scholarly journals The Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol

2019 ◽  
Vol 74 (3) ◽  
pp. 185-191
Author(s):  
Mikhail S. Zastrozhin ◽  
Valery V. Smirnov ◽  
Alexander S. Sorokin ◽  
Elena A. Grishina ◽  
Kristina A. Ryzhikova ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Depressive Disorder ◽  
Alcohol Dependence ◽  
Adverse Drug Reactions ◽  
Depressive Disorders ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Cyp2d6 Gene ◽  
Safety Indicator ◽  
Tetracyclic Antidepressants

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder, which adversely affects the prognosis of the course of both diseases. For the treatment of a depressive disorder, drugs from the group of tetracyclic antidepressants, of which mirtazapine is a representative, are used. Therapy with mirtazapine is associated with the risk of undesirable drug reactions and pharmacoresistance. Aim: To study the effect of CYPD6 isoenzyme activity on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism. Methods: The study was conducted on 109 Russian patients with a depressive disorder, comorbid with alcohol dependence. For the correction of depressive disorders within the framework of cyclothymia, mirtazapine was prescribed to patients at a dosage of 1545 mg/day. CYP2D6*4 genotyping (1846G A, rs3892097) was carried out using Real-time polymerase chain reaction with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of adverse drug reactions. Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.8; 5.0] (p0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p0.001). Conclusion: In this study, the effect of CYP2D6 gene polymorphism on the efficacy and safety of therapy with mirtazapine was demonstrated. Carrying a minor allele A is associated with an increased risk of adverse drug reactions, but improving performance profile performance.

scholarly journals Influence of CYP3A Activity on the Efficacy and Safety of Fluvoxamine in Patients Depressive Disorders and Comorbid Alcohol Use Disorder

2018 ◽  
Vol 73 (6) ◽  
pp. 411-419 ◽  
Author(s):  
Mikhail S. Zastrozhin ◽  
Valery V. Smirnov ◽  
Alexander S. Sorokin ◽  
Elena A. Grishina ◽  
Kristina A. Ryzhikova ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Depressive Disorders ◽  
Average Power ◽  
Inverse Correlation ◽  
Efficacy And Safety ◽  
Psychometric Scales ◽  
Safety Indicator ◽  
Endogenous Substrate ◽  
The Difference

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder (DD), which worsens adversely affects the prognosis of the course of both diseases and their outcomes. For the treatment of DD, drugs from the group of selective serotonin reuptake inhibitors, whose representative is fluvoxamine, are used. Fluvoxamine therapy is often associated with a risk of development is shown to be ineffective, and a part of patients develop dose-dependent adverse drug reactions (ADR) and pharmacoresistance.Objective: To study the effects of CYPD6 isoenzyme activity on the efficacy and safety of fluvoxamine therapy in patients with depressive disorders, comorbid with alcoholism.Methods: The study was conducted on 117 Russian patients with DD, alcohol-dependent comorbid. For the purpose of correction of depressive disorders within the framework of cyclothymia, fluvoxamine (Fevarin) was administered to patients at a dosage of 50−150 mg/day. Genotyping was carried out by the method of polymerase chain reaction in Real-time mode with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of ADR. To evaluate the activity of CYP2D6, the method of high performance liquid chromatography with mass spectrometry was used to measure the urinary content of the endogenous substrate of this isoenzyme and its metabolite, the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline.Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was statistically significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.0; 5.0] (p0.001); safety indicator, estimated on a UKU scale: 3.0 [2.0; 4.0], (GA) 4.0 [4.0; 4.2] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.0] (p0.001); safety indicator, estimated on a UKU scale: (GG) 9.0 [9.0; 10.0], (GA) 6.0 [6.0; 7.0] (p0.001). The calculation of the correlation coefficients between the difference in the number of scores on psychometric scales and the metabolic ratio showed a statistically significant inverse correlation of the average power degree between the efficiency index estimated by the HAMD scale (r=-0.467, p0.05). There was no connection with the difference on the UKU scale (r=0.173, p0.05).Conclusion: In a study of a group of 117 patients with DD, comorbid with alcohol dependence, the effect of CYP2D6 activity, estimated by the ratio of the endogenous substrate concentrations of pinolin and its metabolite 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, on the efficacy of fluvoxamine therapy. This effect was also shown using the results of genotyping. The results of genotyping also showed the existence of a difference in the safety index in patients with different genotypes from the polymorphic marker CYP2D6 1846GA.

scholarly journals MicroRNA hsa-miR-370-3p is a new biomarker for assessing the level of CYP2D6 gene expression, as well as the clinical efficacy and safety of mirtazapine in patients with depressive disorders comorbid with alcohol use disorder

2020 ◽  
pp. 62-63
Author(s):  
М.С. Застрожин ◽  
В.Ю. Скрябин ◽  
Е.А. Гришина ◽  
К.А. Рыжикова ◽  
И.В. Буре ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Concentration ◽  
Gene Polymorphism ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Alcohol Use Disorder ◽  
Depressive Disorders ◽  
Polymorphic Marker ◽  
Efficacy And Safety ◽  
Cyp2d6 Gene

Проведено изучение влияния полиморфизма гена CYP2D6 на эффективность и безопасность терапии миртазапина у пациентов с депрессивными расстройствами, коморбидными с алкоголизмом. В группе из 106 пациентов с депрессивными расстройствами, коморбидными с алкогольной зависимостью, было продемонстрировано влияние полиморфизма 1846G>A гена CYP2D6 (rs3892097) на показатели профиля безопасности миртазапина, но не эффективности. При этом hsa-miR-370-3p остается перспективным биомаркером оценки уровня экспресии гена CYP2D6, так как уровень его плазменной концентрации отличался у носителей разных генотипов по полиморфному маркеру 1846G>A, хотя и не обнаружилась связь с клинической эффективностью и безопасностью. The study of the effect of CYP2D6 gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism was carried out. In a group of 106 patients with depressive disorders comorbid with alcohol dependence, the effect of the 1846G> A polymorphism of the CYP2D6 gene (rs3892097) on the safety profile of mirtazapine was demonstrated, but not on the effectiveness. At the same time, hsa-miR-370-3p remains a promising biomarker for assessing the level of CYP2D6 gene expression, since the level of its plasma concentration differed in carriers of different genotypes for the polymorphic marker 1846G> A, although no connection with clinical efficacy and safety was found.

Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael Zastrozhin ◽  
Valentin Skryabin ◽  
Valeriy Smirnov ◽  
Anastasiya Zastrozhina ◽  
Elena Grishina ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Genetic Polymorphism ◽  
Depressive Disorder ◽  
Efficacy And Safety ◽  
Major Depressive ◽  
Cyp2d6 Gene

scholarly journals Efficacy and safety of selamectin of flea infestation in dags

2018 ◽  
Vol 53 (1) ◽  
pp. 78
Author(s):  
S. SOTIRAKI (Σ. ΣΩΤΗΡΑΚΗ) ◽  
C. HIMONAS (Χ. ΧΕΙΜΩΝΑΣ) ◽  
P. DEBOUCK ◽  
G. BITSAS (Γ. ΜΠΙΤΖΑΣ)
Keyword(s):  
Adverse Drug Reactions ◽  
Clinical Signs ◽  
Untreated Group ◽  
Field Conditions ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Flea Infestation ◽  
Highly Effective ◽  
Monthly Dose ◽  
Adult Flea

The study was conducted at three dog shekers in Thessaloniki Greece, το confirm die efficacy and safety of selamectin aτ a minimum dosage of 6 mg/kg adminisτered topically as a monthly dose repeaτed three times in die treatment of natural i n f l a t i o n s of Ctenocephalides spp. Twenty (20) dogs, with confirmed naturally acquired flea inflations, were enrolled in die sttidy as primary patiems. All animals completed the study on day 90. Twenty-two in cornai dogs were also treated but not evaluated for efficacy (secondary patiems). There was no untreated group. Only one live adult flea was recovered on only one animal on study day 30, a reduction of die geomettical mean of 99.7 % (p < 0.0001) compared to the sτarτ of die study. Dead fleas were found on 3 animals aτ day 30 (1 or 2 per animal). No live or dead fleas were found on day 60 or on day 90. Ατ sttidy beginning on Day 0, seventy percem of sttidy animals had various clinical signs of flea inflation. These signs gradually decreased and by die end of die sttidy on day 90, only one animal remained widi a score of 1, indicating a low imensity in a single area of die body. All odier animals were free of clinical signs. No abnormal clinical signs or suspend adverse drug reactions were observed after treatment of die 20 primary or die 22 secondary patiems. The daτa collected confirm that under field conditions diree consecutive mondily doses of selamectin are highly effective and safe in die treatment and comrol of fleas in dogs.

scholarly journals Comparative evaluation of efficacy and safety of methotrexate either alone or in combination with hydroxychloroquine in patients suffering from rheumatoid arthritis

2017 ◽  
Vol 6 (8) ◽  
pp. 1996
Author(s):  
Amanjot Kaur ◽  
Shakti B. Dutta ◽  
Amandeep Singh ◽  
Amit Varma ◽  
Mirza A. Beg ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Adverse Drug Reactions ◽  
Positive Family History ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Intergroup Comparison ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Background: Rheumatoid arthritis (RA) a chronic autoimmune inflammatory disease and Methotrexate being widely used as monotherapy and in combination for the treatment of RA. Combination therapy provides additional or even more potentiating effects, therefore have been widely used. This study is aimed at comparing the efficacy and safety of Methotrexate either alone or in combination.Methods: This study was conducted for one year from 1st January to 31st December 2015. 52 patients diagnosed with RA were included in this study and were divided in two groups, Group-1 (n=29) patients received methotrexate (MTX) 7.5-15mg/week and Group-2 (n=23) patients received methotrexate 7.5mg once a week + Hydroxychloroquine (HCQ) 200mg twice daily. The patients were followed up for a period of 16 weeks. Statistical analysis was done by using graph pad insta and p value of <0.05 was considered significant.Results: A total of 52 patients were included in the study. The mean age of patients was 50.53±14.81 years. 43 (82.69%) patients were females and 9 (17.30%) were males. 23 (44.23%) patients had positive family history of the disease. The Rheumatoid factor was positive in 42 (80.70%) and anti-CCP was raised in 50 (96.15%) patients. The RAPID-3 and DAS-28 scores on intragroup comparison was highly significant (p <0.0001) and the intergroup comparison was significant (p <0.01) between baseline and 16 weeks in both the groups. The improvement in inflammatory marker CRP was highly significant on intragroup (p <0.0001) and intergroup (p<0.001) comparison between baseline and 16 weeks in both the groups. The mean changes in Vitamin-D3 between baseline and at 16 weeks were insignificant (p >0.05) in both the groups. Total of Adverse drug reactions reported were 42 (50.60%) in group-1 and 41 (49.40%) in group-2.Conclusions: The combination therapy was found to be more efficacious than MTX monotherapy in improving symptoms and quality of life. The adverse drug reactions were mild, more in combination therapy and none of the patients required withdrawal of treatment.

scholarly journals Charms & Harms: Noni

2010 ◽  
Vol 2 (3) ◽  
pp. 254
Author(s):  
Felicity Goodyear-Smith
Keyword(s):  
Adverse Drug Reactions ◽  
Health Professionals ◽  
Herbal Medicines ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Pharmaceutical Quality ◽  
Wide Range ◽  
Suspected Adverse Drug Reactions

SUMMARY MESSAGE: Evidence for the efficacy of noni for the wide range of medicinal purposes for which it may be used is not available. Health professionals should be aware of the possibility of (undisclosed) use of noni and its use should be avoided, or at least used only with caution, in patients on warfarin. Suspected adverse drug reactions should be reported to CARM. As with all herbal medicines, different noni products vary in their pharmaceutical quality, and the implications of this for efficacy and safety should be considered.

scholarly journals Pleiotropic features of dihydropyridine calcium channel antagonists

2014 ◽  
Vol 11 (3) ◽  
pp. 81-83
Author(s):  
G S Anikin
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Adverse Drug Reactions ◽  
Calcium Ions ◽  
Modern Medicine ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Calcium Channel Antagonists ◽  
Lipophilic Compound

It is hard to imagine modern medicine without safe drugs (D). Often, adverse drug reactions (ADR) are the reason for drug with drawal, which is quite effective as a whole. The main dihydropyridine calcium channel antagonists (DCCA) ADR are the edema of shin and tachycardia, causing this drug with drawal. Lercanidipine is aquite new member of this class; it is a highly lipophilic compound, which blocking the influx of calcium ions through L-type calcium channels, by maintaining the high intramembrane concentration. This review provides the data on the efficacy and safety of lercanidipine and its pleiotropic features.

Comparative Study of Incadronate and Elcatonin in Patients with Malignancy-Associated Hypercalcaemia

2002 ◽  
Vol 30 (3) ◽  
pp. 230-243 ◽  
Author(s):  
T Matsumoto ◽  
N Nagata ◽  
N Horikoshi ◽  
I Adachi ◽  
Y Ohashi ◽  
...  
Keyword(s):  
Comparative Study ◽  
Adverse Drug Reactions ◽  
Serum Calcium ◽  
Intravenous Infusion ◽  
Rapid Onset ◽  
Clinical Usefulness ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Intramuscular Injections ◽  
Disturbance Of Consciousness

The clinical usefulness of incadronate was compared with elcatonin in 26 patients with malignancy-associated hypercalcaemia. Data from 21 and 24 patients could be used to assess efficacy and safety, respectively. Eleven patients were given a single 10-mg intravenous infusion of incadronate and 10 received twice-daily intramuscular injections of 40 IU of elcatonin for 7 consecutive days. After treatment, corrected serum calcium levels decreased significantly in both groups. The anti-hypercalcaemic effect of elcatonin was characterized by its rapid onset, with serum calcium levels reduced 1 day after administration. In contrast, the anti-hypercalcaemic effect of incadronate was more sustained but only became apparent a few days after infusion. Evaluation of symptoms revealed significantly greater improvement rates in the incadronate group compared with the elcatonin group. Adverse drug reactions were observed in three patients in the incadronate group, i.e. mild and transient fever in two cases and exacerbation of disturbance of consciousness in one case. These findings suggest that incadronate produces more marked and sustained hypocalcaemic effects than elcatonin, and that co-administration of these two drugs may yield both rapid and sustained control of malignancy-associated hypercalcaemia.

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome

2020 ◽  
pp. 001857872093175
Author(s):  
Valentin Yurievich Skryabin ◽  
Mikhail Zastrozhin ◽  
Marco Torrado ◽  
Elena Grishina ◽  
Kristina Ryzhikova ◽  
...  
Keyword(s):  
Steady State ◽  
Genetic Polymorphisms ◽  
Adverse Drug Reactions ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Steady State Concentration ◽  
State Concentration

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 − 806C>T genotypes: (*1/*1) −12.0 [−15.0; −8.0], (*1/*17+*17/*17) −7.0 [−14.0; −5.0], P < .001, as well as the results of TDM: ( CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P < .001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.

scholarly journals Aldosterone antagonists in cardiology practice

2019 ◽  
Vol 17 (2) ◽  
pp. 73-77
Author(s):  
Andrey I. Danilov ◽  
Sergey N. Kozlov ◽  
Andrey V. Evseev
Keyword(s):  
Clinical Pharmacology ◽  
Adverse Drug Reactions ◽  
Lower Risk ◽  
Adverse Reactions ◽  
Kidney Injury ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Aldosterone Antagonists ◽  
Drug Of Choice ◽  
Wide Range

In review presents the patological effects of aldosterone, clinical pharmacology of aldosterone antagonists and their role in countering the development of cardiovascular diseases are highlighted. The results of clinical studies have demonstrated high clinical efficacy and safety of spironolactone and eplerenone in a wide range of cardiovascular risk. However, the potential adverse drug reactions associated with these drugs limit their use in some categories of patients. However, adequate monitoring of these reactions, including hyperkalemia and acute kidney injury, can be avoided. In situations where there are indications for the use of spironolactone or eplerenone, the latter is the drug of choice due to the lower risk of gender adverse reactions. The frequency of other adverse drug reactions, in particular hyperkalemia, spironolactone and eplerenone are comparable.

Sign in / Sign up

Export Citation Format

Share Document