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Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications ( ASM)) are a diverse group of pharmacological agents used in the treatment of epilepsy . Anticonvulsants are also used in the treatment of bipolar disorder and borderline personality disorder,American Psychiatric Association, and American Psychiatric Association. Work Group on Borderline Personality Disorder. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Pub, 2001. since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the uncontrolled and excessive firing of during seizures and in doing so can also prevent the spread of the seizure within the brain.
Conventional antiepileptic drugs have diverse mechanisms of action but many block or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptor, the GABA transporter type 1, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calcium channels, antiepileptic drugs reduce the release of the excitatory neurotransimtter glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA. This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act pro-convulsively. Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.
Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent the development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown in human trials to prevent epileptogenesis (the development of epilepsy in an individual at risk, such as after a head injury).
Many anticonvulsants are known Teratology and increase the risk of birth defects in the unborn child if taken while pregnant.
The following benzodiazepines are used to treat status epilepticus:
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.
Vigabatrin and progabide are also analogs of GABA.
Gabapentinoids are analogs of GABA, but they do not act on GABA receptors. They have analgesic, anticonvulsant, and anxiolytic effects.
| acetazolamide | Diamox | 27 July 1953 | 1988 Epilepsy Action: Druglist. Retrieved on 1 November 2007. | |
| brivaracetam | Briviact | 18 February 2016 | ||
| carbamazepine | Tegretol | 15 July 1974 (Initial approval on 11 March 1968 was for trigeminal neuralgia.) | 1965 | 1963 |
| cenobamate | Xcopri | 21 November 2019 | ||
| clobazam | Onfi/Frisium | 21 October 2011 | 1979 | |
| clonazepam | Klonopin/Rivotril | 4 June 1975 | 1974 | |
| diazepam | Valium | 15 November 1963 | ||
| divalproex sodium | Depakote | 10 March 1983 | ||
| eslicarbazepine | Aptiom | 11 August 2013 | ||
| ethosuximide | Zarontin | 2 November 1960 | 1955 | 1962 |
| ethotoin | Peganone | 22 April 1957 | ||
| everolimus | Afinitor/Votubia | 30 January 2009 | ||
| felbamate | Felbatol | 29 July 1993 | ||
| fosphenytoin | Cerebyx | 5 August 1996 | ||
| gabapentin | Neurontin | 30 December 1993 | May 1993 | October 1994 |
| lacosamide | Vimpat | 28 October 2008 | ||
| lamotrigine | Lamictal | 27 December 1994 | October 1991 | May 1995 |
| levetiracetam | Keppra | 30 November 1999 | 29 September 2000 EPAR: Keppra. Retrieved on 1 November 2007. | 29 September 2000 |
| mephenytoin | Mesantoin | 23 October 1946 | ||
| metharbital | Gemonil | 1952 (2025). 9780632060467, Blackwell Science. ISBN 9780632060467 | ||
| methsuximide | Celontin | 8 February 1957 | ||
| methazolamide | Neptazane | 26 January 1959 | ||
| oxcarbazepine | Trileptal | 14 January 2000 | 2000 | |
| phenobarbital | Luminal | Unknown | 1912 | 1920 |
| phenytoin | Dilantin/Epanutin | 1938 (Marketed in 1938, approved 1953) | 1938 | 1941 |
| piracetam | Nootropil | never approved | ||
| phensuximide | Milontin | 1953 (1992). 9780824785499, Dekker. ISBN 9780824785499 (first usage) | ||
| pregabalin | Lyrica | 30 December 2004 | 6 July 2004 EPAR: Lyrica Retrieved on 1 November 2007. | 6 July 2004 |
| primidone | Mysoline | 8 March 1954 | 1952 | 1953 |
| rufinamide | Banzel/Inovelon | 14 November 2008 | ||
| sodium valproate | Epilim | Unknown | December 1977 | June 1967 |
| stiripentol | Diacomit | 20 August 2018 | January 2007 | January 2007 |
| tiagabine | Gabitril | 30 September 1997 | 1998 | November 1997 |
| topiramate | Topamax | 24 December 1996 | 1995 | |
| trimethadione | Tridione | 25 January 1946 | ||
| valproic acid | Depakene/Convulex | 28 February 1978 | 1993 | |
| vigabatrin | Sabril | 21 August 2009 | 1989 | |
| zonisamide | Zonegran | 27 March 2000 | 10 March 2005 EPAR: Zonegran. Retrieved on 1 November 2007 | 10 March 2005 |
Valproic acid, and its derivatives such as sodium valproate and divalproex sodium, causes cognitive deficit in the child, with an increased dose causing decreased intelligence quotient and use is associated with adverse neurodevelopmental outcomes (cognitive and behavioral) in children. On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure. Similarly, children exposed lamotrigine or phenytoin in the womb do not seem to differ in their skills compared to those who were exposed to carbamazepine.
There is inadequate evidence to determine if newborns of women with epilepsy taking anticonvulsants have a substantially increased risk of hemorrhagic disease of the newborn.
There is little evidence to suggest that anticonvulsant/ASM exposure through breastmilk has clinical effects on newborns. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study showed that most blood concentrations in breastfed infants of mothers taking carbamazepine, oxcarbazepine, valproate, levetiracetam, and topiramate were quite low, especially in relationship to the mother's level and what the fetal level would have been during pregnancy. (Note: valproic acid is NOT a recommended ASM for people with epilepsy who are considering having children.)
Infant exposure to newer ASMs (cenobamate, perampanel, brivaracetam, eslicarbazepine, rufinamide, levetiracetam, topiramate, gabapentin, oxcarbazepine, lamotrigine, and vigabatrin) via breastmilk was not associated with negative neurodevelopment (such as lower IQ and autism spectrum disorder) at 36 months.
Several studies that followed children exposed to ASMs during pregnancy showed that a number of widely used ones (including lamotrigine and levetiracetam) carried a low risk of adverse neurodevelopmental outcomes (cognitive and behavioral) in children when compared to children born to mothers without epilepsy and children born to mothers taking other anti-seizure medications. Data from several pregnancy registries showed that children exposed to levetiracetam or lamotrigine during pregnancy had the lowest risk of developing major congenital malformations compared to those exposed to other ASMs. The risk of major congenital malformations for children exposed to these ASMs were within the range for children who were not exposed to any ASMs during pregnancy.
People with epilepsy can have healthy pregnancies and healthy babies. However, proper planning and care is essential to minimize the risk of congenital malformations or adverse neurocognitive outcomes for the fetus while maintaining seizure control for the pregnant person with epilepsy. If possible, when planning pregnancy, people with epilepsy should switch to ASMs with the lowest teratogenic risk for major congenital malformations as well as the least risk of adverse neurodevelopmental outcomes (e.g., lower IQ or autism spectrum disorder). They should also work with their healthcare providers to identify the lowest effective ASM dosage that will maintain their seizure control while regularly checking medication levels throughout pregnancy.
Data from studies conducted on women taking antiepileptic drugs for non-epileptic reasons, including depression and bipolar disorder, show that if high doses of the drugs are taken during the first trimester of pregnancy then there is the potential of an increased risk of congenital malformations.
Research
The mechanism of how anticonvulsants cause birth defects is not entirely clear. During pregnancy, the metabolism of many anticonvulsants is affected. There may be an increase in the clearance and resultant decrease in the blood concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. In animal models, several anticonvulsant drugs have been demonstrated to induce neuronal apoptosis in the developing brain.
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