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мен кэдеге жаратылуын, Т1ндерд1 ;амтамасыз етшуш жа;сартады. MMSE шкаласы бойынша зерттегенде нау;астардын, жагдайы емнен кей1н жа;сарганы бай^алган. Цорытынды:
Актовегиннщ ;олдануы тшмдшпн зерттеу нэтижес1, когнитивт1 функциялардын, жэне перефериялы; жуйкенщ жа;сарганын керсетт1. Осыган суйене, ;ант диабет1нен болган неврологиялы; ас;ынуларды емдеуге Актовегинд1 усынуга болады.
ЭДЕБИЕТТЕР Т1З1М1
1 Строков И.А., Альбекова Ж.С. Нервно- мышечные болезни. - 2003. - №1. - 25 с.
2 Строков И.А., Захаров В.В., Строков К.И. Неврология, нейропсихиатрия, психосоматика. - 2012. - № 1 - С. 64-74.
3 Бурчинский, С.Г. Современные подходы к нейропротекции // Новости медицины и фармации. - 2004. - С.10-11.
4 Ефимов А.С. Диабетические ангиопатии.- М.: 2000. - №3 - С. 54-58.
5 Салтыков Б.Б., Пауков В.С. Диабетические микроангиопатии.- М.: 2002. - С.47-50.
Б.Р. НУРМУХАМБЕТОВА, С.Б ЕСЕНТАЕВА, Б.К. ДЕМЕСИНОВА
Казахский Национальный медицинский университет имени С.Д. Асфендиярова
ЛЕЧЕНИЕ КОГНИТИВНЫХ РАССТРОЙСТВ У БОЛЬНЫХ С ДИАБЕТИЧЕСКОЙ ЭНЦЕФАЛОПАТИЕЙ
Резюме: Результаты исследования эффективности применение препарата Актовегина показали улучшение как когнитивных функций, так и состояния периферических нервов, что позволяет рекомендовать Актовегин для лечения неврологических осложнений СД.
Ключевые слова: диабетическая энцефалопатия, шкала MMSE, когнитивные нарушения .
B.R. NURMUKHAMBETOVA, S.B. ESENTAYEVA, B.K. DEMESINOVA
Asfendiyarov Kazakh National Medical University
TREATMENT OF COGNITIVE IMPAIRMENT IN PATIENTS WITH DIABETIC ENCEPHALOPATHY
Resume: The results of research of efficiency of intravenous introduction of Actovegin showed an improvement on a background treatment of both cognitive functions and state of peripheral nerves, that allows to recommend Actovegina for treatment of neurological complications of diabetes mellitusae. Keywords: diebitic encelophaty, MMSE scale, cognitive dysfunctions.
EPILEPSY AND PREGNANCY: AN ANALYSIS OF THE EFFECTIVENESS OF ANTI-EPILEPTIC DRUGS AND TERATOGENICITY
T.T. KISPAYEVA, A. S. NURAKHMETOVA
Karaganda State Medical University
УДК 616.853.
Review of the literature devoted to contemporary issues of antiepileptic therapy pregnant various drugs, identifying the most effective of them according to scientific publications from 2006 to 2016. (PUBMED, MEDline, The Cochrane Lb.) It is presents the current literature data on the frequency of occurrence of seizures in pregnant women, on the specifics of therapy with antiepileptic drugs (AEDs), the frequency of fetal malformations in pregnant women, taking AEDs regularly, and their dependence on the frequency, dosage and the nature of the therapy. Were studied according to the literature such AEDs as lamotrigine, phenytoin, carbamazepine, valproic acid, phenobarbital, as well as new drugs (vigabatrin, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin). It was found that the risk of birth defects in children observed in the application of high doses of drugs in polytherapy than with monotherapy. The studies revealed new data on the effect of psychotropic drugs on the fetus, allowing them to assess the ratio of "risk / benefit" and to develop recommendations on rational pharmacotherapy in pregnancy in recentyears. Keywords: epilepsy, pregnancy, antiepileptic drugs, teratogenicity.
Achieving a high quality of life for patients suffering from epilepsy, it is the primary task is not only to neurologists, but also for specialists in related disciplines, leading the
patient to the subsequent stages of treatment after exhibiting diagnosis [1]. Especially important is the improvement of the quality of life of patients with
epilepsy in the gestation period. As the literature suggests, 13% of women epileptic disease escalates during pregnancy [2], which is due to a decrease in the level of antiepileptic drugs (AEDs) in plasma due to the increased metabolism of pregnant [3]. Thus 14% of women seizures observed during pregnancy only [2]. According to foreign studies, aggravation of epilepsy during pregnancy occurs in about 10-13% women with 5% seizure frequency decreases from 85% - does not change [2].
According Lin H. et al. the study of the impact of seizures on fetal weight, gestational age and early preterm birth, direct relationship of seizures and the above pathology has been identified [4]. Developing cramps during pregnancy not only affect the course and outcome of pregnancy, but also in the heart of the fetus during pregnancy and childbirth, on the size, weight, rate of development, the child's cognitive functions. Thus, according to Ozdemir O. et al. the study of the impact of seizures on the fetus in the level of carbon dioxide in arterial umbilical blood was revealed that the fetus suffers a temporary asphyxia during a seizure. At the same time the authors, no association of seizures with cases of chronic hypoxia or prenatal asphyxia [5]. Thus, the presence aggravates epilepsy during pregnancy and childbirth, reduces the weight of the indicators and size of the fetus, gestational age, cognitive function, and therefore the study of the use of pharmacological correction of antiepileptic drugs will improve the above indicators [4,5].
According to the modern classification, AED are divided into the old - barbiturates and hydantoins, basic (most studied) - valproate and carbamazepine, intermediate -succinimides and benzodiazepines, as well as the new era that began in the 1990s, - topiramate, oxcarbazepine, lamotrigine, levetiracetam, pregabalin, felbamate, tiagabine, zonisamide [6].
As shown by recent studies, the application of AEDs is facilitated clinical seizures during pregnancy [7]. At the same time according to Vajda F. et al to assess the consequences in pregnant women who were not taking AEDs, it was found that when using AEDs before pregnancy clinic is facilitated by an epileptic fit during pregnancy. At the same time the use or abandonment of therapy during pregnancy, especially during the first trimester, the degree of malformations does not affect [7]. Other authors mark absence of congenital malformations in children when using AEDs. So, in pregnant women exposed to AEDs, 95.5% of children are born healthy among this population cohort [8].
As the study Bech B.et al. in 16% of cases among women using AEDs, develops spontaneous abortion [9]. At the same time, according to another study on the comparative safety assessment AEDs during pregnancy, through systematic review and meta-analysis found that in the treatment of AEDs may be congenital malformations, as well as the possible loss of the fetus, premature birth [9]. When studying the effects of actions on human placental probe cells on hormones and nutrients were identified lowering RNA cells bearing folic acid, when treated with valproic acid [9]. The authors have shown that further study of AEDs effect on placental barrier is the first step towards a more rational pharmacotherapy and adjunctive treatment of pregnant women with epilepsy [10]. When studying the genotype of the fetus it revealed that placental transport proteins differently directly protect the fetus from the negative effects of many drugs,
including the probe, sending back various received in pregnant xenobiotics [2].
As a result of years of research, it was found that the number of congenital malformations was significantly higher at AED polytherapy than with monotherapy [11,12]. At the same time in pregnancy monotherapy revealed 7.08% of cases of congenital malformations in polytherapy - 16.78% of the cases [12]. Rating incidence of congenital malformations in the treatment of epilepsy, according to K. Meador et al. it is recorded as follows: in the treatment of epilepsy, valproic acid, congenital malformations detected in 10.73% cases; phenytoin -7.36%, phenobarbital - 4.91%, carbamazepine - 4.62%, lamotrigine - 2.91% [12]. Results obtained by studies coordinated with research pharmacology dynamics of AEDs, as a result of which, it was found that phenytoin, levetiracetam, valproate and phenobarbital is likely to pass through the placental barrier to potentially clinically important amounts as gabapentin, topiramate, oxcarbazepine and lamotrigine are the placental barrier to potentially clinically small amount, perhaps, and reduces the risk of congenital malformations [13]. According to Ozdemir O. et al. therapy with phenytoin, carbamazepine, phenobarbital and lamotrigine increases the number of major malformations in two or three times compared with the general population, and the incidence of complications of valproate dose-dependent [11]. At the same time, AED, being a heterogeneous group on structure and mechanism of action, different effects, not only in the placenta [11], the level of cognitive function [14, 15], during pregnancy and childbirth [16], but also have different teratogenic activity [2,8,12]. Thus, Sveberg L. et al. in the course of the study EURAP, which involved 42 countries, 3784 women with epilepsy, we found that the proportion of pregnancies with abortion was significantly higher with valproate (75%), carbamazepine (67.35%), or phenobarbital (73.4%) than in pregnancies in women taking lamotrigine (58.2%) [16]. According Vajda F. et al. levetiracetam has a low teratogenic effects, namely in 0.7% cases, contributes to the development of birth defects and does not affect the intellectual development in children [17]. At the same time, as indicated by Garrity L. et al., levetiracetam is one of the most popular drugs in the treatment of epilepsy in pregnant women should be appointed in certain doses, relieves the attack, with the least negative effect on the fetus [18].
At the same time, according to Eadie M., valproate, too, is not recommended in the treatment, as it has a large list of side effects developing in the fetus [8]. The same opinion is shared by Tomson T., Battino D., alleging that the use of valproate in particular with doses above 800 mg / day increases the risk of teratogenicity [19]. It should be noted that the transition from the next AED is possible, however, such changes must be tested prior to conception [19].
Thus, it should be noted that congenital anomalies are more common with high doses of drugs and the number of simultaneously used [5,12]. An important role is played by genetic factors [3] When you select a drug for a particular patient is recommended to focus on its clinical efficacy. When this showed that lamotrigine and carbamazepine are among the most widely used AEDs, drugs are the safest [12,14,16,17] The incidence of congenital malformations in the background of these drugs is comparable to that of healthy mothers in some cases [8,17]. At the same time, valproic acid has a negative effect on the development of congenital
malformations as well as on the performance IQ of children [8,15]. Influence of probe of old and new generation during pregnancy and labor, the development rate in children is practically not been studied and
described in the available literature in isolated cases, often a controversial subject that is of great interest to the problem of antiepileptic therapy and in need of further research
СПИСОК ЛИТЕРАТУРЫ
1 Babenko M. V. To the question of life quality of patients with epilepsy// Meditsina i ekologiya.- 2012.- 3 (64).- P. 110-112.
2 Atkinson D., Brice-Bennett S. and D'Souza S. Antiepileptic Medication During Pregnancy: Does Fetal Genotype Affect Outcome?// Pediatr Res.- 2007.- 62(2).-P. 120-127
3 Sabers A. Seizure Control During Pregnancy.// Harden/Epilepsy in Women. - 2013. - №1. - P. 91-100
4 Lin H., Chen Y., Lin H.. No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs.// Journal of Neurology.- 2009.- 256(10).-P. 1742-1749
5 Ozdemir O., Sari M., Arpaci Ertugrul F., Kurt A., Selimova V. and Atalay C. The effects of a history of seizures during pregnancy on umbilical arterial blood gas values in pregnant women with epilepsy. //Journal of the Turkish German Gynecological Association. - 2014.- 15(3). - P.135-139
6 Spina E. Anticonvulsants.// Encyclopedia of Psychopharmacology.-2015.-P. 123-127
7 Vajda F., O'Brien T., Graham J., Lander C. and Eadie M.. The outcomes of pregnancy in women with untreated epilepsy. //Seizure.- 2015.- 24.-P. 77-81
8 Nakken, Lillestolen, Brodtkorb E. et al. Antiepileptic drugs and congenital malformations. //Tidsskr Nor Laegeforen. -2014.-134(12-13).- P. 1239-1242.
9 Tricco A., Cogo E., Angeliki V., Soobiah C., Hutton B., Hemmelgarn B., Moher D., Finkelstein Y. and Straus S.. Comparative safety of anti-epileptic drugs among infants and children exposed in utero or during breastfeeding: protocol for a systematic review and network meta-analysis.// Systematic Reviews.- 2014.- 3(1).- P. 68
10 Rubinchik-Stern M., Shmuel M. and Eyal S.. Antiepileptic drugs alter the expression of placental carriers: An in vitro study in a human placental cell line. // Epilepsia.- 2015.- 56(7).-P. 1023-1032
11 Ozdemir O., Sari M., Kurt A., Sakar V. and Atalay C.. Pregnancy outcome of 149 pregnancies in women with epilepsy: Experience from a tertiary care hospital.// Interventional Medicine and Applied Science. -2015.- 7(3).- P.108-113
12 Meador K., Reynolds M., Crean S., Fahrbach K. and Probst C.. Pregnancy outcomes in women with epilepsy: A systematic review and meta-analysis of published pregnancy registries and cohorts.// Epilepsy Research.- 2008.- 81(1).- P. 1-13
13 Harden C., Pennell P., Koppel B., Hovinga C., Gidal B., Meador K., Hopp J., Ting T., Hauser W., Thurman D., Kaplan P., Robinson J., French J., Wiebe S., Wilner A., Vazquez B., Holmes L., Krumholz A., Finnell R., Shafer P. and Le Guen C.. Practice Parameter update: Management issues for women with epilepsy--Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.// Neurology. -2009.- 73(2).- P. 142-149
14 Banach R., Boskovic R., Einarson T. and Koren G.. Long-Term Developmental Outcome of Children of Women with Epilepsy, Unexposed or Exposed Prenatally to Antiepileptic Drugs.// Drug Safety. - 2010. - 33(1).- P. 73-79
15 Meador K., Baker G., Browning N., Clayton-Smith J., Combs-Cantrell D., Cohen M., Kalayjian L., Kanner A., Liporace J., Pennell P., Privitera M. and Loring D. Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs. //New England Journal of Medicine. - 2009.- 360(16). - P. 1597-1605
16 Sveberg L., Svalheim S. and Tauboll E. The impact of seizures on pregnancy and delivery. //Seizure.- 2015.- 28.- P. 35-38
17 Vajda F., O'Brien T., Lander C., Graham J. and Eadie M.. The efficacy of the newer antiepileptic drugs in controlling seizures in pregnancy.// Epilepsia.- 2014.- 55(8).- P.1229-1234
18 Garrity L., Turner M. and Standridge S.. Increased Levetiracetam Clearance Associated with a Breakthrough Seizure in a Pregnant Patient Receiving Once/Day Extended-Release Levetiracetam. Pharmacotherapy.// The Journal of Human Pharmacology and Drug Therapy.- 2014.- 34(7). - P.128-132
19 Tomson T. and Battino D.. Pregnancy and epilepsy: what should we tell our patients? //Journal of Neurology.- 2009. -256(6). -P. 856-862
Т. Т. КИСПАЕВА, А. С. НУРАХМЕТОВА
Карагандинский государственный медицинский университет
ЭПИЛЕПСИЯ И БЕРЕМЕННОСТЬ: АНАЛИЗ ЭФФЕКТИВНОСТИ И ТЕРАТОГЕННОСТИ ПРОТИВОЭПИЛЕПТИЧЕСКИХ
ПРЕПАРАТОВ
Резюме: Обзор литературы посвящен современным вопросам противоэпилептической терапии беременных различными препаратами с выявлением наиболее эффективного из них по данным научных публикаций с 2006 по 2016 года. (PUBMED, MEDline, The Cochrane Lb.) Представлены современные литературные данные по частоте встречаемости судорожного синдрома у беременных, по особенностям терапии противоэпилептическими препаратами (ПЭП), по частоте внутриутробных пороков развития среди беременных, принимавшие регулярно ПЭП и их зависимость от частоты, дозировки и характера проводимой терапии. Были изучены по литературным данным такие ПЭП, как ламотриджин, фенитоин, карбамазепин, вальпроевая кислота, фенобарбитал,а также новые препараты (вигабатрин, габапентин, топирамат, тиагабин, окскарбазепин, леветирацетам, прегабалин). При этом было установлено, что риск развития врожденных пороков у детей наблюдаются при применении высоких доз препаратов при политерапии, чем при монотерапии. В исследованиях последних лет выявлены новые данные о влиянии психотропных препаратов на плод, позволяющие оценивать их соотношение «польза/риск» и разрабатывать рекомендации по рациональной фармакотерапии у беременных. Ключевые слова: эпилепсия, беременность, противоэпилептические препараты, тератогенность.
Т.Т. КИСПАЕВА, А.С. НУРАХМЕТОВА
Караганды мемлекеттШ медицина yHueepcumemi
ЭПИЛЕПСИЯ ЖЭНЕ ЖУКТ1Л1К: ЭПИЛЕПСИЯFА КДРСЫ ПРЕПАРАТТАРДЫН, ТИ1МД1Л1Г1 ЖЭНЕ
ТЕРАТОГЕНД1ПШН, ТАЛДАУЫ
ТYЙiн: Бул эдебиеттерге шолу 2006-2016 жылдардагы гылыми публикациялар бойынша ец тиiмдi нэтиже керсеткен препараттарды аны;тай отырып, ЖYKтi эйелдердщ эпилепсияга ;арсы терапиясыныц замандагы
мэселелерiне арналады. Жэне де ЖYктi эйелдерде кездесетiн устама синдромыныц жишп бойынша, эпилепсияга ;арсы препараттардыц терапия ерекшелiктерi бойынша, ЖYктi эйелдер арасында уры;тыц даму кемiстiгi, жиiлiгi бойынша, эпилепсияга ;арсы препараттарды тура;ты ;абылдаган ЖYктi эйелдердщ сол препараттарга тэуелдшп, препараттарды ;абылдаудыц жиiлiк сипаты бойынша жаца деректер берiлген. Бул эдебиет деректерi бойынша эпилепсияга ;арсы препараттар: ламотриджин, фенитоин, карбамазепин, вальпрой к;ышк;ылы, фенобарбитал жэне жаца препараттар: вигабатрин, габапентин, топирамат, тиагабин, окскарбазепин, леветирацетам, прегабалин сиякты препараттар бойынша деректер зерделендь Осы деректер бойынша монотерапияга ;араганда политерапияда препараттардыц мелшерден кеп дозасын ;абылдау кезiнде балаларда туа б^кен кем^тжтердщ кебеюi аны;талды. Соцгы жылдардагы зерттеулер нэтижесi психотропты препараттардыц уры;;а эсер ету женiнде жаца деректерiн аньщтады. Ол препараттардыц пайдасы немесе зияны ара- ;атынасын багалау MYмкiндiктерiн беруге жэне ЖYктi эйелдерге тиiмдi фармакотерапия бойынша жаца усыныстар эзiрлендi. ТYЙiндi сездер: эпилепсия, ЖYктiлiк, эпилепсияга ;арсы препараттар, тератогендiк
ЖИ1 ЕК1НШ1Л1К ПАРКИНСОНИЗМД1 ТУЫНДАТАТЫН ЭТИОЛОГИЯЛЫЦ АСПЕКТ1ЛЕР
Е.С.НУРГУЖАЕВ, А.Ш.ИЗБАСАРОВА, Т.М.ЗЕЙНОЛЛА
СЖ.Асфендияров атындагы Казац ¥лттыц медицина университетi Жуйке аурулары кафедрасы
УДК 616.831-005.4-036.12:616.839-08-073.
Баяндама мацсаты жас ерекшелжтерше байланысты Паркинсон синдромымен науцастарда жш кездесетш этиологиялыц аcnектiлердi аныцтау. Зерттеу барысында аурудыц кездесетт жас аралыгын, агъшын, цосымша ауруларды аныцтайтын анамнестикалыц эдс клиникалыц турт аныцтау арцылы неврологиялыц статусты багалау, Хен жэне Яр шкаласы бойынша цозгалысты багалау жэне математикалыц вцдеу эдicтерi цолданылды. Зерттеу нэтижеа Паркинсон синдромыныц жас ерекшелiктерiне байланысты кездесу ерекшелiктерiн кврcеттi жэне осы аурумен науцас адамдар арасында цантамырлыц фактор - 59 (59,26±5,2%) жастан асцан адамдар арасында Паркuнcонuзмдi дамытатын бiрiншiлiкэтиологиялыц фактор екен аныцталды. Tyürndi сездер: Паркинсон синдромы, Леви денешiктерi, цантамырлыц паркинсонизм, этиологиялыц аспектыер
бзекплт. Паркинсон синдромы-паллидо-нигралды; ЖYЙенiц за;ымдалуынан болатын YДемелi-нейродегенеративт синдром. Этиологиясы бойынша эртYрлi бузылыстар салдарынан булшы;еттердщ жогаргы тонусы, дiрiл жэне гипокинезиямен кершедь Ол этиологиясы бойынша эртYрлi за;ымданулардан пайда болады. Патология TYрiне байланысты кэнтамырлы;, постэнцефалитикалы; iсiктiк жэне паранеопластикалы; метаболикалы; гипоксиялы;, посттравмалы; уланудан болатын жэне токсикалы; TYрлерге жiктейдi [1]. Кантамырлы; паркинсонизмде Паркинсон синдромы барлы; TYрлерi арасында 3-6% кездеседi [2]. Ол жиi дисциркуляторлы энцефалопатиялар мен жартышарлардыц терец ;абаттарындагы а; заттыц диффузды ишемиялы; за;ымдалуынан болады. Кейде паркинсонизм церебралды атеросклероздар мен кардиогендi эмболдар себебiнен болатын етжа;ты инфаркт салдарынан болады. Кантамырлы; паркинсонизм жедел немесе созылмалы дамуы MYмкiн. Кантамырлы; паркинсонизмде клиникалы; керiнiстер жиi нау;ас
ая;тарында кeрiнедi. Журу мен тепе-тецщк бузылыстары аурудыц алгаш;ы сатысында-а; ай;ын бай;алады [3]. Аурудыц клиникалы; турш сипаттаганда дiрiлдi, дiрiлдi-ригидтi,
брадикинетикалы;-ригидт турлерш ажыратады. Сонымен ;атар, Хен жэне Яр шкаласы бойынша аурудыц дэрежес аньщталады: I дэрежелi паркинсонизм^ржа;ты симптоматика немесе гемипаркинсонизм, II дэрежелi паркинсонизм-еюжа;ты симптоматика, III дэрежелi турьеюжак;ты симптоматика жэне бiр;алыпты кeрiнiстi постуральдi тура;сызды;, IV дэрежесшде-;озгалыс белсендiлiгiнiц кеп мелшерде тежелуШра; ез еркiмен ;озгалыс MYMкiндiгiнiц болуымен жэне V дэрежесшде-нау;ас тесекке немесе MYгедектiк арбага тацылады. Ауруга эйелдермен салыстырганда ер адамдар жш шалдыгады [4, 5].
Аурудыц агымы арт;ан сайын брадифрения, созылмалы депрессия, интеллектуалды; бузылыстар, созылмалы делирий жэне торпидтшк бай;алады. Ауруды диагностикалау клиникалы; кeрiнiстерi мен талдаулар ар;ылы ЖYргiзiледi. Диагностиканыц
