Association of anti-emetic efficacy of Ondansetron with 18792A>G polymorphism in a drug target gene 5-HT3B in Pakistani population.

OBJECTIVE: To evaluate the association of anti-emetic efficacy of ondansetron with 18792A>G polymorphism in the target gene of 5-hydroxytryptamine type 3 subtype B. METHODS: The prospective clinical study was conducted at Combined Military Hospital, Rawalpindi and the genetic analysis was carried out at Institute of Biomedical and Genetic Engineering, Islamabad from August 2012 to September 2013. The subjects enrolled were undergoing elective laparoscopic cholecystectomy under general anaesthesia. All the patients were given anti-emetic ondansetron (4mg) intravenously 30 minutes before the end of surgery. Within the first two hours after surgery the response to ondansetron was noted down. Patients with the complaints of vomiting and those who had no vomiting were analysed for 18792A>G polymorphism using polymerase chain reaction- restriction fragment length polymorphism method. RESULTS: Of the 350 patients, 183(52%) had complaints of vomiting and 167(48%) had no such complaints. Overall, 195(56%) patients had 18792AA genotype, 130(37%) had genotype AG, and 25(7%) had GG genotype. No significant association was found between the incidence of vomiting and the 18792A>G genotypes at 2 hours after surgery (p>0.05). CONCLUSIONS: No association of anti-emetic efficacy of ondansetron with 18792A>G polymorphism in the target gene of 5-hydroxytryptamine type 3 subtype B was found.

Influence of genetic variations in ABCB1 on the clinical efficacy of ondansetron - A pharmacogenetic analysis of Pakistani population.

OBJECTIVE: To study the association of C1236T single-nucleotide polymorphisms of ABCB1 gene with non-responsiveness to antiemetic treatment in post-operative patients. METHODS: The prospective, clinical trial was conducted at Combined Military Hospital, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, in 2012-13, and comprised patients undergoing elective laparoscopic cholecystectomy. All patients were given 0.1 mg/kg ondansetron intravenously 30 minutes before the end of surgery and Deoxyribonucleic acid samples were obtained. The frequencies of genotypes of Single Nucleotide Polymorphism were determined by polymerase chain reaction followed by restriction fragment length polymorphism. RESULTS: Of the 426 patients, 201(47%) were responders having no nausea or vomiting, and 225(52.8%) were non-responders having nausea or vomiting. The incidence of post-operative nausea and vomiting during the first 2 hours after surgery was significantly lower in patients with 1236TT genotype than other 1236 genotypes (p<0.001). It was significantly higher in patients with CC genotype at 2 hours than other 1236 genotypes (p<0.001). CONCLUSIONS: Polymorphism of ABCB1 gene may be a good guide for predicting responsiveness for ondansetron.

Biochemical changes following succinylcholine administration after pretreatment with rocuronium at different intervals.

OBJECTIVE: To evaluate the biochemical changes associated with succinylcholine administration after pretreatment with rocuronium at different time intervals. METHOD: The prospective, randomised, single-blinded study was conducted at the Combined Military Hospital, Rawalpindi, from January to May 2010. Ninety male, aged 18-60 years, American Society of Anaesthesiology I or II patients undergoing elective inguinal herniotomy or external haemorrhoidectomy were included. The patients were randomly divided into three equal groups. Group A received a normal saline 5 ml as placebo 1 minute before succinylcholine; Group B received rocuronium 0.06 mg/kg 1 intravenously minute before succinylcholine, while Group C received intravenous injection of rocuronium 0.06 mg/kg 5 minute before succinylcholine. Venous blood samples for creatinine phosphokinase, lactate dehydrogenase and myoglobin plasma concentrations were obtained at 0, 30 minutes, 6 hours and 24 hours after succinylcholine administration. RESULTS: Mean serum creatinine phosphokinase and myoglobin concentrations were significantly decreased in Groups B and C compared to Group A at 30 minutes and 24 hours (p < 0.05). However, no significant difference in the enzyme levels at any time interval was observed among the rocuronium groups. There was a significant rise in lactate dehydrogenase concentrations at 6 hours and 24 hours in Group A compared to Groups B and C (p < 0.05). CONCLUSION: Pretreatment with rocuronium effectively reduces the biochemical changes associated with succinylcholine-induced muscle fasciculations. However, whether it is given 1 minute or 5 minutes before succinylcholine does not make much difference.

Effects of rocuronium pretreatment on muscle enzyme levels following succinylcholine.

Succinylcholine revolutionized anaesthetic practice by providing intense neuromuscular blockade of very rapid onset and ultrashort duration, thereby greatly easing the maneuver of tracheal intubation. However the worth of succinylcholine is limited by the frequent occurrence of muscular side effects which manifest biochemically in the form of rise in serum creatine kinase (CK). The administration of small doses of nondepolarizing muscle relaxants before the administration of succinylcholine has been shown to decrease the incidence and severity of muscular side effects experienced by the patients. This study was aimed at evaluating the efficacy of technique in reducing the muscular side effects of succinylcholine, biochemically manifested as rise in CK. Sixty healthy adults were enrolled in the study who were scheduled for minor muscle cutting surgeries under general anaesthesia. They were assigned at random to two groups of thirty patients each. They randomly received succinylcholine for intubation and a precurarization dose of rocuronium followed by succinylcholine for intubation. Blood samples were drawn for estimation of serum creatinine kinase. There was a significantly raised CK in the succinylcholine group. In the precurarization group the rise in CK was prevented and the levels were significantly less as compared to the group which received succinylcholine alone. Present study concluded that precurarization with rocuronium was effective in reducing the succinylcholine-induced rise in creatinine kinase.

Association of Anti-Emetic Efficacy of Ondansetron with G2677T Polymorphism in a Drug Transporter Gene ABCB1 in Pakistani Population.

OBJECTIVE: To determine the association of ABCB1 polymorphism G2677T with anti-emetic efficacy in patients treated with ondansetron for preventing postoperative nausea and vomiting. STUDY DESIGN: A clinical trial. PLACE AND DURATION OF STUDY: Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering, Islamabad, from 2012 to 2013. METHODOLOGY: Four mg ondansetron was administered intravenously 30 minutes before the end of surgery. A total of 246 patients with the complaints of nausea and vomiting and 244 patients without nausea and vomiting were analyzed for G2677T polymorphism using PCR-RFLP method. Results were described as frequency percentages and chi-square test with significance at p < 0.05. RESULTS: The patients with TT genotype had significantly lower incidence of postoperative nausea and vomiting during the first 2 hours (p < 0.001) and between 2 - 24 hours after surgery as compared to other genotypes (p < 0.001). The patients with GG genotypes had significantly higher incidence of this complaint (p=0.014). CONCLUSION: Polymorphism of ABCB1 has an association with responsiveness for ondansetron. There is a role for genetics in the management of PONV.