1
 
atherosclerotic disorders
 
B levels
 
corresponding control group
 
hepaticenzyme-inducing drug
 
high-density lipoprotein
 
Long-term prospective studies
 
low-density lipoprotein
 
low-density lipoprotein cholesterol
 
mean levels
 
plasma antiepileptic levels
 
serum lipid status
 
serum lipids
 
serum lipids correlated
 
Serum total cholesterol
 
TC/HDL-C ratio
 
valproic acid
 
VPA
 

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