Author/Editor		Dolžan, Vita; Kores-Plesničar, Blanka
Title		Genetski polimorfizem CYP2D6 in ekstrapiramidni stranski učinki antipsihotičnih zdravil
Translated title		CYP2D6 genetic polymorphism and extrapyramidal side effects of antipsychotic drugs
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 71, št. 7-8
Publication year		2002
Volume		str. 457-60
Language		slo
Abstract		Background. Antipsychotics and also some other psychiatric and some non-psychiatric drugs are known to cause extrapyramidal symptoms. Some of these synptoms, e.g. tardive dyskinesia, may be irreversible and may have an important influence on the quality of life. Various factors are involved in the etiopatogenesis of extrapyramidal symptoms are described by the authors, since the majority of antipsychotic drugs are metabolised through the CYP2D6 metabolic pathway. Various CYP2D6 phenotyping and genotyping methods and possible associations between genotype and phenotype are described, and in an overview of several clinical studies the results of some of them corroborate the role of genetic polymorphism in the emergence of extrapyramidal side effects of antipsychotic drugs, while in the others no association was observed. Conclusions. CYP2D6 genotype may not yet have a precise role in the extrapyramidal side effects of antipsychotic drugs, although it may indubitably be used to distinguish the patients with therapeutic problems caused by the changes in the metabolism of drugs that are substrates for CYP2D6 from these patients, who may have therapeutic problems caused by other mechanism of antipsychotic drugs activity. In this way the pharmacogenetics exerts an evermore important influence on a daily use of various drugs.
Summary		Izhodišča. Antipsihotična zdravila ter nekatera druga psihiatrična in nepsihiatrična zdravila povzročajo ekstrapiramidne simptome. Nekateri izmed njih, npr. tardivne diskinezije, so lahko ireverzibilni in pomembno vplivajo na kakovost življenja posameznikov. V njihovo etiopatogenezo so vključeni različni dejavniki. Avtorici v članku predstavljata genetski polimorfizem izoencima CYP2D6 in njegovo morebitno povezanost z nastankom ekstrapiramidnih simptomov, saj se prek izoencima CYP2D6 metabolizira večina antipsihotičnih zdravil. Predstavljene so metode fenotipizacije in genotipizacije CYP2D6, povezave med genotipom in fenotipom ter pregled nekaterih kliničnih študij, ki bodisi potrjujejo ali pa zanikajo vlogo genetskega polimorfizma v nastanku ekstrapiramidnih stranskih učinkov antipsihotičnih zdravil. Zaključki. Genotip ali fenotip CYP2D6 izoencima morda res še nimata natančno postavljene vloge v pojavnosti ekstrapiramidnih stranskih učinkov antipsihotičnih zdravil, nedvomno pa nujno poznavanje lahko pomaga pri ločitvi bolnikov, ki imajo terapevtske probleme zaradi spremenjene presnove zdravil, ki so substrati za CYP2D6, od tistih ki imajo terapevtske probleme zaradi drugih mehanizmov delovanja zdravil. Farmakogenetika tudi na ta način vse pomembneje vstopa v vaskodnevno uporabo zdravil.
Descriptors		SCHIZOPHRENIA ANTIPSYCHOTIC AGENTS POLYMORPHISM (GENETICS) EXTRAPYRAMIDAL TRACTS CYTOCHROME P-450 CYP2D6 ISOENZYMES PHENOTYPE GENOTYPE POLYMERASE CHAIN REACTION