CYP3A4 activity and haloperidol effects in alcohol addicts

Zastrozhin, M. S.; Смирнов, В. В.; Сычев, Д. А.; Savchenko, L. M.; Bryun, Evgeny А.; Matis, O.A.

doi:10.3233/jrs-150676

Cited by 8 publications

(6 citation statements)

References 3 publications

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“…In our previous works, we showed the effect of CYP2D6 polymorphism (and its activity)21 and the activity of CYP3A428 on haloperidol efficacy and safety.…”

Section: Discussionmentioning

confidence: 98%

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

Застрожин¹,

Brodyansky²,

Skryabin³

et al. 2017

PGPM

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BackgroundAntipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described.ObjectiveThe objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methodsThe study included 64 male patients (average age 41.38 ± 10.14 years, median age 40 years, lower quintile [LQ] 35 years, upper quintile [UQ] 49 years). Bio-Rad CFX Manager™ software and “SNP-Screen” sets of “Syntol” (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and rs2863170. In every “SNP-Screen” set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels.ResultsResults of this study detected a statistically significant difference in the adverse drug reaction intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 ± 2.24 (10/10) versus 13 ± 2.37 (9/10; p < 0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 ± 1.59 (10/10) versus 6.41 ± 1.33 (9/10; p = 0.006) were revealed.ConclusionPolymorphism of the SCL6A3 gene can affect the safety of haloperidol, and this should be taken into account during the choice of drug and its dosage regimen.

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“…In our previous works, we showed the effect of CYP2D6 polymorphism (and its activity)21 and the activity of CYP3A428 on haloperidol efficacy and safety.…”

Section: Discussionmentioning

confidence: 98%

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

Застрожин¹,

Brodyansky²,

Skryabin³

et al. 2017

PGPM

View full text Add to dashboard Cite

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“…Other risk factors for dystonia are male gender, black race, hypocalcaemia, hypoparathyroidism and dehydration 1. There is also a higher risk of extrapyramidal symptoms (EPS) in alcohol addicts due to the same metabolism pathway via cytochrome P450 7. Nevertheless, there is no sufficient data for ‘binge drinking’ consumers.…”

Section: Discussionmentioning

confidence: 99%

Involuntary movements in an adolescent: what are the causes?

et al. 2019

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Involuntary movements can be a troublesome condition and represent a real challenge for emergency doctors, particularly for patients of paediatric age. We report a case of a 17-year-old boy with painful involuntary movements mostly affecting his mouth and lower limbs, but also the trunk. After reviewing the patient’s history, it was revealed that the adolescent had had acute alcohol intoxication with severe acute agitation and therefore was given a single dose of 10 mg intravenous haloperidol. The concealment of the recent event posed serious difficulties in reaching the diagnosis. When the diagnosis of haloperidol-induced acute dystonia was made, 3 mg of intravenous biperiden was promptly administered with complete clinical resolution in 15 min.

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“…Since previous research demonstrated that CYP3A4 and CYP3A5 have common substrates 21,22 and that endogenous cortisol transforms to 6-beta-hydroxicortisol (6-b-HC) selectively by CYP3A isoenzyme, the metabolic ratio of 6-b-HC/ cortisol in urine can be used to evaluate the activity of CYP3A. 23 In our study, to evaluate CYP3A enzymatic activity, we determined the urinary concentration of endogenous substrate of the enzyme and its metabolite, 6-b-HC to cortisol ratio, [24][25][26][27][28] using high-performance liquid chromatographymass spectrometry (HPLC-MS/MS). [29][30][31] The results of the isoenzymes evaluation are demonstrated in arbitrary units.…”

Section: Phenotypingmentioning

confidence: 99%

Using the CYP3A Activity Evaluation to Predict the Efficacy and Safety of Diazepam in Patients With Alcohol Withdrawal Syndrome

Skryabin¹,

Застрожин

Grishina

et al. 2021

Journal of Pharmacy Practice

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Background: Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on the efficacy and safety of diazepam therapy. Objective: The objective of our study was to study the effect of CYP3A isoenzymes activity on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg / day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP3A4 C>T intron 6 ( rs35599367) genotypes: ( CC) −9.0 [−13.0; −5.0], ( CT+TT) −13.5 [−15.0; −10.0], p = 0.014. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: ( CC) 7.5 [6.0; 11.0], ( CT+TT) 11.0 [8.0; 12.0], p = 0.003. Conclusion: Possible relationship between the CYP3A activity, evaluated by the content of the urinary endogenous substrate of the given isoenzyme and its metabolite, the 6-beta-hydroxy cortisol (6-β-HC) / cortisol ratio, and the efficacy of diazepam was demonstrated. This possible relationship was also supported by the genotyping results. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of pharmacoresistance.

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CYP3A4 activity and haloperidol effects in alcohol addicts

Cited by 8 publications

References 3 publications

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

Involuntary movements in an adolescent: what are the causes?

Using the CYP3A Activity Evaluation to Predict the Efficacy and Safety of Diazepam in Patients With Alcohol Withdrawal Syndrome

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