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anticonvulsant

 
Dictionary: an·ti·con·vul·sant   (ăn'tē-kən-vŭl'sənt, ăn'tī-) pronunciation
n.

A drug that prevents or relieves convulsions.

anticonvulsive an'ti·con·vul'sive (-sĭv) adj.

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Neurological Disorder:

Anticonvulsants

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Definition

Anticonvulsants are a class of drugs indicated for the treatment of various types of seizures associated with seizure disorders such as epilepsy, a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain, and other disorders.

Some anticonvulsants are indicated for other medical uses. Some hydantoins, such as phenytoin, are also used as skeletal muscle relaxants and antineuralgics in the treatment of neurogenic pain. Some anticonvulsants and antiepileptic drugs (AEDs) are used in psychiatry for the treatment of bipolar disorders (manic-depression).

Purpose

Although there is no cure for the disorder, anticonvulsants are often effective in controlling the seizures associated with epilepsy. The precise mechanisms by which many anticonvulsants work are unknown, and different sub-classes of anticonvulsants are thought to exert their therapeutic effects in diverse ways. Some anticonvulsants are thought to generally depress central nervous system (CNS) function. Others, such as GABA inhibitors, are thought to target specific neurochemical processes, suppress excess neuron function, and regulate electrochemical signals in the brain.

Description

There are several sub-classes and types of anticonvulsants. They are marketed in the United States under a variety of brand names.

  • Barbiturates, including Mephobarbital (Mebaral), Pentobarbital (Nembutal), and Phenobarbital (Luminol, Solfoton).
  • Benzodiazepines, including Chlorazepate (Tranxene), Clonazepam (Klonopin), and Diazepam (Valium).
  • GABA Analogues, including Gabapentin (Neurontin) and Tiagabine (Gabitril).
  • Hydantoins, including Ethotoin (Peganone), Fosphentyoin (Mesantoin), and Phenytoin (Dilantin).
  • Oxazolidinediones, including Trimethadione (Tridione).
  • Phenyltriazines, including Lamotrigine (Lamictal).
  • Succinamides, including Ethosuximide (Zarontin), Methsuximide (Celontin), and Phensuximide (Milontin).
  • Other anticonvulsants, including Acetazolamide (Diamox), Carbamazepine (Carbatrol, Tegretol), Felbamate (Felbatol), Levetiracetam (Keppra), Oxcarbazepine (Trileptal), Primidone (Mysoline), Topiramate (Topamax), Valproic acid (Depakene, Depakote), and Zonisamide (Zonegran).

A physician prescribes anticonvulsant medication, or a combination of anticonvulsant medications, according to seizure type and pattern in individual patients. Some anti-convulsant medications are not appropriate for pediatric patients under 16 years of age.

Recommended dosage

Anticonvulsants are available in oral suspension (syrup), injectable, capsule, tablet, and sprinkle forms, depending on the type of medication. Not all anticonvulsants will be available in all forms. Anticonvulsants are prescribed by physicians in varying daily dosages, depending on the age, weight, and other health concerns of the individual patient, as well as the severity and frequency of their seizures.

It is important to follow the prescribing physicians directions carefully as each individual anticonvulsant medication has its own recommended daily dosages and dose schedule. Some anticonvulsants are taken in a single daily dose; others are taken in divided, multiple daily doses. A double dose of any anticonvulsant medication should not be taken. If a dose is missed, it should be taken as soon as possible. However, if it is within four hours of the next scheduled dose, the missed dose should be skipped. Taking an anticonvulsant at regular intervals and at the same time each day enables consistent levels of the medication to be maintained in the bloodstream, and results in more effective seizure control.

In general, initiating any course of treatment which includes anticonvulsants requires a gradual dose-increasing regimen. Adults and children typically take a smaller daily dose for the first two weeks. Daily dosages of anti-convulsant medication may then be slowly titrated, or increased over time until adequate seizure control is achieved using the lowest dose possible.

When ending a course of treatment of anticonvulsant, physicians typically taper the patient's daily dose over a period of several weeks. Suddenly stopping treatment including anticonvulsants may cause seizures to return or occur with greater frequency. Patients taking anticonvulsants drugs for the treatment of pain or bipolar disorders may experience also have seizures, even if they have never had them before, if they suddenly stop taking the medication.

Precautions

Each anticonvulsant medication may have its own precautions, counter-indications, and side-effects. However, many are common to all anticonvulsant medications.

Consult the prescribing physician before taking any anticonvulsant with non-perscription medications. Patients should avoid alcohol and CNS depressants (medications that make one drowsy or tired, such as antihistimines, sleep medications, and some pain medications) while taking anticonvulants. Anticonvulsants can exacerbate the side effects of alcohol and other medications. Alcohol may also increase the risk or frequency of seizures.

Anticonvulsants may not be suitable for persons with a history of stroke, anemia, thyroid, liver, depressed kidney function, diabetes mellitus, severe gastro-intestional disorders, porphyria, lupus, some forms of mental illness, high blood presure, angina (chest pain), irregular heartbeats, and other heart problems.

Before beginning treatment with anticonvulsants, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are nursing, pregnant, or plan to become pregnant.

Physicians generally advise the use of effective birth control while taking many anticonvulsant medications. Patients taking anticonvulsants should be aware that many anticonvulsants may increase the risk of birth defects. Furthermore, many anticonvulsant medications are secreted in breast milk. Patients who become pregnant while taking any anticonvulsant should contact their physician immediately to discuss the risks and benefits of continuing treatment during pregnancy and while nursing.

Some anticonvulsants may be prescribed for children. However, children may experience increased side effects. Research indicates that some children who take high doses of some anticonvulsants (such as hydantoins) for an extended period of time may experience mild learning difficulties or not perform as well in school.

Side effects

In some patients, anticonvulsants may produce usually mild side effects. Headache, nausea, and unusual tiredness and weakness are the most frequently reported side effects of anticonvulsants. Other general side effects of anticonvulsants that do not usually require medical attention include:

  • mild coordination problems
  • mild dizziness
  • abdominal pain or cramping
  • sinus pain
  • sleeplessness or nightmares
  • change in appetite
  • mild feelings of anxiety
  • feeling of warmth
  • tingling or prickly feeing on the skin, or in the toes and fingers
  • mild tremors
  • diarrhea or constipation
  • heartburn or indigestion
  • aching joints and muscles or chills
  • unpleasant taste in mouth or dry mouth

Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication. However, if any symptoms persist or become too uncomfortable, the perscribing physician should be consulted.

Other, uncommon side effects of anticonvulsants can be serious or may indicate an allergic reaction. A patient taking any anticonvulsant who experiencs one or more of the following symptoms should contact the prescribing physician immediately:

  • rash or bluish, purplish, or white patches on the skin
  • jaundice (yellowing of the skin and eyes)
  • bloody nose or unusual bleeding
  • hallucinations (seeing visions or hearing voices that are not present)
  • sores in the mouth or around the eyes
  • ringing or vibrations in the ears
  • depression or suicidal thoughts
  • mood or mental changes, including excessive fear, anxiety, hostility
  • severe tremors
  • prolonged numbness in the extremeties
  • general loss of motor skills
  • persistent lack of appetite
  • altered vision
  • frequent or burning urination
  • difficulty breathing
  • chest pain or irregular heartbeat
  • faintness or loss of consciousness
  • persistant, severe headaches
  • persistant fever or pain.

Interactions

Anticonvulsants may have negative interactions with some antacids, anticoagulants, antihistimines, antidepressants, antibiotics, pain killers (including lidocaine) and monoamine oxidase inhibitors (MAOIs). Other medications such as amiodarone, diazoxide, phenybutazone, sulfonamides (sulfa drugs), corticosteroids, sucralfate, rifampin, and warfarin may also adversely react with anti-convulsants.

Some anticonvulsants should not be used in combination with other anticonvulsants. (For example, phenytoin (a hydantoin) when used with valproic acid, another anticonvulsant, may increase the seizure frequency). However, several anticonvulsant medications are indicated to be used in conjunction with or suppliment other anti-convulsants. If advised and carefully monitored by a physician, a course of treatment including multiple seizure prevention medications can be effective and safe.

Most anticonvulsants decrease the effectiveness of contraceptives that contain estrogens or progestins, including oral contraceptives (birth control pills), progesterone implants (Norplant), and progesterone injections (Depo-Provera).

Resources

BOOKS

Masters, Roger D., Michael T. McGuire. The Neurotransmitter Revolution. Southern Illinois University Press, 1994.

Mondimore, Francis Mark. Bipolar Disorder: A Guide for Patients and Families. Baltimore: The Johns Hopkins University Press, 1999.

Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Firefly Books, 2001.

Wyllie, Elaine. The Treatment of Epilepsy: Principles and Practice. New York: Lippincott, Williams & Wilkins, 2001.

PERIODICALS

Feely, Morgan. "Drug treatment of epilepsy." BMJ 318 (9 January 1999): 106–109.

"Risk of birth defects with anticonvulsants evaluated." Psychopharmacology Update 12, no. 5 (May 2001): 3.

OTHER

"Seizure Medicines." Epilepsy.com.http://www.epilepsy.com/epilepsy/seizure_medicines.html (May 1, 2004).

ORGANIZATIONS

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. http://www.aesnet.org.


Adrienne Wilmoth Lerner


Dental Dictionary: anticonvulsive
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(an′tīkōnvul′siv)
adj

Relieving or preventing convulsion.

Veterinary Dictionary: anticonvulsant
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1. inhibiting convulsions. Any drug that depresses the central nervous system may be used for its anticonvulsant effect. This includes narcotics and sedatives. They have the undesirable effect of depressing all CNS functions.
2. a specific motor depressant, such as anticonvulsant or antiepileptic, which depresses specifically the motor centers and suppresses spontaneous motor activity; examples are phenobarbital, phenytoin, primidone and diazepam.

Wikipedia: Anticonvulsant
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The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure. Because of this, anticonvulsants also have proven effective in treating many kinds of dysfunctional anxiety. Failing this, an effective anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic effects that may result in brain damage. However, anticonvulsants themselves have been linked to lowered IQ in children.[1] Anticonvulsants are often called antiepileptic drugs (abbreviated "AEDs") or antiseizure drugs (abbreviated "ASDs").

The major molecular targets of marketed anticonvulsant drugs are 1) voltage-gated sodium channels; 2) components of the GABA system, including GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase; and 3) voltage-gated calcium channels.[2]

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent the expected development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown to prevent epileptogenesis (the development of epilepsy after an injury such as a head injury) in human trials.[3]

Contents

Approval

The usual method of achieving approval for a drug is to show it is effective when compared against placebo, or that it is more effective than an existing drug. In monotherapy (where only one drug is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is currently uncontrolled by their medication (i.e., it is refractory to treatment) are selected to see if supplementing the medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo.[3]

Once there is confidence that a drug is likely to be effective in monotherapy, trials are conducted where the drug is compared to an existing standard. For partial-onset seizures, this is typically carbamazepine. Despite the launch of over ten drugs since 1990, no new drug has been shown to be more effective than the older set, which includes carbamazepine, valproate and phenytoin. The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earned FDA approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments, and has approved many more. Despite their lack of FDA approval, the American Academy of Neurology and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy.[3]

Drugs

In the following list, the dates in parentheses are the earliest approved use of the drug.

Aldehydes

Main article: Aldehydes

  • Paraldehyde (1882). One of the earliest anticonvulsants. Still used to treat status epilepticus, particularly where there are no resuscitation facilities.

Aromatic allylic alcohols

  • Stiripentol (2001 - limited availability). Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI).

Barbiturates

Main article: Barbiturates

Barbiturates are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. The following are classified as anticonvulsants:

Phenobarbital was the main anticonvulsant from 1912 till the development of phenytoin in 1938. Today, phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first. Other barbiturates only have an anticonvulsant effect at anaesthetic doses.

Benzodiazepines

Main article: Benzodiazepines

The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant properties. Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance to the anticonvulsant effects and dependency.[4][5][6][7] Of the many drugs in this class, only a few are used to treat epilepsy:

  • Clobazam (1979). Notably used on a short-term basis around menstruation in women with catamenial epilepsy.
  • Clonazepam (1974).
  • Clorazepate (1972).

The following benzodiazepines are used to treat status epilepticus:

  • Diazepam (1963). Can be given rectally by trained care-givers.
  • Midazolam (N/A). Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa.
  • Lorazepam (1972). Given by injection in hospital.

Nitrazepam, temazepam, and especially nimetazepam are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties.

Bromides

Main article: Bromides

  • Potassium bromide (1857). The earliest effective treatment for epilepsy. There would not be a better drug for epilepsy until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

Carbamates

Main article: Carbamates

  • Felbamate (1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

Carboxamides

Carbamazepine

Main article: Carboxamides

The following are carboxamides:

  • Carbamazepine (1963). A popular anticonvulsant that is available in generic formulations.
  • Oxcarbazepine (1990). A derivative of carbamazepine that has similar efficacy but is better tolerated.

Fatty acids

Main article: Fatty acids

The following are fatty-acids:

Vigabatrin and progabide are also analogs of GABA.

Fructose derivatives

Gaba analogs

Hydantoins

Main article: Hydantoins

The following are hydantoins:

Oxazolidinediones

Main article: Oxazolidinediones

The following are oxazolidinediones:

Propionates

Main article: Propionates

Pyrimidinediones

Main article: Pyrimidinediones

Pyrrolidines

Main article: Pyrrolidines

Succinimides

Main article: Succinimides

The following are succinimides:

Sulfonamides

Main article: Sulfonamides

Triazines

Main article: Triazines

Ureas

Main article: Ureas

Valproylamides (amide derivatives of valproate)

Main article: Amides

Diet

The ketogenic diet is a strict medically supervised diet that has an anticonvulsant effect. It is typically used in children with refractory epilepsy.

Devices

The vagus nerve stimulator (VNS) is a device that sends electric impulses to the left vagus nerve in the neck via a lead implanted under the skin. It was FDA approved in 1997 as an adjunctive therapy for partial-onset epilepsy.

Marketing approval history

The following table lists anticonvulsant drugs together with the date their marketing was approved in the US, UK and France. Data for the UK and France are incomplete. In recent years, the European Medicines Agency has approved drugs throughout the European Union. Some of the drugs are no longer marketed.

Drug Brand US UK France
acetazolamide Diamox 1953-07-271953-07-27[8] 1988[9]
carbamazepine Tegretol 1974-07-151974-07-15[10][11] 1965[9] 1963[12]
clobazam Frisium 1979[9]
clonazepam Klonopin/Rivotril 1975-06-041975-06-04[13] 1974[9]
diazepam Valium 1963-11-151963-11-15[14]
divalproex sodium Depakote 1983-03-101983-03-10[15]
ethosuximide Zarontin 1960-11-021960-11-02[16] 1955[9] 1962[12]
ethotoin Peganone 1957-04-221957-04-22[17]
felbamate Felbatol 1993-07-291993-07-29[18]
fosphenytoin Cerebyx 1996-08-051996-08-05[19]
gabapentin Neurontin 1993-12-301993-12-30[20] 1993-05May 1993[9][12] 1994-10October 1994[12]
lamotrigine Lamictal 1994-12-271994-12-27[21] 1991-10October 1991[9][12] 1995-05May 1995[12]
levetiracetam Keppra 1999-11-301999-11-30[22] 2000-09-292000-09-29[9][23] 2000-09-292000-09-29[23]
mephenytoin Mesantoin 1946-10-231946-10-23[24]
metharbital Gemonil 1952[25][26]
methsuximide Celontin 1957-02-081957-02-08[27]
methazolamide Neptazane 1959-01-261959-01-26[28]
oxcarbazepine Trileptal 2000-01-142000-01-14[29] 2000[9]
phenobarbital 1912[9] 1920[12]
phenytoin Dilantin/Epanutin 1938[30][12] 1938[9] 1941[12]
phensuximide Milontin 1953[31][32]
pregabalin Lyrica 2004-12-302004-12-30[33] 2004-07-062004-07-06[9][34] 2004-07-062004-07-06[34]
primidone Mysoline 1954-03-081954-03-08[35] 1952[9] 1953[12]
sodium valproate Epilim 1977-12December 1977[12] 1967-06June 1967[12]
stiripentol Diacomit 2001-12-052001-12-05[36] 2001-12-052001-12-05[36]
tiagabine Gabitril 1997-09-301997-09-30[37] 1998[9] 1997-11November 1997[12]
topiramate Topamax 1996-12-241996-12-24[38] 1995[9]
trimethadione Tridione 1946-01-251946-01-25[39]
valproic acid Depakene/Convulex 1978-02-281978-02-28[40] 1993[9]
vigabatrin Sabril 1989[9]
zonisamide Zonegran 2000-03-272000-03-27[41] 2005-03-102005-03-10[9][42] 2005-03-102005-03-10[42]

See also

References

  1. ^ Loring, David W (2005-09-01). "Cognitive Side Effects of Antiepileptic Drugs in Children". Psychiatric Times XXII (10). http://www.psychiatrictimes.com/showArticle.jhtml?articleID=171201519. 
  2. ^ Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004 Jul;5(7):553-564. PMID 15208697
  3. ^ a b c Abou-Khalil BW (2007). "Comparative monotherapy trials and the clinical treatment of epilepsy". Epilepsy currents / American Epilepsy Society 7 (5): 127–9. doi:10.1111/j.1535-7511.2007.00198.x. PMID 17998971. 
  4. ^ Browne TR (May 1976). "Clonazepam. A review of a new anticonvulsant drug". Arch Neurol 33 (5): 326–32. PMID 817697. 
  5. ^ Isojärvi, JI; Tokola RA (December 1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability". J Intellect Disabil Res 42 (1): 80–92. PMID 10030438. 
  6. ^ Tomson T; Svanborg E, Wedlund JE (May-Jun 1986). "Nonconvulsive status epilepticus: high incidence of complex partial status". Epilepsia 27 (3): 276–85. doi:10.1111/j.1528-1157.1986.tb03540.x. PMID 3698940. 
  7. ^ Djurić, M; Marjanović B, Zamurović D (May-Jun 2001). "[West syndrome--new therapeutic approach]". Srp Arh Celok Lek 129 (1): 72–7. PMID 15637997. 
  8. ^ NDA 008943
  9. ^ a b c d e f g h i j k l m n o p q r Epilepsy Action: Druglist. Retrieved on 2007-11-01.
  10. ^ NDA 016608 (Initial approval on 1968-03-11 was for trigeminal neuralgia.)
  11. ^ Schain, Richard J. (01 March 1978). "Pediatrics—Epitomes of Progress: Carbamazepine (Tegretol) in the Treatment of Epilepsy". Western Journal of Medicine 128 (3): 231–232. PMID 18748164. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1238063. Retrieved 2007-03-14. 
  12. ^ a b c d e f g h i j k l m Loiseau, Pierre Jean-Marie (June 1999). "Clinical Experience with New Antiepileptic Drugs: Antiepileptic Drugs in Europe" (PDF). Epilepsia 40 (Suppl 6): S3–8. doi:10.1111/j.1528-1157.1999.tb00925.x. PMID 10530675. http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1528-1157.1999.tb00925.x. Retrieved 2007-03-26. 
  13. ^ NDA 017533
  14. ^ NDA 013263
  15. ^ NDA 018723
  16. ^ NDA 012380
  17. ^ NDA 010841
  18. ^ NDA 020189
  19. ^ NDA 020450
  20. ^ NDA 020235
  21. ^ NDA 020241
  22. ^ NDA 021035
  23. ^ a b EPAR: Keppra. Retrieved on 2007-11-01.
  24. ^ NDA 006008
  25. ^ NDA 008322
  26. ^ Dodson, W. Edwin; Giuliano Avanzini; Shorvon, Simon D.; Fish, David R.; Emilio Perucca (2004). The treatment of epilepsy. Oxford: Blackwell Science. xxviii. ISBN 0-632-06046-8. 
  27. ^ NDA 010596
  28. ^ NDA 011721
  29. ^ NDA 021014
  30. ^ NDA 008762 (Marketed in 1938, approved 1953)
  31. ^ NDA 008855
  32. ^ Kutt, Henn; Resor, Stanley R. (1992). The Medical treatment of epilepsy. New York: Dekker. pp. 385. ISBN 0-8247-8549-5.  (first usage)
  33. ^ NDA 021446
  34. ^ a b EPAR: Lyrica Retrieved on 2007-11-01.
  35. ^ NDA 009170
  36. ^ a b EPAR: Diacomit. Orphan designation: 2001-12-05, full authorisation: 2007-01-04 Retrieved on 2007-11-01.
  37. ^ NDA 020646
  38. ^ NDA 020505
  39. ^ NDA 005856
  40. ^ NDA 018081
  41. ^ NDA 020789
  42. ^ a b EPAR: Zonegran. Retrieved on 2007-11-01

External links


 
 

 

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Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved.  Read more
Neurological Disorder. Gale Encyclopedia of Neurological Disorders. Copyright © 2005 by The Gale Group, Inc. All rights reserved.  Read more
Dental Dictionary. Mosby's Dental Dictionary. Copyright © 2004 by Elsevier, Inc. All rights reserved.  Read more
Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.  Read more
Wikipedia. This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article "Anticonvulsant" Read more