- adj.
- 抗痙攣の、抗けいれんの
- n.
- 関
- anticonvulsant agent、anticonvulsant drug、anticonvulsants、anticonvulsive、antiseizure、antiseizure drug
WordNet
- a drug used to treat or prevent convulsions (as in epilepsy) (同)anticonvulsant_drug, antiepileptic, antiepileptic_drug
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/18 14:08:23」(JST)
wiki en
Anticonvulsants (also commonly known as antiepileptic drugs or as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the rapid and excessive firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Some investigators have observed that anticonvulsants themselves may cause reduced IQ in children.[1] However these adverse effects must be balanced against the significant risk epileptic seizures pose to children and the distinct possibility of death and devastating neurological sequelae secondary to seizures. Anticonvulsants are more accurately called antiepileptic drugs (abbreviated "AEDs"), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.
Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action.[2] Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase.[3] Additional targets include voltage-gated calcium channels, SV2A, and α2δ.[4][5] By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatory glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA.[6] 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 proconvulsively.[6] Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.[7][8][9][10][11][12][13] The drug class was the 5th-best-selling in the US in 2007.[14]
Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy.[15] 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).[16]
Contents
- 1 Approval
- 2 Drugs
- 2.1 Aldehydes
- 2.2 Aromatic allylic alcohols
- 2.3 Barbiturates
- 2.4 Benzodiazepines
- 2.5 Bromides
- 2.6 Carbamates
- 2.7 Carboxamides
- 2.8 Fatty acids
- 2.9 Fructose derivatives
- 2.10 GABA analogs
- 2.11 Hydantoins
- 2.12 Oxazolidinediones
- 2.13 Propionates
- 2.14 Pyrimidinediones
- 2.15 Pyrrolidines
- 2.16 Succinimides
- 2.17 Sulfonamides
- 2.18 Triazines
- 2.19 Ureas
- 2.20 Valproylamides (amide derivatives of valproate)
- 2.21 Other
- 3 Non-medical anticonvulsants
- 4 Treatment guidelines
- 5 History
- 5.1 Marketing approval history
- 6 Use in pregnancy
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
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.[16] 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.[16]
Drugs
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In the following list, the dates in parentheses are the earliest approved use of the drug.
Aldehydes
Main article: Aldehyde
- Paraldehyde (1882). One of the earliest anticonvulsants. It is 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 Dravet syndrome.[17][18]
Barbiturates
Main article: Barbiturate
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 (1912). See also the related drug primidone.
- Methylphenobarbital (1935). Known as mephobarbital in the US. No longer marketed in the UK
- Barbexaclone (1982). Only available in some European countries.
Phenobarbital was the main anticonvulsant from 1912 until 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: Benzodiazepine
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.[19][20][21][22] 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: Bromide
- Potassium bromide (1857). The earliest effective treatment for epilepsy. There would not be a better drug until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.
Carbamates
Main article: Carbamate
- Felbamate (1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.[23][24][25]
Carboxamides
Carbamazepine
Main article: Carboxamide
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 and is also available generically.
- Eslicarbazepine acetate (2009)
Fatty acids
Main article: Fatty acid
The following are fatty-acids:
- The valproates — valproic acid, sodium valproate, and divalproex sodium (1967).
- Vigabatrin (1989).
- Progabide
- Tiagabine (1996).
Vigabatrin and progabide are also analogs of GABA.
Fructose derivatives
Main article: Fructose
- Topiramate (1995).
GABA analogs
- Gabapentin (1993).
- Pregabalin (2004).
Hydantoins
Main article: Hydantoin
The following are hydantoins:
- Ethotoin (1957).
- Phenytoin (1938).
- Mephenytoin
- Fosphenytoin (1996).
Oxazolidinediones
Main article: Oxazolidinedione
The following are oxazolidinediones:
- Paramethadione
- Trimethadione (1946).
- Ethadione
Propionates
Main article: Propionate
- Beclamide
Pyrimidinediones
Main article: Pyrimidinedione
- Primidone (1952).
Pyrrolidines
Main article: Pyrrolidine
- Brivaracetam
- Levetiracetam (1999).
- Seletracetam
Succinimides
Main article: Succinimide
The following are succinimides:
- Ethosuximide (1955).
- Phensuximide
- Mesuximide
Sulfonamides
Main article: Sulfonamide (medicine)
- Acetazolamide (1953).
- Sultiame
- Methazolamide
- Zonisamide (2000).
Triazines
Main article: Triazine
- Lamotrigine (1990).
Ureas
Main article: Urea
- Pheneturide
- Phenacemide
Valproylamides (amide derivatives of valproate)
Main article: Amide
- Valpromide
- Valnoctamide
Other
- Perampanel
Non-medical anticonvulsants
This article is about anticonvulsant drugs. For non-medical "anticonvulsants", see Epilepsy#Other treatment.
Sometimes, ketogenic diet or vagus nerve stimulation are described as "anticonvulsant" therapies as well.
Treatment guidelines
According to guidelines by the AAN and AES,[26] mainly based on a major article review in 2004,[27] patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such as carbamazepine, phenytoin, valproic acid/valproate semisodium, phenobarbital, or on the newer anticonvulsants gabapentin, lamotrigine, oxcarbazepine or topiramate. The choice of anticonvulsants depends on individual patient characteristics.[26] Both newer and older drugs are generally equally effective in new onset epilepsy.[26] The newer drugs tend to have fewer side effects.[26] For newly diagnosed partial or mixed seizures, there is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate as monotherapy.[26] Lamotrigine can be included in the options for children with newly diagnosed absence seizures.[26]
History
The first anticonvulsant was bromide, suggested in 1857 by Charles Locock who used it to treat women with "hysterical epilepsy" (probably catamenial epilepsy). Bromides are effective against epilepsy, and also cause impotence, which is not related to its anti-epileptic effects. Bromide also suffered from the way it affected behaviour, introducing the idea of the 'epileptic personality' which was actually a result of medication. Phenobarbital was first used in 1912 for both its sedative and antiepileptic properties. By the 1930s, the development of animal models in epilepsy research led to the development of phenytoin by Tracy Putnam and H. Houston Merritt, which had the distinct advantage of treating epileptic seizures with less sedation.[28] By the 1970s, a National Institutes of Health initiative, the Anticonvulsant Screening Program, headed by J. Kiffin Penry, served as a mechanism for drawing the interest and abilities of pharmaceutical companies in the development of new anticonvulsant medications.
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 | 1953-07-2727 July 1953[29] | 1988[30] | |
| carbamazepine | Tegretol | 1974-07-1515 July 1974[31][32] | 1965[30] | 1963[33] |
| clobazam | Frisium | 1979[30] | ||
| clonazepam | Klonopin/Rivotril | 1975-06-044 June 1975[34] | 1974[30] | |
| diazepam | Valium | 1963-11-1515 November 1963[35] | ||
| divalproex sodium | Depakote | 1983-03-1010 March 1983[36] | ||
| eslicarbazepine | Data needed | |||
| ethosuximide | Zarontin | 1960-11-022 November 1960[37] | 1955[30] | 1962[33] |
| ethotoin | Peganone | 1957-04-2222 April 1957[38] | ||
| felbamate | Felbatol | 1993-07-2929 July 1993[39] | ||
| fosphenytoin | Cerebyx | 1996-08-055 August 1996[40] | ||
| gabapentin | Neurontin | 1993-12-3030 December 1993[41] | 1993-05May 1993[30][33] | 1994-10October 1994[33] |
| lamotrigine | Lamictal | 1994-12-2727 December 1994[42] | 1991-10October 1991[30][33] | 1995-05May 1995[33] |
| lacosamide | Vimpat | 2008-10-2828 October 2008[43] | ||
| levetiracetam | Keppra | 1999-11-3030 November 1999[44] | 2000-09-2929 September 2000[30][45] | 2000-09-2929 September 2000[45] |
| mephenytoin | Mesantoin | 1946-10-2323 October 1946[46] | ||
| metharbital | Gemonil | 1952[47][48] | ||
| methsuximide | Celontin | 1957-02-088 February 1957[49] | ||
| methazolamide | Neptazane | 1959-01-2626 January 1959[50] | ||
| oxcarbazepine | Trileptal | 2000-01-1414 January 2000[51] | 2000[30] | |
| phenobarbital | 1912[30] | 1920[33] | ||
| phenytoin | Dilantin/Epanutin | 1938[33][52] | 1938[30] | 1941[33] |
| phensuximide | Milontin | 1953[53][54] | ||
| pregabalin | Lyrica | 2004-12-3030 December 2004[55] | 2004-07-066 July 2004[30][56] | 2004-07-066 July 2004[56] |
| primidone | Mysoline | 1954-03-088 March 1954[57] | 1952[30] | 1953[33] |
| sodium valproate | Epilim | 1977-12December 1977[33] | 1967-06June 1967[33] | |
| stiripentol | Diacomit | 2001-12-055 December 2001[58] | 2001-12-055 December 2001[58] | |
| tiagabine | Gabitril | 1997-09-3030 September 1997[59][60] | 1998[30] | 1997-11November 1997[33] |
| topiramate | Topamax | 1996-12-2424 December 1996[61] | 1995[30] | |
| trimethadione | Tridione | 1946-01-2525 January 1946[62] | ||
| valproic acid | Depakene/Convulex | 1978-02-2828 February 1978[63] | 1993[30] | |
| vigabatrin | Sabril | 2009-08-2121 August 2009[64] | 1989[30] | |
| zonisamide | Zonegran | 2000-03-2727 March 2000[65] | 2005-03-1010 March 2005[30][66] | 2005-03-1010 March 2005[66] |
Use in pregnancy
During pregnancy, the metabolism of several 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.[67] Therefore, these drugs should be monitored during use in pregnancy.[67]
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.[68] On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure.[68] 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.[68]
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.[67]
Regarding breastfeeding, some anticonvulsants probably pass into breast milk in clinically significant amounts, including primidone and levetiracetam.[67] On the other hand, valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts.[67]
In animal models, several anticonvulsant drugs have been demonstrated to induce neuronal apoptosis in the developing brain.[69][70][71][72][73]
See also
- ATC code N03
References
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- ^ https://www.neurology.wisc.edu/publications/2010%20pubs/stafstrom-4.pdf
- ^ Rogawski MA, Löscher W; Löscher (July 2004). "The neurobiology of antiepileptic drugs". Nature Reviews Neuroscience 5 (7): 553–64. doi:10.1038/nrn1430. PMID 15208697.
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Doc.Ref.: EMEA/COMP/269/04
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- ^ 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.
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- ^ NDA 008943
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- ^ NDA 016608 (Initial approval on 11 March 1968 was for trigeminal neuralgia.)
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- ^ NDA 017533
- ^ NDA 013263
- ^ NDA 018723
- ^ NDA 012380
- ^ NDA 010841
- ^ NDA 020189
- ^ NDA 020450
- ^ NDA 020235
- ^ NDA 020241
- ^ NDA 022253
- ^ NDA 021035
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- ^ NDA 006008
- ^ NDA 008322
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- ^ NDA 010596
- ^ NDA 011721
- ^ NDA 021014
- ^ NDA 008762 (Marketed in 1938, approved 1953)
- ^ NDA 008855
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- ^ NDA 021446
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- ^ NDA 009170
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- ^ NDA 020646
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- ^ NDA 020505
- ^ NDA 005856
- ^ NDA 018081
- ^ Lundbeck Press Release
- ^ NDA 020789
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- ^ Katz I, Kim J et al. (Aug 2007). "Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain". J Pharmacol Exp Ther 322 (2): 494–500. doi:10.1124/jpet.107.123133. PMID 17483293.
- ^ Kim J, Kondratyev A, and Gale K (Oct 2007). "Antiepileptic drug-induced neuronal cell death in the immature brain: effects of carbamazepine, topiramate, and levetiracetam as monotherapy versus polytherapy". J Pharmacol Exp Ther 323 (1): 165–73. doi:10.1124/jpet.107.126250. PMC 2789311. PMID 17636003.
- ^ Forcelli PA, Kim J et al. (Dec 2011). "Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain". Epilepsia 52 (12): e207–11. doi:10.1111/j.1528-1167.2011.03297.x. PMC 3230752. PMID 22050285.
Further reading
- Anti epileptic activity of novel substituted fluorothiazole derivatives by Devid Chutia, RGUHS
External links
- eMedicine: Antiepileptic Drugs: an overview
- NINDS: Anticonvulsant Screening Program
- Use of Anticonvulsants in Pharmacotherapy of Bronchial Asthma
- MDNG: Anticonvulsants and Bone Health
- Miami Children's Brain Institute - Anticonvulsants
- Drug Reference for FDA Approved Epilepsy Drugs
- Epilepsy Action: UK Anti-Epileptic Drugs List
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UpToDate Contents
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- 1. 抗てんかん剤：作用機序、薬理学、および有害事象 antiepileptic drugs mechanism of action pharmacology and adverse effects
- 2. 成人におけるてんかんのマネージメントの概要 overview of the management of epilepsy in adults
- 3. Seizures and epilepsy in children: Initial treatment and monitoring
- 4. 成人におけるてんかんの外科的治療 surgical treatment of epilepsy in adults
- 5. 抗てんかん剤と骨疾患 antiepileptic drugs and bone disease
English Journal
- Anticonvulsant Activity of Extracts of Plectranthus barbatus Leaves in Mice.
- Borges Fernandes LC, Campos Camara C, Soto-Blanco B.SourceDepartamento de Ciencias Animais, Universidade Federal Rural do Semi-Arido (UFERSA), BR 110 Km 47, 59625-900 Mossoro, RN, Brazil.
- Evidence-based complementary and alternative medicine : eCAM.Evid Based Complement Alternat Med.2012;2012:860153. Epub 2011 Jun 9.
- Plectranthus barbatus is a medicinal plant used to treat a wide range of disorders including seizure. However, the anticonvulsant activity of this plant has not been studied in depth. We therefore sought to evaluate the anticonvulsant activity of a hydroalcoholic extract of P. barbatus leaves on sei
- PMID 21716675
- Study on the absolute configuration of levetiracetam via density functional theory calculations of electronic circular dichroism and optical rotatory dispersion.
- Li L, Si YK.SourceInstitute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union of Medical College, 1 Xian Nong Tan Street, Beijing 100050, PR China.
- Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2011 Nov 1;56(3):465-70. Epub 2011 Jul 7.
- Theoretical calculation of chiroptical properties has been a powerful tool for the absolute configuration assignment of chiral compounds including synthetic drugs and natural products. In the present work, time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism
- PMID 21794998
- Endocannabinoid system dysfunction in mood and related disorders.
- Ashton CH, Moore PB.SourceDepartment of Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
- Acta psychiatrica Scandinavica.Acta Psychiatr Scand.2011 Oct;124(4):250-61. doi: 10.1111/j.1600-0447.2011.01687.x. Epub 2011 Mar 9.
- Ashton CH, Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Objective:? The endocannabinoid (EC) system is widely distributed throughout the brain and modulates many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous ca
- PMID 21916860
Japanese Journal
- セミナー/カンファレンスシリーズ(第21回)Drug Induced Hypersensitivity Syndrome(DIHS)を呈した統合失調症の一例--国立国際医療研究センター国府台病院 精神科カンファレンスから
- 草西 俊,伊藤 寿彦
- 医療 65(4), 221-226, 2011-04
- NAID 40018869637
- フェニトインの長期内服が筋弛緩薬に対する抵抗性の一因として疑われた精神発達遅滞の1症例
- 吉良 慎一郎
- 麻酔 60(1), 80-83, 2011-01
- NAID 40017424757
- Nonconvulsive Status Epilepticus During Perioperative Period of Cerebrovascular Surgery
- MORIOKA Takato,SAYAMA Tetsuro,MUKAE Nobutaka,HAMAMURA Takeshi,YAMAMOTO Kuniko,KIDO Tomomi,SAKATA Ayumi,SASAKI Tomio
- Neurologia medico-chirurgica 51(3), 171-179, 2011
- … Improved mental status and consciousness level, together with disappearance of EEG abnormalities, after appropriate anticonvulsant treatment supported the diagnosis of NCSE. …
- NAID 130000677024
Related Links
- 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, and in ...
- 無料日本語辞書で'anticonvulsant'を翻訳してから、他の日本語翻訳をチェック。
Related Pictures
★リンクテーブル★
| リンク元 | 「antiseizure drug」「抗痙攣」「抗けいれん」「antiseizure」「anticonvulsive」 |
| 拡張検索 | 「anticonvulsant agent」 |
| 関連記事 | 「anticonvulsants」 |
「antiseizure drug」
- 関
- specific agents
「抗痙攣」
「抗けいれん」
「antiseizure」
- adj.
- 抗痙攣の、抗けいれんの、抗てんかん性の
「anticonvulsive」
- 抗痙攣の、抗けいれんの
「anticonvulsant agent」
「anticonvulsants」
- 関
- anticonvulsant、anticonvulsant agent、anticonvulsant drug、antiepileptic agent、antiepileptic drug、antiepileptics、antiseizure drug
- 関
- Antiseizure drug(s)