مضادات التشنج

(تم التحويل من مضادات الصرع)
مضادات التشنج
صف عقاقير
مميزات الصف
المرادفاتAntiepileptic drugs, antiseizure drugs
الاستخدامEpilepsy
كود ATCN03
الهدف الحيويBrain
[[d:خطأ لوا في وحدة:Wikidata على السطر 866: attempt to index field 'wikibase' (a nil value). |In Wikidata]]

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.[1] Anticonvulsants are also increasingly being used in the treatment of bipolar disorder[2][3] and borderline personality disorder,[4] since many seem to act as mood stabilizers, and for the treatment of neuropathic pain.[5] Anticonvulsants suppress the excessive rapid firing of neurons during seizures.[6] Anticonvulsants also prevent the spread of the seizure within the brain.[7]

Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action.[8] 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.[9] Additional targets include voltage-gated calcium channels, SV2A, and α2δ.[10][11] 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.[12] 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.[12] Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.[13][14][15][16][17][18][19] The drug class was the fifth-best-selling in the United States in 2007.[20]

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy.[21] 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).[22]

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المصطلحات

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.


الأدوية المضادة للصرع

ومضادات الصرع هي مجموعة متنوعة من الأدوية المستخدمة في علاج نوبات الصرع. ومضادات الصرع أيضا أصبحت تستخدم بشكل متزايد في علاج الإضطراب ثنائي القطب و بينما يبدو أن الكثير من تلك العقاقير تعد بمثابة مثبتات للمزاج.فإن الهدف من مضادات الصرع هو منع الإشتعال السريع والمفرط لتيارات الخلايا العصبية التي تبدأ النوبة. وبسبب هذا ، فإن مضادات أثبتت فعاليتها في علاج أنواع كثيرة من القلق ذى الخلل الوظيفى. وإذا تعذر ذلك ، فإن وجود مضاد فعال في منع انتشار الاستيلاء داخل الدماغ ، وتوفر حماية ضد آثار excitotoxic الممكنة التي قد تؤدي إلى تلف في المخ. ومع ذلك ، مضادات أنفسهم وقد تم ربط خفض معدل الذكاء لدى الأطفال [1]. مضادات الاختلاج غالبا ما تسمى أدوية الصرع (مختصر "AEDs") ، على الرغم من إسم عقاقير antiseizure قد يكون من الأنسب نظرا لأن "AEDs" يمكن أن تحدث تغيرا في الحالة المرضية.

الأهداف الرئيسية الجزيئية من عقاقير مضادات الصرع التى يتم تسويقها هى عقاقير تستهدف فرق الجهد لبوابات قنوات الصوديوم ومكونات نظام غابا ، بما في ذلك مستقبلات GABAA ، والجات - 1 وناقلات غابا ، وغابا transaminase. 2] المزيد من الأهداف تشمل البوابات المستهدفة لفرق الجهد لقنوات الكالسيوم SV2A, and α2δ. [3][4].

بعض مضادات أظهرت آثارا antiepileptogenic في نماذج حيوانية لعلاج الصرع. وهذا هو ، لأنها إما أنها تمنع التطور المتوقع من الصرع أو يمكن أن توقف أو تعكس تطور الصرع. ومع ذلك ، لا يوجد أي دواء لمنع epileptogenesis (تنمية الصرع بعد إصابة مثل إصابة في الرأس) في التجارب على البشر [5].


ينتج الصرع Epilepsy عن اضطرابات فجائية ذات إفراغ شاذ وزائد في العصبونات الدماغية.حيث تبدأ النوبة بإفراغ شحنة شاذة محلية، ثم تنتشر في المناطق الأخرى من الدماغ، فإذا انتشرت على نصف كرة مخية واحدة يسمى بالصرع البؤري ، أما إذا انتشرت على الدماغ بأكمله فإنه يسمى بالصرع المعمم.


العقاقير المضادة للصرع

فى القائمة التالية, التواريخ بين الأقواس هى الأقدم من حيث الموافقات على إقرار الدواء .

الألديهات

المقالة الرئيسية: الألديهات

  • بارالديهايد (1882). و يعد واحدا من أقدم مضادات الصرع . و مايزال قيد الإستخدام في حالات status epilepticus , وخاصة حيث لا توجد مرافق إنعاش.

الكحول الأليلى العطرى

  • Stiripentol (2001 - توافر محدود). يوصف لعلاج آثار شديدة myoclonic الصرع لدى الأطفال (SMEI).

الباربيتيورات

''المقالة الرئيسية: الباربيتيورات

الباربيتيورات هى عقاقير والتي تكون بمثابة مثبطات الجهاز العصبي المركزي(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.


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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.[23][24][25][26] Of the many drugs in this class, only a few are used to treat epilepsy:

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 and is also available generically.
  • Eslicarbazepine acetate (2009)


أسباب الصرع

لم يتحدد سبب واضح له حتى الآن، لكن يعتقد بأن الصرع قد يحدث للأسباب التالية:

1. أي أذية دماغية يمكن أن تعبر كعامل مؤهب لحدوث الصرع، مثل: الرضوض – النزف - الأورام الدماغية – الانتانات السحائية.

2. متلازمات عصبية.

3. تغير العوامل المحيطية (انخفاض السكر، تناذر السحب السريع للكحول، تغير PH الدم أو الغازات أو الشوارد).


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أنواع الصرع

A. الجزئي أو البؤري Partial Epilepsy :

ينجم عن زيادة الفعالية الكهربائية في نصف الكرة المخية الواحدة. ويصنف إلى :

أولاً : الصرع الجزئي البسيط Simple Partial Epilepsy:

حيث تقتصر الفعالية الكهربائية على بؤرة واحدة صغيرة في المنطقة القشرية الحركية، ويبدي المريض غالباً فعالية شاذة في طرف أو عضلة منفردة، و لا يترافق بفقدان الوعي.

ثانياً : الصرع الجزئي المعقد Complex Partial Epilepsy:

و هنا تشمل النوبة هزة عنيفة متكررة لمجموعة عضلية معنية تبدأ من جهة واحدة من الجسم ، غالباً ما تكون الإبهام أو زاوية الفم، ثم تنتشر ويمكن أن تشمل معظم الجسم خلال دقيقتين.و يتميز هذا النوع من الصرع بفقدان وعي المريض و باضطرابات حركية تشمل :البلع – الإسهال – التبول.تكون النوبة في البداية موضعية، لكنها لا تلبث أن تنتشر مسببة تفريغاً كهربائياً شاذاً يشمل كامل نصفي الكرتين المخيتين.

B.الصرع المعمم Generalized Epilepsy:

يتميز هذا الصرع بفقدان المريض للوعي فجأة وبشكل فوري، حيث تكون النوبة في البداية موضعية، لكنها تصبح منتشرة مسببة تفريغ كهربائي شاذ يشمل كامل نصفي الكرتين المخيتين.

و يقسم الصرع المعمم إلى :

ا- الصرع المقوي الخلجاني (الصرع الكبير) (Tonic-Clonic (Grand mal: تبدأ النوبة بفقدان الوعي، ثم يتبعها الطور المقوي- وهو تقلص مستمر،يصبح الوجه أزرق ومنتفخ فيها خلال دقيقة.

ثم الطور الخلجاني: وهو تقلص سريع + ارتخاء سريع، ثم تخليط ذهني وإنهاك.

2- نوبات الغيبوبة (الصرع الصغير) (Absence-Seizures (Petit mal :

يبدأ من عمر 3 – 5 سنوات، ويستمر حتى البلوغ، و يتميز بفقدان وعي مفاجئ وقصير الأمد.

3- الحالة الصرعية Status Epileptics:

حيث تكون النوبات معاودة بسرعة دون أن يرجع المريض إلى وعيه.

4- الصرع العضلي الخلجاني Myo-Clonic:

يحدث هذا الصرع في جميع الأعمار ، و هو عبارة عن سلسلة من التقلصات العضلية القصيرة تشمل: الوجه – الجذع – الأطراف. تنتج غالباً عن أذية عصبية دائمة مكتسبة تالية لنقص الأكسجة، أو التهاب الدماغ، أو الانسمام الدوائي.

5- النوبات الحرورية Febrile Seizure:

تحدث عند الأطفال بعمر 3 أشهر إلى 5 سنوات، نتيجة ارتفاع الحرارة.و تتميز بنوب مقوية خلجانية معممة قصيرة الأمد،و نادراً ما تتطلب المعالجة الدوائية، إذ أنها لا تسبب الموت أو أية أذية عصبية.

6- متلازمة Lennox-Gastaut:

و هو نوع حاد جداً من الصرع. يحدث عند الأطفال، ويرتبط بالتأخر العقلي المتطور.

تاريخ الموافقة على التسويق

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.

العقار الاسم التجاري US UK فرنسا
acetazolamide Diamox 1953-07-2727 July 1953[27] 1988[28]
brivaracetam Briviact 2016-02-1818 February 2016[29][30]
carbamazepine Tegretol 1974-07-1515 July 1974[31][32] 1965[28] 1963[33]
cenobamate Xcopri 2019-11-2121 November 2019
clobazam Onfi/Frisium 2011-10-2121 October 2011[34][35] 1979[28]
clonazepam Klonopin/Rivotril 1975-06-044 June 1975[36] 1974[28]
diazepam Valium 1963-11-1515 November 1963[37]
divalproex sodium Depakote 1983-03-1010 March 1983[38]
eslicarbazepine Aptiom 2013-08-1111 August 2013[39][40]
ethosuximide Zarontin 1960-11-022 November 1960[41] 1955[28] 1962[33]
ethotoin Peganone 1957-04-2222 April 1957[42]
everolimus Afinitor/Votubia 2009-03-3030 January 2009[43]
felbamate Felbatol 1993-07-2929 July 1993[44]
fosphenytoin Cerebyx 1996-08-055 August 1996[45]
gabapentin Neurontin 1993-12-3030 December 1993[46] 1993-05May 1993[28][33] 1994-10October 1994[33]
lacosamide Vimpat 2008-10-2828 October 2008[47]
lamotrigine Lamictal 1994-12-2727 December 1994[48] 1991-10October 1991[28][33] 1995-05May 1995[33]
levetiracetam Keppra 1999-11-3030 November 1999[49] 2000-09-2929 September 2000[28][50] 2000-09-2929 September 2000[50]
mephenytoin Mesantoin 1946-10-2323 October 1946[51]
metharbital Gemonil 1952[52][53]
methsuximide Celontin 1957-02-088 February 1957[54]
methazolamide Neptazane 1959-01-2626 January 1959[55]
oxcarbazepine Trileptal 2000-01-1414 January 2000[56] 2000[28]
phenobarbital 1912[28] 1920[33]
phenytoin Dilantin/Epanutin 1938[33][57] 1938[28] 1941[33]
piracetam Nootropil Data needed
phensuximide Milontin 1953[58][59]
pregabalin Lyrica 2004-12-3030 December 2004[60] 2004-07-066 July 2004[28][61] 2004-07-066 July 2004[61]
primidone Mysoline 1954-03-088 March 1954[62] 1952[28] 1953[33]
rufinamide Banzel/Inovelon 2008-11-1414 November 2008[63][64]
sodium valproate Epilim 1977-12December 1977[33] 1967-06June 1967[33]
stiripentol Diacomit 2018-08-2020 August 2018[65][66] 2001-12-055 December 2001[67] 2001-12-055 December 2001[67]
tiagabine Gabitril 1997-09-3030 September 1997[68][69] 1998[28] 1997-11November 1997[33]
topiramate Topamax 1996-12-2424 December 1996[70] 1995[28]
trimethadione Tridione 1946-01-2525 January 1946[71]
valproic acid Depakene/Convulex 1978-02-2828 February 1978[72] 1993[28]
vigabatrin Sabril 2009-08-2121 August 2009[73] 1989[28]
zonisamide Zonegran 2000-03-2727 March 2000[74] 2005-03-1010 March 2005[28][75] 2005-03-1010 March 2005[75]


الحمل

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.[76] Therefore, these drugs should be monitored during use in pregnancy.[76]

Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbitol, gabapentin have been reported to cause increased risk of birth defects.[77] Among anticonvulsants, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects. The risk of untreated epilepsy is believed to be greater than the risk of adverse effects caused by these medications, necessitating continuation of antiepileptic treatment.

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.[78] On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure.[78] 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.[78]

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.[76]

Regarding breastfeeding, some anticonvulsants probably pass into breast milk in clinically significant amounts, including primidone and levetiracetam.[76] On the other hand, valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts.[76]

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.[79]

Pregnancy planning is being explored as a method that could decrease the risk of possible birth defects. Since the first trimester is the most susceptible period for fetal development, planning a routine antiepileptic drug dose that is safer for the first trimester could be beneficial to prevent pregnancy complications.[80]

In animal models, several anticonvulsant drugs have been demonstrated to induce neuronal apoptosis in the developing brain.[81][82][83][84][85]

المراجع

  1. ^ Al-Otaibi, Faisal (2019-09-01). "An overview of structurally diversified anticonvulsant agents". Acta pharmaceutica (Zagreb, Croatia). Walter de Gruyter GmbH. 69 (3): 321–344. doi:10.2478/acph-2019-0023. ISSN 1846-9558. PMID 31259739.
  2. ^ Joshi, A; Bow, A; Agius, M (2019). "Pharmacological Therapies in Bipolar Disorder: a Review of Current Treatment Options". Psychiatria Danubina. 31 (Suppl 3): 595–603. ISSN 0353-5053. PMID 31488797.
  3. ^ Keck, Jr., Paul E.; McElroy, Susan L.; Strakowski, Stephen M. (1998). "Anticonvulsants and antipsychotics in the treatment of bipolar disorder". The Journal of Clinical Psychiatry. 59 (Suppl 6): 74–82. PMID 9674940.
  4. ^ 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.
  5. ^ Rogawski, Michael A.; Löscher, Wolfgang (2004). "The neurobiology of antiepileptic drugs". Nature Reviews Neuroscience. 5 (7): 553–564. doi:10.1038/nrn1430. PMID 15208697.
  6. ^ McLean, M J; Macdonald, R L (June 1986). "Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture". Journal of Pharmacology and Experimental Therapeutics. 237 (3): 1001–1011.
  7. ^ Harden, C. L. (1 May 1994). "New antiepileptic drugs". Neurology. 44 (5): 787–95. doi:10.1212/WNL.44.5.787. PMID 8190276.
  8. ^ "Archived copy" (PDF). Archived from the original (PDF) on 3 November 2013. Retrieved 2013-01-28.CS1 maint: archived copy as title (link)
  9. ^ Rogawski MA, Löscher W (July 2004). "The neurobiology of antiepileptic drugs". Nature Reviews Neuroscience. 5 (7): 553–64. doi:10.1038/nrn1430. PMID 15208697.
  10. ^ Rogawski MA, Bazil CW (July 2008). "New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels". Curr Neurol Neurosci Rep. 8 (4): 345–52. doi:10.1007/s11910-008-0053-7. PMC 2587091. PMID 18590620.
  11. ^ Meldrum BS, Rogawski MA (January 2007). "Molecular targets for antiepileptic drug development". Neurotherapeutics. 4 (1): 18–61. doi:10.1016/j.nurt.2006.11.010. PMC 1852436. PMID 17199015.
  12. ^ أ ب Kammerer, M.; Rassner, M. P.; Freiman, T. M.; Feuerstein, T. J. (2 May 2011). "Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes". Naunyn-Schmiedeberg's Archives of Pharmacology. 384 (1): 47–57. doi:10.1007/s00210-011-0636-8. PMID 21533993.
  13. ^ Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, et al. (2013). Charpier S (ed.). "PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings". PLoS ONE. 8 (5): e64541. doi:10.1371/journal.pone.0064541. PMC 3664607. PMID 23724059.
  14. ^ Citraro R, et al. (2013). "Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy". Neuropharmacology. 69: 115–26. doi:10.1016/j.neuropharm.2012.11.017. PMID 23206503.
  15. ^ Porta, N.; Vallée, L.; Lecointe, C.; Bouchaert, E.; Staels, B.; Bordet, R.; Auvin, S. (2009). "Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, exerts anticonvulsive properties". Epilepsia. 50 (4): 943–8. doi:10.1111/j.1528-1167.2008.01901.x. PMID 19054409.
  16. ^ Lampen A, Carlberg C, Nau H (2001). "Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives". Eur J Pharmacol. 431 (1): 25–33. doi:10.1016/S0014-2999(01)01423-6. PMID 11716839.
  17. ^ Maguire JH, Murthy AR, Hall IH (1985). "Hypolipidemic activity of antiepileptic 5-phenylhydantoins in mice". Eur J Pharmacol. 117 (1): 135–8. doi:10.1016/0014-2999(85)90483-2. PMID 4085542.
  18. ^ Hall IH, Patrick MA, Maguire JH (1990). "Hypolipidemic activity in rodents of phenobarbital and related derivatives". Arch Pharm (Weinheim). 323 (9): 579–86. doi:10.1002/ardp.19903230905. PMID 2288480.
  19. ^ Frigerio F, Chaffard G, Berwaer M, Maechler P (2006). "The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the fatty acid oleate". Biochem Pharmacol. 72 (8): 965–73. doi:10.1016/j.bcp.2006.07.013. PMID 16934763.
  20. ^ http://www.joacp.org/index.php?option=com_content&view=article&id=188&catid=1[dead link] "According to the Washington Post who quoted research from IMS Health, AEDs were the fifth best selling class of drugs in the United States in 2007, with sales topping 10 billion dollars. "
  21. ^ Kaminski, R. M.; Rogawski, M. A.; Klitgaard, H (2014). "The potential of antiseizure drugs and agents that act on novel molecular targets as antiepileptogenic treatments". Neurotherapeutics. 11 (2): 385–400. doi:10.1007/s13311-014-0266-1. PMC 3996125. PMID 24671870.
  22. ^ Abou-Khalil BW (2007). "Comparative Monotherapy Trials and the Clinical Treatment of Epilepsy". Epilepsy Currents. 7 (5): 127–9. doi:10.1111/j.1535-7511.2007.00198.x. PMC 2043140. PMID 17998971.
  23. ^ Browne TR (1976). "Clonazepam. A review of a new anticonvulsant drug". Arch Neurol. 33 (5): 326–32. PMID 817697. Unknown parameter |month= ignored (help)
  24. ^ Isojärvi, JI (1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability". J Intellect Disabil Res. 42 (1): 80–92. PMID 10030438. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  25. ^ Tomson T (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. Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  26. ^ Djurić, M (2001). "[West syndrome--new therapeutic approach]". Srp Arh Celok Lek. 129 (1): 72–7. PMID 15637997. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  27. ^ "New Drug Application (NDA) 008943". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  28. ^ أ ب ت ث ج ح خ د ذ ر ز س ش ص ض ط ظ ع Epilepsy Action: Druglist. Retrieved on 1 November 2007.
  29. ^ "New Drug Application (NDA) 205836". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  30. ^ "Drug Approval Package: Briviact (brivaracetam)". U.S. Food and Drug Administration (FDA). March 30, 2016. Archived from the original on 22 November 2019. Retrieved 21 November 2019.
  31. ^ "New Drug Application (NDA) 016608". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019. (Initial approval on 11 March 1968 was for trigeminal neuralgia.)
  32. ^ Schain, Richard J. (1 March 1978). "Pediatrics—Epitomes of Progress: Carbamazepine (Tegretol) in the Treatment of Epilepsy". Western Journal of Medicine. 128 (3): 231–232. PMC 1238063. PMID 18748164.
  33. ^ أ ب ت ث ج ح خ د ذ ر ز س ش Loiseau, Pierre Jean-Marie (June 1999). "Clinical Experience with New Antiepileptic Drugs: Antiepileptic Drugs in Europe". Epilepsia. 40 (Suppl 6): S3–8. doi:10.1111/j.1528-1157.1999.tb00925.x. PMID 10530675.
  34. ^ "New Drug Application (NDA) 202067". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  35. ^ "Drug Approval Package: Onfi NDA #202067". U.S. Food and Drug Administration (FDA). August 20, 2013. Archived from the original on 22 November 2019. Retrieved 21 November 2019.
  36. ^ "New Drug Application (NDA) 017533". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  37. ^ "New Drug Application (NDA) 013263". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  38. ^ "New Drug Application (NDA) 018723". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  39. ^ "New Drug Application (NDA) 022416". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  40. ^ "Drug Approval Package: Brand Name (Generic Name) NDA #". =U.S. Food and Drug Administration (FDA). December 20, 2013. Archived from the original on 22 November 2019. Retrieved 21 November 2019.
  41. ^ "New Drug Application (NDA) 012380". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  42. ^ "New Drug Application (NDA) 010841". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  43. ^ "New Drug Application (NDA) 022334". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  44. ^ "New Drug Application (NDA) 020189". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  45. ^ "New Drug Application (NDA) 020450". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  46. ^ "New Drug Application (NDA) 020235". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  47. ^ "New Drug Application (NDA) 022253". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  48. ^ "New Drug Application (NDA) 020241". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  49. ^ "New Drug Application (NDA) 021035". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  50. ^ أ ب EPAR: Keppra. Archived 19 June 2009 at the Wayback Machine. Retrieved on 1 November 2007.
  51. ^ "New Drug Application (NDA) 006008". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  52. ^ "New Drug Application (NDA) 008322". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  53. ^ Dodson, W. Edwin; Giuliano Avanzini; Shorvon, Simon D.; Fish, David R.; Emilio Perucca (2004). The treatment of epilepsy. Oxford: Blackwell Science. xxviii. ISBN 978-0-632-06046-7.
  54. ^ "New Drug Application (NDA) 010596". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  55. ^ "New Drug Application (NDA) 011721". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  56. ^ "New Drug Application (NDA) 021014". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  57. ^ "New Drug Application (NDA) 008762". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019. (Marketed in 1938, approved 1953)
  58. ^ "New Drug Application (NDA) 008855". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  59. ^ Kutt, Henn; Resor, Stanley R. (1992). The Medical treatment of epilepsy. New York: Dekker. p. 385. ISBN 978-0-8247-8549-9. (first usage)
  60. ^ "New Drug Application (NDA) 021446". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  61. ^ أ ب EPAR: Lyrica Archived 21 June 2009 at the Wayback Machine. Retrieved on 1 November 2007.
  62. ^ "New Drug Application (NDA) 009170". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  63. ^ "New Drug Application (NDA) 021911". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  64. ^ "Drug Approval Package: Banzel (Rufinamide) NDA #021911". U.S. Food and Drug Administration (FDA). May 30, 2012. Archived from the original on 22 November 2019. Retrieved 21 November 2019.
  65. ^ "New Drug Application (NDA) 206709". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  66. ^ "Drug Approval Package: Diacomit (stiripentol)". U.S. Food and Drug Administration (FDA). September 7, 2018. Archived from the original on 22 November 2019. Retrieved 21 November 2019.
  67. ^ أ ب EPAR: Diacomit. Archived 26 December 2009 at the Wayback Machine. Orphan designation: 5 December 2001, full authorisation: 4 January 2007 Retrieved on 1 November 2007.
  68. ^ "New Drug Application (NDA) 020646". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  69. ^ "NDA: 020646". DrugPatentWatch. Retrieved 19 May 2013.
  70. ^ "New Drug Application (NDA) 020505". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  71. ^ "New Drug Application (NDA) 005856". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  72. ^ "New Drug Application (NDA) 018081". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  73. ^ "New Drug Application (NDA) 020427". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  74. ^ "New Drug Application (NDA) 020789". Drugs@FDA. U.S. Food and Drug Administration (FDA). Retrieved 21 November 2019.
  75. ^ أ ب EPAR: Zonegran. Archived 13 July 2009 at the Wayback Machine. Retrieved on 1 November 2007
  76. ^ أ ب ت ث ج Harden CL, Pennell PB, Koppel BS, et al. (May 2009). "Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society". Epilepsia. 50 (5): 1247–55. doi:10.1111/j.1528-1167.2009.02130.x. PMID 19507305.
  77. ^ Weston, Jennifer; Bromley, Rebecca; Jackson, Cerian F.; Adab, Naghme; Clayton-Smith, Jill; Greenhalgh, Janette; Hounsome, Juliet; McKay, Andrew J.; Tudur Smith, Catrin (2016-11-07). "Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child". The Cochrane Database of Systematic Reviews. 11: CD010224. doi:10.1002/14651858.CD010224.pub2. ISSN 1469-493X. PMC 6465055. PMID 27819746.
  78. ^ أ ب ت Bromley, Rebecca; Weston, Jennifer; Adab, Naghme; Greenhalgh, Janette; Sanniti, Anna; McKay, Andrew J; Tudur Smith, Catrin; Marson, Anthony G (2014). "Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child". Reviews (10): CD010236. doi:10.1002/14651858.CD010236.pub2. PMID 25354543.
  79. ^ Jazayeri, Dana; Graham, Janet; Hitchcock, Alison; O'Brien, Terence J.; Vajda, Frank J.E. (2018). "Outcomes of pregnancies in women taking antiepileptic drugs for non-epilepsy indications". Seizure. 56: 111–114. doi:10.1016/j.seizure.2018.02.009. ISSN 1059-1311. PMID 29471258.
  80. ^ George, Ilena C. (2017). "Practice Current: How do you treat epilepsy in pregnancy?". Neurology: Clinical Practice. 7 (4): 363–371. doi:10.1212/cpj.0000000000000387. ISSN 2163-0402. PMC 5648199. PMID 29185530.
  81. ^ Bittigau P, Sifringer M, Genz K, et al. (May 2002). "Antiepileptic drugs and apoptotic neurodegenereation in the developing brain". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 15089–94. doi:10.1073/pnas.222550499. PMC 137548. PMID 12417760.
  82. ^ Manthey D, Asimiadou S, et al. (Jun 2005). "Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain". Exp Neurol. 193 (2): 497–503. doi:10.1016/j.expneurol.2005.01.006. PMID 15869952.
  83. ^ 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.
  84. ^ Kim J, Kondratyev A, 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.
  85. ^ 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.

للاستزادة

  • Anti epileptic activity of novel substituted fluorothiazole derivatives by Devid Chutia, RGUHS

وصلات خارجية