Neuronal Ceroid Lipofuscinoses Medication

  • Author: Celia H Chang, MD; Chief Editor: Amy Kao, MD   more...
 
Updated: Sep 17, 2009
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

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Anticonvulsants

Class Summary

These agents are used to terminate clinical and electrical seizure activity as rapidly as possible, and to prevent seizure recurrence.

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Carbamazepine (Tegretol)

 

Effective for treatment of complex partial seizures. Appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Major mechanism of action is to reduce sustained high-frequency repetitive neural firing.

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Phenytoin (Dilantin)

 

Primary site of action of hydantoins, such as phenytoin, appears to be motor cortex, where it may inhibit spread of seizure activity. May reduce maximal activity of brain stem centers responsible for tonic phase of grand mal seizures.

Dose should be individualized. If daily dosage cannot be divided equally, larger dose should be given before retiring. Phosphorylated formulation, fosphenytoin, available for parenteral use and may be given IM or IV.

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Valproic acid (Depakote, Depakene, Depacon)

 

Chemically unrelated to other drugs used to treat seizure disorders. Although mechanism of action not established, activity may be related to increased brain levels of GABA, or enhanced GABA action. Valproate may potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect.

For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 wk. This reduction may be started at initiation of therapy or delayed by 1-2 wk if concern that seizures are likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency.

As adjunctive therapy, divalproex sodium may be added to patient's regimen at dosage of 10-15 mg/kg/d.

Dosage may be increased by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses < 60 mg/kg/d.

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Gabapentin (Neurontin)

 

Has properties in common with other anticonvulsants. However, exact mechanism of action not known. Structurally related to GABA but does not interact with GABA receptors.

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Lamotrigine (Lamictal)

 

Triazine derivative useful in treatment of both seizures and neuralgic pain. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. Follow manufacturer's recommendation for dose adjustments.

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Topiramate (Topamax)

 

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel–blocking action, potentiates inhibitory activity of neurotransmitter GABA. In addition, may block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy. On occasion, addition of topiramate to phenytoin may require adjustment of phenytoin dose to achieve optimal clinical outcome.

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Tiagabine (Gabitril)

 

Mechanism of antiseizure effect unknown. However, believed to be related to its ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells and possibly prevents propagation of neural impulses that contribute to seizures by GABAergic action. Modification of concomitant AEDs not necessary, unless clinically indicated.

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Felbamate (Felbatol)

 

Oral antiepileptic agent with weak inhibitory effects on GABA-receptor binding and benzodiazepine receptor binding but interacts as antagonist at strychnine-insensitive glycine recognition site of NMDA receptor-ionophore complex. Not indicated as first-line antiepileptic treatment.

Recommended for use only in those patients whose epilepsy is so severe that benefits outweigh risks of aplastic anemia or liver failure.

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Phenobarbital (Luminal)

 

Exhibits anticonvulsant activity in anesthetic doses and can be administered orally. If IM route chosen, inject into one of large muscles such as gluteus maximus, vastus lateralis, or other areas where little risk of encountering nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurological deficit. Restrict IV use to conditions in which other routes not feasible, either because patient unconscious, as in cerebral hemorrhage, eclampsia, or status epilepticus, or because prompt action imperative.

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Oxcarbazepine (Trileptal)

 

Pharmacologic activity primarily by 10-monohydroxy metabolite (MHD). May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Anticonvulsant effect may occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics similar in older children (>8 y) and adults. Young children ( < 8 y) have 30-40% increased clearance compared with older children and adults. Children < 2 years of age have not been studied in controlled clinical trials.

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Contributor Information and Disclosures
Author

Celia H Chang, MD  Associate Health Sciences Clinical Professor, Department of Neurology, University of California at Davis

Celia H Chang, MD is a member of the following medical societies: American Academy of Neurology and Child Neurology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Beth A Pletcher, MD  Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey

Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Kenneth J Mack, MD, PhD  Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience

Disclosure: Nothing to disclose.

,  Kathy Roarty Placeholder

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD  Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

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