Gebelikte Antiepileptik İlaçların Kullanımının Değerlendirilmesi

Abstract

Gebelikte önceden var olan ve/veya gebelik sırasında oluşan hastalıklar sebebiyle ilaç kullanımı gerekli olabilmektedir. Gebelikte tedavisine devam edilmesi gereken hastalıklardan biri de epilepsidir. Gebelerde epilepsi görülme insidansı %0,5 ile 1 arasında değişmekte olup, bu süreçte başta tonik-klonik olmak üzere bütün nöbet tiplerinin engellenmesi gerekmektedir. Çünkü bu dönemde geçirilecek nöbetler, hem anneye hem de bebeğe zarar verebilmektedir. Öte yandan epilepsinin tedavisinde kullanılan antiepileptik ilaçların da teratojenite potansiyellerinin yüksek olduğu bilinmektedir. Kardiyak defektler, damak ve dudak yarıkları, hipospadias ve nöral tüp defekti kullanımlarına bağlı en sık görülen malformasyonlardandır ve bu malformasyonların oluşma riski politerapiyle birlikte artmaktadır. Bu derlemede, gebelikte sıklıkla kullanılan antiepileptik ilaçların teratojenite potansiyelleri değerlendirilmiştir.

Keywords

• teratojenite,gebelik,antiepileptik

Assessment of Usage the Antiepileptic Drugs During Pregnancy

Abstract

During pregnancy medications can be used due to pregnancy related problems or existing diseases of the pregnant woman. Epilepsy is one of these diseases that the treatment should be continued during pregnancy. Among pregnant women incidence of epilepsy ranges between 0.5 % and 1 %. During pregnancy, all type of seizures including tonic-clonic type should be prevented. Because of these seizures both the mother and the baby fetus might be damaged. On the other hand, it is known that antiepileptic drugs used in the treatment of epilepsy have a high potential for teratogenicity. Cardiac defects, cleft lip and palate, hypospadias, neural tube defects are common malformations caused by antiepileptic drug usage and risk of having these malformations increase with polytherapy. In this review, teratogenetic potentials of most commonly used antiepileptic drugs during pregnancy are evaluated.

Keywords

• teratogenicity,pregnancy,antiepileptic

References

1. Costantine, M.M.: Physiologic and pharmacokinetic changes in pregnancy, Front Pharmacol, 5(65), 1-5 (2014).
2. Atasü, T., Öçer, F. (Eds.), Gebelikte Fetusa ve Yenidoğana Zararlı Etkenler, İstanbul, Nobel Tıp Kitapevleri, (2000), 2. Baskı.
3. Gebelik ve Emzirme Döneminde İlaç Kullanımı. http://www.e-kutuphane.teb.org.tr/pdf/mised/ kasim05/8.pdf
4. Türk Epilepsi ile Savaş Derneği. http://www.turkepilepsi.org.tr (26.03.2016)
5. Conway, J.M., Birnbaum A.K., ‘’Drugs for Epilepsy’’, Finkel, R., Panavelil, T. A., Whalen, K. (Eds.), Lippincott Illustrated Reviews: Pharmacology, Phileadelphia, Wolters Kluwer, (2015),157- 170.
6. Ciğer, D.A.: Gebelik ve Epilepsi, Kadın Doğum Dergisi, 6, 1336-1340 (2007)
7. Hart, L.A., Sibai, B.M.: Seizures in pregnancy: epilepsy, eclampsia, and stroke, Semin Perinatol, 37(4), 207-224 (2013)
8. Erten, N., Erişgin Z.: Gebelikte Epilepsi Tedavisinde Yeni Nesil Antiepileptik İlaçlar, Harran Üniversitesi Tıp Fakültesi Dergisi, 11(3), 297-303 (2014)

9. Loebstein, R., Lalkin, A., Koren, G.: Pharmacokinetic changes during pregnancy and their clinical relevance, Clinical Pharmacokinetics, 33(5), 328-343 (1997)
10. Shılalukey, K., Koren, G., ‘’Special Considerations in the Pregnant Patient’’, Clinical Toxicology, Philadelphia, W.B. Saunders Company, (2001), 101-110.
11. Thornburg, K.L., Bagby, S.P., Giraud, G.D., ‘’Maternal Adaptations to Pregnancy’’, Plant, T. M., Zeleznik A.J., (Eds.), Knobil and Neill’s Physiology of Reproduction, San Diego, Academic Press, (2015), 4th Edition, 1927-1955.
12. Kayaalp, S.O., Dalkara, T., ’’Antiepileptik İlaçlar’’, Kayaalp S.O. (Ed.), Akılcı Tedavi Yönünden Tıbbi Farmakoloji, Ankara, Ertem Basım, (2012), 13. baskı, 2. cilt, 917-934.
13. Gambone, J.C., Moore, J.G., Hacker N.F.C., Obstetrik ve Jinekolojinin Temelleri, İstanbul, Nobel Tıp Kitapevleri, (2009), 4. baskı.
14. Öztürk, Z.: İlaç Kullanan Gebeye Yaklaşım: Teratojenite Riski ve Danışmanlık Hizmeti, Sted, 23(5), 201-205 (2014)
15. T.C. Sağlık Bakanlığı Acil Sağlık Hizmetleri Genel Müdürlüğü. http://www.acilafet.gov.tr/ teratojenite-merkezi/ (21.04.2016)
16. Orer, H. S., ‘’Teratojen Ajanlar’’, Ayhan, A., Bozdağ, G., Deren, Ö., Durukan, T., Esinler, İ., Günalp, S. ve diğ. (Eds.), Temel Kadın Hastalıkları ve Doğum Bilgisi, Ankara, Güneş Tıp Kitapevleri, (2014), 1706-1709).
17. Freyer, A.M.: Drug-prescribing challenges during pregnancy, Obstetrics, Gynaecology & Reproductive Medicine, 18(7), 180-186 (2008)
18. Johannessen L.C., Larsson, P.G., Rytter, E., Johannessen, S.I.: Antiepileptic drugs in epilepsy and other disorders-A population-based study of prescriptions, Epilepsy Research, 87(1), 31-39 (2009)
19. Cotterman-Hart, S., ‘’Antiepileptic Drugs: First Generation’’, Newton, H.B., Maschio, M. (Eds.), Epilepsy and Brain Tumors, Boston, Academic Press, (2015), 159-169.
20. Cotterman-Hart, S., ‘’Antiepileptic Drugs: Second and Third Generation’’, Newton, H.B., Maschio, M. (Eds.), Epilepsy and Brain Tumors, Boston, Academic Press, (2015), 171-193.
21. Erdal, A., Demir, A. B., Baykan, B., Akpınar, Ç. K., Demet, K., Aykutlu, E. ve diğerleri, Epilepsi Çalışma Grubu Tanı ve Tedavi Rehberi, Türk Nöroloji Derneği, (2015)
22. Başoğlu, M., Epilepsiler, İstanbul, Akal Ofset, (2001).
23. Lasoń, W., Dudra-Jastrzębska, M., Rejdak, K., Czuczwar, S.J.: Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update, Pharmacological Reports, 63(2), 271-292 (2011)
24. McNamara, J.O., ‘’Pharmacotherapy of the Epilepsy’’, Brunton, L. L., Chabner, B.A., Knollmann, B.C. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, USA, The McGraw- Hill, 12th Edition, 583-606.
25. Cascino, G.D., Sirven, J.I. (Eds.), Adult Epilepsy, UK, John Wiley & Sons Ltd, (2011).
26. Stefan, H., Feuerstein T.J.: Novel anticonvulsant drugs, Pharmacology & therapeutics, 113, 165- 183, (2007)
27. Antiepileptik ilaçlar. http://yunus.hacettepe.edu.tr/~ucalis/PDF/C13_old.pdf (23.04.2016)
28. John, G., Basic Neurology, New York , McGraw-Hill, (2000), 3rd Edition.
29. Leach, J.P., ‘’Antiepileptic Drug Therapy’’, Aminoff , M.J., Daroff, R.B. (Eds.), Encyclopedia of the Neurological Sciences, Oxford, Academic Press, (2014), 2nd Edition, 224-232.
30. Katzung, B.G., Masters S.B., Trevor A.J., ‘‘Antiseizure drugs‘‘, Basic & Clinical Pharmacology, Singapore, The McGraw-Hill, (2012), 12th Edition, 403-427.
31. Epilepsi. http://www.itfnoroloji.org/epilepsi/Epilepsi.htm (11.04.2016)
32. Browne, T. R., Holmes, G. L., Epilepsi El Kitabı, Ankara, Güneş Tıp Kitapevleri, (2013), 4. Baskı.
33. Perucca, P., Gilliam, F.G.: Adverse effects of antiepileptic drugs, The Lancet Neurology, 11(9), 792- 802 (2012)
34. Holmes, L.B. , Hernandez-Diaz, S.: Newer anticonvulsants: Lamotrigine, topiramate and gabapentin, Birth Defects Research Part A - Clinical and Molecular Teratology, 94(8), 599-606 (2012)
35. Harden, C. L., Thomas, S.V., Tomson T., Epilepsy in Women, UK, Wiley- Blackwell, (2013).
36. Vanlı Yavuz, E. N., Baykan, B.: Epilepsi Tedavisinde Güncel Yaklaşımlar, Klinik Gelişim Dergisi, 26(1), 39-43 (2013).
37. Reuber, M., Schachter, S. C., Elger C. E., Altrup U., Açıklamalı Epilepsi, İstanbul, Nobel Tıp Kitapevleri, (2012).
38. Ataklı, D., Ezelsoy, B., Arpaci, B.: Gebelik ve Epilepsi, Klinik Psikofarmakoloji Bülteni, 3(1-2), 72-77 (1993)
39. Pennell, P.B., Gidal, B.E., Sabers, A., Gordon, J., Perucca, E.: Pharmacology of antiepileptic drugs during pregnancy and lactation, Epilepsy & Behavior, 11(3), 263-269 (2007)
40. Pennell, P.B., Hovinga, C.A.: Antiepileptic Drug Therapy in Pregnancy I: Gestation‐Induced Effects on AED Pharmacokinetics, International Review of Neurobiology, 83, 227-240 (2008)
41. Tomson, T., Battino, D.: Teratogenic effects of antiepileptic drugs, Lancet Neurol, 11(9), 803-813 (2012)
42. Inselman, A.L., Hansen, D.K., ‘’Phenytoin’’, Encyclopedia of Toxicology, Oxford, Academic Press, (2014), 3rd Edition, 895-897.
43. Hansen, D.K., ‘’Developmental Toxicity of Antiepileptic Drugs’’, McQueen, C.A. (Ed.), Comprehensive Toxicology, Oxford, Elsevier, (2010), 2nd Edition, 177-187.
44. Voinescu, P.E., Pennell, P.B.: Management of epilepsy during pregnancy, Expert Rev Neurother, 15(10), 1171-1187 (2015)
45. Chambers, C., Schaefer, C., ‘’Epilepsy and antiepileptic medications’’, Drugs During Pregnancy and Lactation, San Diego, Academic Press, (2015), 3rd Edition, 251-291.
46. Lo, J.C.Y., ‘’Carbamazepine’’, Encyclopedia of Toxicology, Oxford, Academic Press, (2014), 3rd Edition, 665-667.
47. Williams, S.H., Kehr, H.A.: An update in the treatment of neurologic disorders during pregnancy- focus on migraines and seizures, J Pharm Pract, 25(3), 341-351 (2012)
48. Chung, S.S., Schusse, C., ‘‘Antiepileptic drugs’’, Aronson J. K. (Ed.), Side Effects of Drugs Annual, (2014), 35, 133-169.
49. FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children http://www.fda. gov/downloads/Drugs/DrugSafety/UCM350748.pdf (03.04.2016)
50. Chateauvieux, S., Morceau, F., Diederich, M., ‘‘Valproic Acid’’, Encyclopedia of Toxicology, Oxford, Academic Press, (2014), 3rd Edition, 905-908.
51. Wlodarczyk, B.J., Palacios, A.M., George, T.M., Finnell, R.H.: Antiepileptic drugs and pregnancy outcomes, American Journal of Medical Genetics Part A, 158A(8), 2071-2090 (2012)
52. Ataklı, D.: Gebelik ve Epilepsi, Epilepsi, 8(2), 113-119 (2002)
53. FDA Drug Safety and Availability: Questions and Answers: Risk of oral clefts (cleft lip and/or palate) in infants born to mothers taking Topamax (Topiramate) http://www.fda.gov/drugs/drugsafety/ ucm245470.htm (30.03.2016)
54. Çetin, M.: Gebelikte Psikotrop İlaç Kullanımı: Bir Güncelleme, Bulletin of Clinical Psychopharmacology, 21(2), 161-173 (2011)
55. Cassina, M., Dilaghi, A., Di Gianantonio, E., Cesari, E., De Santis, M., Mannaioni, G.ve diğerleri: Pregnancy outcome in women exposed to antiepileptic drugs: Teratogenic role of maternal epilepsy and its pharmacologic treatment, Reproductive Toxicology, 39, 50-57 (2013)
56. Bayrak, M., Bozdağ, H., Karadağ C., Günay, T., Göynümer, G.: Epilepsi Tanılı Gebelerde Obstetrik ve Perinatal Sonuçların Retrospektif Analizi, İKSST Dergisi, 6(3), 127-132 (2014)
57. Clinical Revıew: Second Review of Prenatal Valproic Acid Exposure and Neurodevelopmental Delay pediatricadvisorycommittee/ucm234486.pdf (18.04.2016)