1.Research advance in CYP2D6 genetic polymorphism and pharmacogenomics
Tianwei DONG ; Shuang WANG ; Jun YANG ; Zhiguo ZHANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(3):343-346
CYP2D6 genetic polymorphism results in individual difference of therapeutic effect and adverse reaction of related drugs this article made an overview for that.
2.Effects of hydromorphone in prevention of shivering after spinal anesthesia
Tianwei ZHANG ; Qumin CHEN ; Min ZHOU ; Yingwei DONG
Chinese Journal of General Practitioners 2017;16(6):462-465
Eighty patients(American Society of AnesthesiologistsⅠ-Ⅱ)scheduled for elective unilateral inguinal hernia surgery with spinal anesthesia between January and June 2016 were randomized into two groups with 40 in each group.Patients were intravenously injected with normal saline (5 ml) in control group or hydromorphone 5 μg/kg (diluted to 5 ml) in intervention group after spinal anesthesia.Tympanic temperature and the incidence of shrivering were measured before and after spinal anesthesia at predetermined intervals.Side effects during surgery and the first 48 h after surgery were recorded.Rescue drug tramadol 0.5 mg/kg was given intravenously to patients with grade ≥2 shivering for more than 5 min duration.Tympanic temperature decreased significantly compared to the baseline from 20 min in control group and from 10 min in intervention group after spinal blocking(P<0.05),while there were no significant differences in tympanic temperature at the same time points between two groups(P>0.05).The incidence of shivering was significantly lower in intervention group [17.5%(7/40)] than that in control group [47.5%(19/40),χ2=8.205,P=0.004].The incidence of nausea and vomiting was 5.0%(2/40)in intervention group and 0.0% (0/40) in control group (χ2=2.051,P=0.494).The incidence of sedation was not significantly different between control group [0.0%(0/40)] and intervention group[10.0%(4/10),χ2=4.211,P=0.116].The use of rescue tramadol was more frequently in control group [32.5%(13/40)] than that in intervention group [7.5%(3/40),χ2=7.812,P=0.01].The results indicate that intravenous hydromorphone can significantly attenuate the incidence of shivering after spinal anesthesia for inguinal herniorrhaphy repair surgery with minimum side effects.
3.Therapeutic effect of bisoprolol with gene targeting therapy for hypertension
Tianwei DONG ; Shuang WANG ; Libo WANG ; Leiyi ZHANG ; Zhiguo ZHANG ; Lili LEI ; Jun YANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(5):523-526
Objective:To explore therapeutic effect of bisoprolol with CYP2D6 and CYP3A4 gene targeting therapy for hypertension .Methods :A total of 100 cases with essential hypertension (EH) were selected ,among them 20 ca-ses were randomly chosen to receive routine medication (bisoprolol 5 mg/d ,routine treatment group ) ,the other 80 patients were equally divided into group A (CYP2D6*10) and group B (CYP3A4*1G) .According to detection results of CYP2D6*10 and CYP3A4*1G gene polymorphism ,they were dived into group ACC (n=13) ,group ACT (n=14) ,group ATT (n=10) ,group BCC (n=21) ,group BCT (n=17) and group BTT (n=0) .Bisoprolol dosage was adjusted according to genotypes :group ACC and group BCC received 10 mg/d ,group ACT and group BCT received 5 mg/d ,group ATT and group BTT received 2.5 mg/d .Blood drug concentration ,blood pressure and heart rate were compared among above groups after two weeks .Relationship between plasma concentration of bisoprolol and gene polymorphism of drug metabolism enzyme was evaluated .Results:Comparison between related groups with same bi-soprolol dosage :there were no significant difference in blood drug concentration ,heart rate and blood pressure be-tween ACT and routine treatment group , P>0.05 all;compared with routine treatment group ,there was significant rise in blood drug concentration [ (33.5 ± 19.1) ng/ml vs .(50.13 ± 23.21) ng/ml] ,significant reduction in heart rate [ (71.4 ± 5.16) times/min vs .(66.5 ± 6.04) times/min] and blood pressure [ (127.22 ± 10.44/82.4 ± 7.27) mmHg vs .(119.48 ± 11.97/71.2 ± 10.30) mmHg] in BCT group , P<0.05 all .Conclusion:Because gene possesses polymorphism ,therapeutic effect of bisoprolol treating hypertension is differing ;the gene targeting therapy may significantly improve therapeutic effect for hypertension .
4.Relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension
Jun YANG ; Shuang WANG ; Tianwei DONG ; Libo WANG ; Leiyi ZHANG ; Zhiguo ZHANG ; Lili LEI
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(2):155-160
Objective: To study the relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension. Methods: A total of 60 patients with essential hypertension (EH) received metoprolol 47.5mg/d for 3d. After 3d the plasma metoprolol concentration after oral 2h was measured. Polymorphism of CYP2D6*10 gene was detected by PCR-RFLP. According to results of gene detection, the patients were divided into CC genotype group (wild type homozygote, fast metabolism type, n=14), CT genotype group (heterozygous mutation, intermediate metabolism type, n=25) and TT genotype group (homozygous mutation, slow metabolism, n=19). Metoprolol dosage was adjusted according to CYP2D6*10 genotype. After one week, plasma concentration of metoprolol after oral 2h was measured again, and mean heart rate and blood pressure were measured before and after gene-directed therapy. Results: Before gene-directed therapy, compared with CC and CT group there was significant increase in plasma concentration of metoprolol [(26.57±19.40) ng/ml vs. (23.88±12.86) ng/ml vs. (64.74±32.94) ng/ml, P<0.01] in TT group; compared with TT group, there were significant rise in mean systolic blood pressure [mSBP, (132.84±13.40) mmHg vs. (144.14±14.28) mmHg], mean diastolic blood pressure [mDBP, (76.95±9.07) mmHg vs. (81.36±7.33) mmHg] and mean heart rate [mHR, (69.13±11.83) times/min vs. (76.66±7.33) times/min] in CC group, P<0.05 all. After gene-directed therapy, there were no significant difference in plasma concentration of metoprolol, mSBP, mDBP and mHR among all groups, P>0.05 all; Compared with before gene-directed therapy, there was significant increase in plasma concentration of metoprolol, and significant decrease in mSBP, mDBP and mHR in CC group (P<0.05). There were no significant difference in blood pressure and heart rate between before and after treatment in CT group and TT group (P>0.05). Conclusion: CYP2D6*10 gene polymorphism affects metoprolol metabolism and its therapeutic effect on hypertension, gene-directed therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.