THE ROLE OF PHARMACOGENETICS IN INDIVIDUAL RESPONSE TO ANTIPARKINSONIAN DRUGS

Öz

Objective: Parkinson’s disease, the second most common neurodegenerative disorder after Alzheimer’s, is a progressive neurodegenerative disease characterized by tremor, rigidity, bradikinesis and postural instability. Environmental and genetic factors contribute to the pathophysiology of this disease. The pioneer of dopamine, L-DOPA, remains the gold standard of pharmacotherapy. Although current therapeutic options are clinically beneficial, since parkinson’s disease is a progressive disorder, all drugs used in treatment decline over time and increase in side effects.

Result and Discussion: Recent studies have shown that responses to antiparkinsonian drugs and their side effects exhibit significant interpersonal variability. Pharmacogenetics is a rapidly evolving and very promising field of research aiming to identify genetic markers associated with drug response. Studies in pharmacogenetics have shown that interpersonal genetic differences largely determine the response to drugs used to treat parkinson’s disease. Data obtained in this area will not only have the potential to present valuable therapeutic strategies for antiparkinson treatment, but also increase the probability of successful drug discovery. In this article, compiled studies to identify the role of genetic polymorphisms in better describing the variability in response to antiparkinson therapy and optimizing the pharmacotherapy of parkinson’s disease.

Anahtar Kelimeler

• Parkinson's disease
• dopamine
• pharmacogenetics
• polymorphism

ANTİPARKİNSON İLAÇLARINA VERİLEN BİREYSEL YANITTA FARMAKOGENETİĞİN ROLÜ

Öz

Amaç: Alzheimer hastalığından sonra ikinci en yaygın nörodejeneratif bozukluk olan Parkinson hastalığı, tremor, rijidite, bradikinezi ve postural instabilite ile karakterize ilerleyici bir nörodejeneratif hastalıktır. Çevresel ve genetik faktörler bu hastalığın patofizyolojisine katkıda bulunur. Dopaminin öncüsü olan L-DOPA, farmakoterapinin altın standardı olmaya devam etmektedir. Mevcut terapötik seçenekler klinik olarak faydalı olsa da parkinson hastalığı ilerleyici bir bozukluk olduğu için tedavisinde kullanılan tüm ilaçlarda zamanla etkinlik azalması ve yan etkilerde artış söz konusu olmaktadır.

Sonuç ve Tartışma: Son zamanlarda yapılan çalışmalardan elde edilen bulgular antiparkinson ilaçlara yanıtın ve yan etkilerin bireyler arası önemli değişkenlikler gösterdiğini işaret etmektedir. Farmakogenetik, ilaç yanıtı ile ilişkili genetik belirteçleri tanımlamayı amaçlayan, hızla gelişen ve çok umut verici bir araştırma alanıdır. Farmakogenetik alanında gerçekleştirilen araştırmalar, bireylerarası genetik farklılıkların parkinson hastalığının tedavisinde kullanılan ilaçlara yanıtı önemli ölçüde belirlediğini göstermiştir. Bu alanda elde edilen / edilecek veriler antiparkinson tedavide değerli terapötik stratejiler sunma potansiyelinin yanında başarılı ilaç keşfi ihtimalini de artıracaktır. Bu derlemede antiparkinson tedaviye yanıttaki değişkenliği daha iyi açıklamak ve parkinson hastalığının farmakoterapisini optimize etmek için genetik polimorfizmlerin rolünü tanımlamaya yönelik çalışmalar derlenmiştir.

Anahtar Kelimeler

• Parkinson hastalığı
• dopamin
• farmakogenetik
• polimorfizm

Kaynakça

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