Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

被引:11
|
作者
Lozupone, Madia [1 ]
Panza, Francesco [1 ,2 ,3 ,4 ]
Stella, Eleonora [5 ]
La Montagna, Maddalena [5 ]
Bisceglia, Paola [3 ,4 ]
Miscio, Giuseppe [6 ]
Galizia, Ilaria [5 ]
Daniele, Antonio [7 ]
di Mauro, Lazzaro [6 ]
Bellomo, Antonello [5 ]
Logroscino, Giancarlo [1 ,2 ]
Greco, Antonio [3 ,4 ]
Seripa, Davide [3 ,4 ]
机构
[1] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Unit Neurodegenerat Dis, Bari, Italy
[2] Univ Bari Aldo Moro, Dept Clin Res Neurol, Unit Neurodegenerat Dis, Pia Fdn Card G Panico, Tricase, Lecce, Italy
[3] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy
[4] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, Dept Med Sci, San Giovanni Rotondo, Italy
[5] Univ Foggia, Dept Clin & Expt Med, Psychiat Unit, Foggia, Italy
[6] IRCCS Casa Sollievo Sofferenza, Dept Clin Pathol, Lab Clin Chem, San Giovanni Rotondo, Italy
[7] Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy
关键词
Therapeutic failure; adverse drug reaction; psychiatric disorders; pharmacogenetics; cytochrome P450; CYP2D6; 5-hydroxytriptamine transporter; 5-HTT; dopamine transporter; DAT; ADVERSE DRUG-REACTIONS; TRANSPORTER GENE SLC6A4; SEROTONIN TRANSPORTER; CYTOCHROME-P450; 2D6; ALZHEIMERS-DISEASE; CYP2D6; POLYMORPHISM; NEUROPSYCHIATRIC SYMPTOMS; PLASMA-CONCENTRATIONS; METABOLIZING-ENZYMES; SERUM CONCENTRATIONS;
D O I
10.1080/17425255.2017.1246533
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients.Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as treatment effects mediated through targets (i.e., receptors in the brain) may also contribute to this image.Expert opinion: CYP genetics is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age. Furthermore, other specific polymorphic genes influence drug response through differential effects of their functional genetic variants. The known genotypes associated with an altered metabolizer status and drug transporters may help clinical decision-making to avoid concomitant treatments, reduce therapeutic attempts and increase drug safety in neuropsychiatric conditions in older age, after controlling for other clinical variables.
引用
收藏
页码:259 / 277
页数:19
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