Assessment of cardiac parameters after the administration of nicorandil before primary percutaneous coronary intervention.

Objective: To assess cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes and major adverse cardiac events after treatment with nicorandil before primary percutaneous coronary intervention. METHODS: The comparative, analytical study was conducted from October to November 2022 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Rawalpindi Institute of Cardiology, Rawalpindi. The sample comprised ST-elevated myocardial infarction patients of either gender aged at least 30 years with an ejection fraction of at least 35% undergoing primary percutaneous coronary intervention. Participants were selected based on the above-mentioned inclusion and informed consent was taken before their enrolment in this research study. The sample was randomised into control group A receiving conventional acute coronary syndrome treatment, and intervention group B receiving nicorandil in addition to the conventional treatment. Cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes, and major adverse cardiac events noted and compared. Data was analysed using SPSS 26. RESULTS: Of the 140 patients, 70(50%) were in each of the 2 groups. In group B, 60(85.7%) patients achieved a completely settled ST segment on electrocardiogram compared to 25(35.7%) in group A (p=0.001). There was a significant inter-group difference with respect to cardiac troponin I value 6 hours after percutaneous coronary intervention and major adverse cardiac events (p<0.05), but creatine kinase-myocardial band level was no significantly different between the groups (p=0.761). Conclusion: Prophylactic use of nicorandil in ST-elevated myocardial infarction patients decreased the incidence of reperfusion injury.

Early initiation of Dapagliflozin and its effect on health related quality of life in acute heart failure: a randomised controlled trial.

OBJECTIVE: To determine the role of dapagliflozin in improving functional status and health-related quality of life in acute heart failure cases. METHODS: The prospective, randomised controlled study was conducted from July 2022 to January 2023 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Armed Forces Institute of Cardiology, Rawalpindi, and comprised hospitalised adult patients of either gender with acute heart failure. They were randomised into two equal groups, with intervention group A receiving oral dapagliflozin 10mg daily in addition to conventional therapy, and with control group B receiving conventional therapy alone. Health-related quality of life was assessed using Kansas City Cardiomyopathy Questionnaire. Improvement in functional status was assessed by New York Heart Association functional classification. Data was obtained at baseline and after 12-week follow-up. Data was compared using SPSS 26. RESULTS: Of the 150 patients, 75(50%) were group A; 62(82.66%) males and 13(17.3%) females with mean age 63.76±10.05 years. There were 75(50%) patients in group B; 60(80%) males and 15(20%) females with mean age 66.13±11.73 years (p>0.05). The study was completed by 73(97.3%) in group A and 69(92%) in group B. The Kansas City Cardiomyopathy Questionnaire scores improved post-intervention compared to baseline values (p<0.001) in both groups. Group A showed comparatively greater improvement in health status compared to group B (p<0.05). CONCLUSIONS: Early initiation of dapagliflozin in patients admitted with acute heart failure was found to be associated with rapid and significant improvement in health and functional status. Clinical Trial Link: https://www.irct.ir. RCT No. (IRCT20220529055013N).

Pharmacogenetic Basis of Response Fluctuations to Methotrexate in Rheumatoid Arthritis: A Narrative Review.

Rheumatoid arthritis is a crippling autoimmune disease affecting more than 18 million people worldwide and thus becoming one of the important contributors to the global health burden. The majority of the affected are females, especially those above the age of 50, but males and younger adults are equally vulnerable. It is a constellation of genetic and environmental factors that interplay to manifest the joint deformities and disabilities that are the hallmarks of this disease. Painkillers are used alongside disease-modifying anti-rheumatic drugs to minimize the patient's agony and also to halt the progression of the disease. Worldwide, methotrexate is recommended as the first-line drug, but unexpected resistance is encountered in a significant number of patients. This review summarizes the pathophysiology, clinical findings, and therapeutic strategies for rheumatoid with a focus on research studies performed to establish a genetic basis for response fluctuations of methotrexate across different population groups.

Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.

OBJECTIVE: To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. METHODS: The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27. RESULTS: Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B. CONCLUSIONS: Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration. Clinical Trial Number: Iranian Registry of Clinical Trials: IRCT20221207056738N1.

The effect of Dapagliflozin on renal functions in hospitalized patients with Acute Heart Failure.

Objective: To evaluate the influence of dapagliflozin on renal functions and diuretics use in patients with acute heart failure (AHF). Methods: This comparative analytical study was conducted at Armed Forces Institute of Cardiology, Rawalpindi from July 2022 to November 2022. Patients were distributed equally in two groups i.e. Dapagliflozin and Conventional Groups, where patients received dapagliflozin added to conventional therapy for AHF and, only conventional therapy for AHF respectively. Estimated glomerular filtration rate (eGFR), serum creatinine were measured and compared on admission, after 48 hours and on discharge. Weight loss during hospitalization, daily dose of furosemide and length of hospital stay was also recorded. Quantitative parameters were analyzed using t-test or Mann Whitney U test accordingly. Results: There were no significant baseline differences in renal functions. A modest decline in eGFR was observed in both groups after 48 hours. However, the variation in values of eGFR remained similar among both groups after 48 hours (p-value 0.365) and on discharge (p-value 0.768). Whereas, patients subjected to dapagliflozin treatment exhibited a more profound diuretic response expressed as greater weight loss (p-value < 0.001), achieved at comparatively lower doses of loop diuretics. Moreover, they also had a shorter duration of hospital stay (six vs eight days, p-value <0.001). Conclusion: Institution of dapagliflozin did not cause any significant deterioration of renal functions, whereas; it was associated with improved diuretic response as depicted by more pronounced weight loss at comparatively lower doses of loop diuretics.

Optimizing The Daily Units Of Insulin; Insulin Degludec Aspart Versus Premixed Insulin Aspart In The Standard Of Care Regimen For Type 2 Diabetics.

BACKGROUND: This study aimed to evaluate the impact of Insulin Degludec Aspart on daily insulin dose in comparison with premixed insulin aspart. METHODS: It was a Quasi-Experimental study conducted in the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi and the Department of Medicine, Pak Emirates Military Hospital, Rawalpindi. One hundred and twenty participants with documented type 2 diabetes, taking premixed insulin aspart therapy were enrolled in the study. Sixty participants were substituted with insulin degludec aspart from premixed insulin aspart. Daily units of insulin were recorded for 12 weeks and compared for both groups. SPSS version 26 was used for analysing the study results. RESULTS: Participants of the insulin degludec aspart group showed a significant reduction in the daily insulin dose compared to the premixed insulin aspart group. Fifty-two units per day were administered in the participants of the premixed insulin aspart patients while insulin degludec aspart participants received 40 units of median daily insulin dose (p-value<0.001). CONCLUSIONS: Insulin degludec aspart proved superior to premixed insulin aspart in a reduction in the daily dose of insulin with insulin degludec aspart.

Pharmacokinetics and bioavailability of tocotrienols in healthy human volunteers: a systematic review.

OBJECTIVE: To evaluate and compare the pharmacokinetic parameters, especially bioavailability, of annatto-based tocotrienol with palm tocotrienol-rich fraction in healthy human volunteers for better therapeutic outcome. METHODS: The systematic review was conducted between April and August 2021 in accordance with the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines, and comprised search on PubMed, Google Scholar, Pakmedinet and Google search engines for open-label or double-blind randomised controlled trials involving healthy human volunteers published till January 2021. Key words used included annatto-based tocotrienol, palm tocotrienol-rich fraction, absorption and bioavailability. Boolean operators were also used, like tocotrienol AND bioavailability, annatto tocotrienol AND pharmacokinetics. RESULTS: Of the 230 articles identified, 50(21.7%) articles met the eligibility criteria. Of them, 7(14%) were selected for data extraction and detailed analysis. Pharmacokinetic parameters of annatto-based tocotrienol were better than palm-derived tocotrienol. Oral administration of all the isomers of annatto-based tocotrienols resulted in dose-dependent increase in area under curve and plasma levels. Amongst all the isomers of annatto-based and palm-derived tocotrienol, delta isomer of annatto-based tocotrienol had the highest bioavailability with area under curve 7450±89 ng/ml, time to reach peak plasma levels 4 hours, maximum plasma concentration 1591±43 ng/nl and elimination half-life 2. 68 ±0.29 hrs. Pharmacokinetic parameters of delta isomer of annatto-based tocotrienol was greater than palm tocotrienol-rich fraction. CONCLUSIONS: Bioavailability of annatto-based tocotrienol was better than that of palm-derived tocotrienol-rich fraction. Delta isomer of annatto-based tocotrienol had the highest bioavailability amongst all isomers of tocotrienol.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

Efficacy And Cost-Effectiveness, Comparison Of 7-Days Vonoprazan Versus 14-Days Esomeprazole Based Triple Therapies For Treating Helicobacter Pylori Infection In Pakistani Population: A Randomized Clinical Trial.

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients. Methods: This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed. Results: The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group. Conclusion: One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results.

Evaluation Of Anti-Inflammatory Efficacy Of Ascorbic Acid After Third Molar Surgery.

BACKGROUND: Abstraction of wisdom teeth or impacted third molar under local anaesthesia is one of the most frequent interventions by an oral and maxillofacial surgeon. The abstraction of the third molar is usually followed by the release of liberation and consequent trismus, pain, and swelling due to the area of the third molar being highly vascularized and rich in loose connective tissue. Objective of the study was to evaluate the anti-inflammatory effect of ascorbic acid following surgical extraction of the third molar. METHODS: The current study was carried out Armed Forces Institute of Dentistry, Rawalpindi, from October to December 2022. This was a cross-sectional observational study. Fifty participants who required surgical extraction of the impacted third molar were included in the study via non-probability purposive sampling and were segregated equally into two groups, i.e., Group A and Group B, comprising twenty-five participants in each group. Group A received amoxicillin with clavulanic acid (625 mg) thrice a day and metronidazole (400 mg) twice daily. In comparison, Group B received amoxicillin with clavulanic acid (625 mg) thrice daily, ascorbic acid (500 mg) twice daily, and metronidazole (400 mg) twice daily. Both groups received naproxen sodium as per requirement (550 mg). Pain, facial swelling, and C reactive protein concentration were evaluated until the 7th postoperative day. RESULTS: There was a reduction in pain and facial swelling in both groups, but in the ascorbic acid group, there was more reduction in pain and facial swelling compared to the control group. However, the difference between the two groups in reducing pain and facial swelling was statistically significant (p<0.01). There was a reduction in CRP in both groups, but in the ascorbic acid group, there was more reduction in CRP 2.35 (1.60-5.30) compared to the control group 2.6 (0.86-5.03). However, the difference between the two groups in reducing C reactive protein concentration was statistically insignificant (p>0.05). CONCLUSIONS: Our study concluded that ascorbic acid significantly reduced inflammation and C reactive protein, so ascorbic acid should be used as an adjuvant supplement with other conventional drugs.

Effect Of Sglt2 Inhibitor Dapagliflozin On Sodium, Potassium And Creatinine Levels In Patients With Acute Heart Failure.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a new class of medication for the treatment of type 2 diabetes mellitus. Additionally, they have been found to have beneficial effects on heart failure outcomes, convincingly reducing the morbidity and mortality in heart failure. Although the medical data indicates SGLT2i to be safe and cardio-protective, very little attention has been given to the impact of these agents on electrolyte balance particularly in acute heart failure (AHF). We aimed to evaluate the effect of SGLT2i, and dapagliflozin on serum sodium, potassium and creatinine in AHF. Methods: Overall, 160 adult patients of either gender, admitted with AHF were selected for the study. Selected individuals were randomly assigned to receive dapagliflozin 10 mg orally added to standard medical treatment (n=80) or were in reception of standard medical therapy only (n=80). Serum electrolytes and serum creatinine were collected on admission and day 7 or on discharge whichever happened earlier. Results: The mean level of serum electrolytes displayed insignificant differences among both groups on admission. The mean level of serum potassium was higher in the dapagliflozin group compared with the control group (p<0.001) on day 7/discharge. Mean serum sodium level was comparable and showed significant differences between the two groups following treatment (p-value=0.021). Significant higher levels of serum creatinine were observed following treatment in both groups. However, on intergroup comparison, they were statistically insignificant. Conclusion: Dapagliflozin is an effective treatment of heart failure and is not associated with deterioration of serum electrolyte levels and renal functioning when used as add-on therapy in AHF.

Role Of Granisetron In Minimising Use Of Meperidine As A Rescue Drug For Post Spinal Shivering.

BACKGROUND: Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous detrimental effects on the human body. Hence, its management becomes imperative. Meperidine, an opioid analgesic, is the drug of choice for this condition. However, the use of meperidine is controversial, as it carries the devastating adverse effect of respiratory depression. We explored the role of granisetron, a 5HT3 antagonist and a commonly used antiemetic premedication, in minimising the incidence of post-spinal shivering and decreasing the use of meperidine as a rescue drug. METHODS: Overall, 160 parturient patients, between the ages 18-50, undergoing uncomplicated, elective caesarean section, were enrolled in the study, and randomized into two groups with 80 participants each: Group A received 3ml of normal saline, and Group B was administered 3 mg granisetron,15 minutes before spinal anaesthesia institution. Incidence of clinically relevant shivering (score of 3 or more) was noted, and it was recorded whether meperidine was used or not. RESULTS: 67.5% of participants in Group A, and 32.5% of patients in Group B, experienced clinically relevant shivering, with 62.5% of patients in Group A and 28.75% in Group B warranting the use of meperidine. There was a statistically significant difference between the two groups in terms of incidence of clinically relevant shivering, and meperidine consumption (p-value <0.001). CONCLUSIONS: Premedication with 3 mg granisetron effectively attenuates the occurrence of post-spinal shivering and, hence, lowers the requirement of meperidine as rescue medication.

Granisetron versus Ondansetron: Comparison of 5HT3 antagonists in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients.

Objectives: To evaluate and compare the Ondansetron and Granisetron in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients. Methods: The comparative analytical study was conducted at Combined Military Hospital, Rawalpindi, from September to October, 2021. One hundred and twenty pregnant women undergoing cesarean section, were enrolled in the study via non probability convenience sampling, and divided into three groups containing 40 participants each based on the type of antiemetic premedication they received, if any: Group N were those not requiring antiemetic premedication, Group O consisted of those given ondansetron 4mg, and Group G had those receiving 3mg granisetron, 15 minutes prior to administration of spinal anaesthesia. Systolic blood pressures and heart rates were recorded before and at multiple intervals after spinal anaesthesia was administered. Episodes of hypotension and bradycardia were recorded. Requirement of phenylephrine and atropine as rescue drugs was recorded for each participant. Results: There was a statistically significant difference in incidence of hypotension among the three groups (p value <0.001), with both drugs being superior to the control group (p value <0.001 for both), and 3mg granisetron being superior to 4mg ondansetron (p value <0.001). As for incidence of bradycardia, ondansetron and granisetron were superior to control group (p value 0.03 and <0.001 respectively), but there was no significant difference between the two drug groups (p value 0.094). Conclusion: High dose granisetron (3mg) is superior to low dose ondansetron (4mg) in preventing hemodynamic fluctuations induced by spinal anaesthesia.

Role of lidocaine and its effect on postoperative outcomes in abdominal cholecystectomy.

OBJECTIVE: To investigate the role of pre- and intra-operative lidocaine infusion on post-operative pain management. METHODS: The interventional, prospective study was conducted from September 2019 to June 2020 at the Pakistan Ordnance Factories Hospital, Wah Cantt, Pakistan, and comprised patients aged 18-60 years undergoing elective cholecystectomy who were randomised into intervention group A and control group B. Group A was given a bolus dose of lidocaine hydrochloride 2 mg/kg in addition to the standard anaesthesia protocol, while group B was given continuous intravenous infusion of 0.9% normal saline along with the standard protocol. Blood samples for interleukins 6 and 8 were taken at baseline, and then at 2, 6 and 8 hours Post-operatively. Data was analysed using SPSS 23. RESULTS: Of the 40 patients, 20(50%) were in each of the two groups. There was a marked decrease in interleukins 6 and 8 levels group A compared to group B (p<0.05). Interleukin 8 level showed a marked decline compared to that of interleukin 6 (p<0.05). CONCLUSIONS: A decrease in interleukins 6 and 8 levels highlighted the anti-inflammatory role of lidocaine and resulted in a decrease in post-operative opioid consumption.

Association between intestinal helminthic infections and anaemia status in preschool children in the district Skardu of Pakistan.

OBJECTIVE: To evaluate the frequency of parasitic infections and to assess the relation between intestinal helminth infection and the anaemia status of pre-school children. METHODS: The community-based cross-sectional study was conducted in Skardu, Pakistan, from August 2016 to January 2017, and comprised pre-school children of either gender. Demographical data was collected using a structured questionnaire. Stool samples were collected and examined for the presence and differentiation of ova / larvae of different intestinal helminths under microscope at the pathology department of a local healthcare facility. Blood haemoglobin was measured from blood samples and anaemia was defined as blood Hb <11g/dL. Data was analysed using SPSS 22. RESULTS: Of the 300 paediatric subjects, 169 (56.3%) were males and 131 (43.7%) females. The overall mean age of the sample was 36±16 months. Of the total, 161(53.67%) were found infected. Among the infected, 93(31%) were males and 68(22.67%) were females (p=0.10). Among those who were infection-free, 46(15.3%) children were anaemic. CONCLUSIONS: Prevalence of helminthic infections in pre-school children in Skardu was found to be high. The public health problem needs to be addressed for the healthy development of children.

Protective Effects Of Trimetazidine Against Doxorubicin-Induced Cardiotoxicity And Hepatotoxicity In Mice.

BACKGROUND: Trimetazidine (TMZ) is traditionally known for cardio protection, however various experimental studies are also evaluating its protective benefits in other tissues. Doxorubicin (DOX) is an extensively used chemotherapeutic drug but is associated with a high incidence of multi-organ damage. This study was aimed at countering DOX induced cardiac and hepatic toxicity by administering TMZ in two different study designs. METHODS: It was a laboratory based randomized controlled trial conducted on 40 BALB/c mice divided into 5 groups (n=8). In the two study designs conducted, TMZ in a dose of 10 mg/kg was given orally for five and ten consecutive days. On the third and eighth day of the respective designs, 10 mg/kg DOX was administered intraperitoneally. RESULTS: DOX induced significant elevation of four biochemical markers, namely creatine kinase MB (CKMB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (p-value ≤0.0001). Histological changes in heart were graded to be moderate while hepatic changes were graded as mild. Trimetazidine administration for ten days attenuated the enzyme upsurge significantly with p-value ≤0.05 for ALT and ≤0.0001 for AST, LDH and CKMB. However, five-day TMZ administration caused nonsignificant restoration in ALT and CKMB level (p-value >0.05). Hepatic and cardiac histological changes were restored accordingly in both groups. CONCLUSIONS: Treatment with TMZ for ten days, seven of which were prior to DOX administration, was concluded to be an effective strategy to counter cardiac and hepatic toxicity of DOX.

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.

Mini Review - Analysis of Artemether and Dihydroartemisinin by high performance high liquid chromatography in biological fluids-issues and solutions.

Artemether-Lumefantrine is the most widely recommended antimalarial combination used to treat millions of patients suffering from malaria. Artemether undergoes rapid metabolism and gets converted to its active metabolite dihydroartemisisn. Drug analysis is a vital aspect to evaluate drugs in research. There are a number of methods available for the determination of artemether in biological fluids. These methods include HPLC based UV detection, GS-MS, HPLC-ECD and HPLC-MS/MS. This article reviews different methods for the determination of artemether in the biological fluids. Among the available methods HPLC-MS/MS proves to be the most accurate and reliable one for analysis. This has the advantage of improved sensitivity and selectivity with smaller sample volume.

Frequency of CYP2D6*10 genotypes in Pakistani breast cancer patients taking adjuvant tamoxifen.

OBJECTIVE: To investigate the frequency of cytochrome P2D6*10 in breast cancer patients. METHODS: This retrospective study was conducted at the Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad, and the Combined Military Hospital, Rawalpindi, Pakistan, and comprised medical records of breast cancer patients from January 2000 to September 2013. Pre- and post-menopausal women with diagnosed breast cancer who were advised 20mg/day of tamoxifen as adjuvant therapy were included. The frequency of the cytochrome was determined using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of the 232 participants, 25(10.8%) had stage I disease, 127(54.7%) had stage II and 80(34.5%) had stage III disease. The overall mean age was 46.9±9.9 years. The allele frequency of cytochrome CYP2D6*1 was 431(93%) and that of CYP2D6*10 was 33(7 %). Pakistanis differed significantly from the Asian populations and other ethnic groups in the distribution of the allele cytochrome, but its frequency was comparable to South Indians. CONCLUSIONS: The frequency of CYP2D6*10 allele in Pakistani breast cancer women was comparable to the South Indians, but was significantly lower than other populations.

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.