Clinical efficacy and tolerability of Gabapentinoids with current prescription patterns in patients with Neuropathic pain.

OBJECTIVE: To investigate the current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain and to compare their clinical efficacy and tolerability in terms of pain relief and adverse effects using difference in pain score as a treatment outcome. METHODS: This observational, prospective study was conducted in 320 patients with neuropathic pain from August 2016 to March 2018 at Basic Medical Sciences Institute (BMSI), Karachi in collaboration with Shifa International Hospital and Benazir Bhutto Hospital, Islamabad. Demographic data, treatment-related adverse effects and pain intensity was documented at recruitment and follow up visits at two, four and eight weeks. Discontinuation due to adverse effects and lack of efficacy were also recorded. Data was entered and analyzed using SPSS version 22. RESULTS: Mean age of patients was 52.57±12.47 and the most common ethnicity were Punjabi speaking population (66%). Diabetic neuropathy (51%) was the most common etiology followed by radicular pain (25%). Mean dosages of pregabalin and gabapentin were 114mg and 470mg respectively. Mean pain score was significantly reduced by gabapentinoids (<0.001). Dizziness, drowsiness and somnolence were frequent adverse effects. Common dosages for pregabalin and gabapentin were 75 mg/day and 300 mg/day respectively. CONCLUSION: Current dosing regimens of gabapentinoids in Pakistani patients with neuropathic pain were found to be efficacious at low dosages in comparison to international recommended dosages. Gabapentin and pregabalin were both similar in terms of reducing pain score but onset of pain relief was relatively faster with pregabalin. Dizziness, drowsiness and somnolence were frequently reported with both gabapentinoids; however, visual blurring, ataxia and weight gain were observed only with the use of pregabalin. Adverse effects are frequently observed with gabapentinoids which necessitates reverting back to low dosages or switching to other drugs for pain relief.

Prevalence of vitamin D deficiency and insufficiency among adult asthmatic patients in Karachi.

Vitamin D deficiency has assumed pandemic proportions all over the world. It has been documented as a frequent problem in studies of young adults, elderly person and children in other countries, but there is no reliable data on vitamin D status of adult asthmatic patients in Pakistan. To determine the prevalence of vitamin D deficiency and insufficiency in adult asthmatic patients with moderate to severe asthma using a cross-sectional study design in Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi.311 adult asthmatic patients with moderate to severe asthma were recruited from JPMC, tertiary care hospital in Karachi. Questionnaires were administered together demographics, height, weight, nutritional and physical activity assessment. Blood samples for vitamin D measurement were also taken. Results show high prevalence of vitamin D deficiency and insufficiency (88.10%) in adult patients with moderate to severe persistent asthma. Vitamin D deficiency and insufficiency was more frequently observed in female than in male patients.67.66% of the female patients had serum vitamin D level less than 20 ng/ml as compare to 56.1% of the male patients (p=0.01).

Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin.

Biological screening of Scrophularia nodosa extract and its fractions.

Biological screening of Scrophularia nodosa crude extract and its fractions (hexane, chloroform, ethyl-acetate, n-butanol and aqueous) was carried out on phytotoxicity, cytotoxicity, antibacterial, antifungal and analgesic activities. Crude extract and its fractions produced 50-100% phytotoxicity at 1000µ/mL concentration whereas 25-77% phytotoxicity was observed at 10µ/mL concentration. The fractions exhibited significant antibacterial and antifungal effects. The non-toxic results of this plant were recorded in Brine Shrimps Bioassay method at all concentrations. Similarly no significant insecticidal activity was observed in crude extracts and fractions. Analgesic activity results of S. nodosa in mice were found highly significant in crude extract as compared to fractions. In writhing test crude extract at 500 mg/kg showed 65.6% highest inhibitory response in mice.

Lack of impact of OCTN1 gene polymorphisms on clinical outcomes of gabapentinoids in Pakistani patients with neuropathic pain.

BACKGROUND AND OBJECTIVE: Gabapentinoids are the first-line drugs for neuropathic pain. These drugs are the substrate of organic cation transporter (OCTN1) for renal excretion and absorption across the intestinal epithelium. Gabapentinoids exhibit wide interindividual variability in daily dosage and therapeutic efficacy which makes titration regimens prolonged for optimal efficacy. The present study aimed to investigate the possible influence of the single nucleotide polymorphism (SNP) of OCTN1 on therapeutic efficacy and safety of gabapentinoids in neuropathic pain patients of the Pakistani population. METHODS: Four hundred and twenty-six patients were enrolled in the study. All participants were genotyped for OCTN1 rs1050152 and rs3792876 by PCR-RFLP method and followed up for eight weeks. The therapeutic outcomes of gabapentinoids, reduction in pain score, inadequate or complete lack of response, adverse events (AEs) in responders and discontinuation of treatment on account of AEs were recorded for all patients. RESULTS: There was no significant association of genotypes and alleles of both SNPs on the clinical response of gabapentinoids (P ˃ 0.05). Similarly, significant differences were not found in the reduction of pain scores and AEs among different genotypes in the responders. The present study has reported the association of OCTN1 rs1050152 and rs3792876 polymorphisms with clinical outcomes of gabapentinoids for the first time in the real-world clinical setting. CONCLUSION: Our results suggest a lack of influence of OCTN1 genetic variants in the determination of clinical response to gabapentinoids in patients with neuropathic pain in the Pakistani population. These findings signify the role of renal functions in predicting the interindividual variability to therapeutic responsiveness of gabapentinoids.

Influence of single nucleotide polymorphism of LAT1 on therapeutic response to gabapentinoids in Pakistani patients with neuropathic pain.

Gabapentinoids are substrate of L-type amino acid transporter 1 (LAT1) for distribution across the blood-brain barrier. The present study aimed to evaluate the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and tolerability of gabapentinoids in Pakistani patients with neuropathic pain. Three-hundred and ninety-two patients were recruited, genotyped for SNP rs4240803, and followed up for eight weeks to evaluate the clinical response to gabapentinoids in terms of pain relief, inadequate response, and the emergence of adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the treatment and 17.6% discontinued either due to insufficient response or intolerable adverse events (AEs). GA genotype was more frequent in non-responder group (P Ë‚ 0.001). Maximum pain responders (≥50%) in combination with the lowest incidence of AEs were observed in the GG group, whereas partial responders belonged to GA genotype and with the highest frequency of somnolence (83.6%) and dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs (P Ë‚ 0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered to evaluate the maximum potential of gabapentinoids in the management of neuropathic pain.

Comparison of Bioelectrical Impedance and Navy Seal Formula to Measure Body Composition in Medical Students.

Objectives There are many different ways to measure body composition and bioelectric impedance is one of the most popular methods to measure body ratios. The navy-seal formula is another simple way of measuring body fat ratio which takes into account simple variables such as gender, weight, height, waist, hip and neck circumference. The objective of our study was to compare the results of body fat composition by these two methods. Materials and methods Height and weight were measured in 85 study participants using a wall-mounted stadiometer and digital scale. Body composition measurements were recorded using a simple measuring tape. Participants were then asked to stand on the electrical impedance machine to determine the body fat and muscle mass. Data were analyzed on IBM's statistical package for the social sciences (SPSS) version 23 (IBM, Armonk, NY). Results The Navy-seal formula had slightly higher values for both muscle mass and body fat ratio in both genders and across all body mass index (BMI) categories. Body fat ratio and muscle mass of both genders were similar in underweight, normal, over weight and obese participants. In males, the results on two instruments showed more similarity with the increase in BMI, whereas, in females, the results of the two methods were more similar in the normal weight category. Conclusion Navy-seal formula and bioelectrical impedance are both simple and reliable instruments to measure body composition in adults. The navy-seal formula can be used to screen individuals with high-fat body fat ratio whereas bioelectric impedance can be used to measure the body composition for personal monitoring.

Role of Pitavastatin in Prevention of Osteopenic Changes in Ovariectomized Rats.

OBJECTIVE: To determine the effect of pitavastatin, a third generation statin, on development of osteopenia in ovariectomized rats. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Pharmacology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi, from January to July 2013. METHODOLOGY: Forty female Sprague Dawley rats were divided into ovariectomized (OVX), Sham OVX and OVX given pitavastatin 0.4 mg/kg/day, 0.8 mg/kg/day, for 8 weeks. Bone density measurements using CT scan and Archimedes’ principle were made on femora and tibiae. Blood samples were analyzed for acid phosphatase (ACP) and alkaline phosphatase (ALP) levels. RESULTS: Ovariectomy-induced osteopenic changes were indicated by significant decrease in bone densities and Hounsfield (HU) index of distal femoral and proximal tibial metaphyses and elevation of ACP and ALP levels. 0.4 mg/kg pitavastatin did not significantly alter the evaluated parameters. 0.8 mg/kg produced a restoration of HU of lower femur and femoral density comparable to Sham. HU of upper tibia and tibial density following 0.8 mg/kg was significantly higher than OVX but was not approximate to Sham. ALP and ACP with 0.8 mg/kg were comparable to Sham. CONCLUSION: Supra-therapeutic dose of pitavastatin was effective in preventing estrogen deficiency-induced decrease in bone density of ovariectomized rates, over an 8-week period.