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Titolo:
Pharmacogenetics and psychopharmacotherapy
Autore:
Poolsup, N; Po, ALW; Knight, TL;
Indirizzi:
Aston Univ, Ctr Evidence Based Pharmacotherapy, Birmingham B4 7EQ, W Midlands, England Aston Univ Birmingham W Midlands England B4 7EQ 7EQ, W Midlands, England
Titolo Testata:
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
fascicolo: 3, volume: 25, anno: 2000,
pagine: 197 - 220
SICI:
0269-4727(200006)25:3<197:PAP>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEPHENYTOIN HYDROXYLATION PHENOTYPES; SPARTEINE OXIDATION POLYMORPHISM; DRUG-METABOLISM POLYMORPHISM; HALOPERIDOL PLASMA-LEVELS; S-MEPHENYTOIN; GENETIC-POLYMORPHISM; DEBRISOQUINE OXIDATION; PSYCHIATRIC-PATIENTS; CYTOCHROME-P450 ENZYMES; CLINICAL IMPLICATIONS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
164
Recensione:
Indirizzi per estratti:
Indirizzo: Po, ALW Aston Univ, Ctr Evidence Based Pharmacotherapy, Aston Triangle, BirminghamB4 7EQ, W Midlands, England Aston Univ Aston Triangle Birmingham W Midlands England B4 7EQ and
Citazione:
N. Poolsup et al., "Pharmacogenetics and psychopharmacotherapy", J CLIN PH T, 25(3), 2000, pp. 197-220

Abstract

Response to drugs can vary between individuals and between different ethnic populations. The biological (age, gender, disease and genetics), culturaland environmental factors which contribute to these variations are considered in this review. The most important aspect is the genetic variability between individuals in their ability to metabolize drugs due to expression of'polymorphic' enzymes. Polymorphism enables division of individuals withina given population into at least two groups, poor metabolisers (PMs) and extensive metabolisers (EMs) of certain drugs. The two most extensively studied genetic polymorphisms are those involvingcytochrome P450 2D6 (CYP2D6) and CYP2C19. CYP2D6 metabolizes a number of antidepressants, antipsychotics, beta-adrenoceptor blockers, and antiarrhythmic drugs. About 7% of Caucasians and 1% of Asians are PMs of CYP2D6 substrates. CYP2C19 enzyme participates in the metabolism of omeprazole, propranolol and psychotropic drugs such as hexobarbital, diazepam, citalopram, imipramine, clomipramine and amitriptyline. The incidence of PMs of CYP2C19 substrates is much higher in Asians (15-30%) than in Caucasians (3-6%). Variations in metabolism of psychotropic drugs result in variations in their pharmacokinetic parameters. This may lead to clinically significant intra- and inter-ethnic differences in pharmacological responses. Such variations are discussed in this review. Differential receptor-mediated response may play a role in ethnic differences in responses to antipsychotics and tricyclic antidepressants, but such pharmacodynamic factors remain to be systematically investigated. The results of studies of ethnic differences in response to psychopharmacotherapy appear to be discrepant, most probably due to limitations of study design, small sample size, inadequately defined study sample, and lack of control of confounding factors. The clinical value of understanding pharmacogenetics is in its use to optimize therapeutic efficacy, to prevent toxicity of those drugs whose metabolism is catalysed by polymorphic isoenzymes, and to contribute to the rational design of new drugs. Finally, applications and impact of pharmacogenetics in the field of psychopharmacotherapy are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 22:16:53