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|Year : 2015 | Volume
| Issue : 7 | Page : 10-13
UK Sheth Prize
|Date of Web Publication||11-Dec-2015|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. UK Sheth Prize. Indian J Pharmacol 2015;47, Suppl S1:10-3
Hepatic and Hematological Adverse Effects of Long Term Low Dose Methotrexate Therapy in Rheumatoid Arthritis: An Observational Study
Lily Dubey 1 , Suparna Chatterjee 1 , Alakendu Ghosh 2
1 Department of Pharmacology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India, 2 Department of Rheumatology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
Objectives: Methotrexate is the most commonly used cost effective disease-modifying anti-rheumatoid drug. Their doses limiting adverse effects are hepatic and hematopoietic. However, data pertaining to its safety profile in Indian population is limited. This cross-sectional observational study evaluated the prevalence of hepatic and haematological adverse effects and potential risk factors associated with long term low dose methotrexate therapy. Materials and Methods: RA patients taking ≤15 mg/week methotrexate for ≥2 years were enrolled from the Rheumatology OPD. Demographic, disease, drug treatment profiles, and haematological and hepatic enzyme levels were noted. Results: 204 patients were enrolled with mean age of 44.1 ± 9.8 years, median disease duration (IQR 3-7) and methotrexate intake of 4 years (IQR 2-6). Prevalence of raised ALT level (ALT ≥2 upper limit of normal) was 13.73% (95% CI 9.67-19.13). Fifteen patients (7.3%) had ALT levels ≥2 fold but <3 fold rise and 13 (6.4%) had ≥3 fold rise of ALT levels and one case of biopsy proven hepatic fibrosis. 5.4% (95% CI 3.04-9.39) had severe anaemia (<8 g/dl), while 4.4% (95% CI 2.34-8.17) had leukopenia. Gender, disease duration, cumulative methotrexate dose or concomitant DMARD intake were not significantly different amongst those with ALT levels ≥2 ULN versus those with <2 times ULN. Conclusion: Long term low dose methotrexate is safe in RA patients in Indian population. The patterns of adverse effects were similar to those documented in earlier studies. However our study results suggest that disease duration, cumulative methotrexate dose, concomitant DMARD intake are not risk factors associated with hepatic or haematological adverse effects.
Pharmacokinetic and Pharmacogenomic Correlation of Blood Levels of Rifampicin in Patients with Tuberculosis
Daniel S 1 , Roy V 1 , Lomash A 2 , Kapoor S 2 , Khanna A 3 , Arya A 1
1 Department of Pharmacology, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India, 2 Department of Pediatrics, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India, 3 Chest Clinic, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India
Objectives: To evaluate the association of blood concentrations of rifampicin (RMP) achieved in patients with tuberculosis (TB) with genetic polymorphism in SLCO1B1 (c.463C>A, c.388A>G) at doses administered according to India's Revised National Tuberculosis Control Programme (RNTCP) 2014. Materials and Methods: Prospective, open label, non-randomized single-dose study in 72 adult patients aged 18-65 years. RMP blood levels were estimated at 0, 1, 2, 3, 4, 6, 8 & 12 hours. Pharmacokinetic parameters (Cmax, Tmax, AUC, t 1/2 , V d , Cl, K el ) were calculated and variants of SLCO1B1 (c.463C>A, c.388A>G) were determined. Results: The peak RMP concentration (Cmax) attained was 9.34 μg/ml (range 7.12-12.18 μg/ml) at time to Cmax of 2.15 h (range 2-3 h). The area under the curve AUC (0-12) was 42.2 μg*h/ml (range 28.71-53.69 μg*h/ml). In 12 out of 72 patients the peak RMP concentration was <8 μg/ml, a level considered too low for therapeutic efficacy. All patients expressed wild type (CC) of allele for SLCO1B1 c.463C>A. Wild and alternative type (GA & GG) of allele for SLCO1B1 c.388A>G were in majority of the patients having peak RMP concentration <8 μg/ml. Conclusion: RMP peak levels observed were similar to observed in adults however RMP peak levels achieved were higher, elimination half-life longer and clearance slower than those observed in children. No correlation between RMP levels & genotype of SLCO1B1 c.463C>A, and presence of variants of SLCO1B1 c.388A>G with low RMP levels suggests that more studies need to be done with a larger sample size to see the association of genetic polymorphism with levels of RMP.
A Comparison of Quality of Prescriptions at Primary, Secondary and Tertiary Health Care Facilities Using Prescription Quality Index Tool
Suthar JV 1 , Patel VJ 2
1 Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa, Gujarat, India, 2 Department of Pharmacology, NHL Municipal Medical College, Ahmedabad, Gujarat, India
Background and Objectives: Several tools have been introduced to evaluate the quality of prescribing. The study aim was to determine the quality of prescribing in hypertension and bronchial asthma in primary, secondary and tertiary health care setting using the new Prescription Quality Index (PQI) tool and to assess the reliability of this tool. Materials and Methods: A prospective cross-sectional study was carried out at selected PHCs, SHCs and THC facility for chronic conditions in order to assess the quality of prescribing using PQI. Patients with hypertension and bronchial asthma, attending out-patient departments of each health care facility for at least 3 months were included. Complete medical history and prescriptions were noted. Total and criteria wise PQI scores were derived for each prescription and prescriptions were categorized as poor, medium and high quality. Results: A total 356 patients was included. Mean age was 57.7 ± 14.7 years (range 4-87 years) with 36% patients above 65 years of age. Mean total PQI score was 28.9 ± 8.1. Of 356 prescriptions, 138 (38.8%) prescriptions were of high quality with PQI score ≥34. Prescribing quality in terms of PQI score showed significant difference between PHC, SHC and THC (P < 0.0001). The prescribing quality between PHCs and SHCs did not differ significantly (P > 0.05). The value of Cronbach's α for the entire 22 criteria of PQI was between 0.68 to 0.89. Conclusion: As evaluated by PQI tool, the quality of prescribing at THC was better as compared to SHCs & PHCs. PQI was found to be a reliable tool for assessment of prescribing quality in chronic diseases.
An Analysis of Serious Adverse Drug Reactions at Tertiary Care Teaching Hospital
Kinjal Prajapati 1 , Mira Desai 1 , Samidh Shah 1 , Jigar Panchal 1 , Jigar Kapadia 1 , Dikshit RK 2
1 Department of Pharmacology, B.J. Medical College, Ahmedabad, Gujarat, India, 2 Department of Pharmacology, GCS Medical College, Ahmedabad, Gujarat, India
Objectives: To analyze various aspects of serious adverse drug reactions (ADRs) such as clinical presentation, causality, severity and preventability occurring in hospital setting. Materials and Methods: All serious ADRs reported from January, 2010 to May, 2015 at ADR monitoring centre, Department of Pharmacology, B.J. Medical college and Civil Hospital, Ahmedabad were selected as per WHO-UMC criteria. A retrospective analysis was carried out for clinical presentation, causality (as per WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and seigel scale) and preventability (Schumock and Thornton criteria). Results: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for majority of serious ADRs was intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%) and two were fatal. Majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. A substantial number of the serious ADRs were mild (275, 73.3%) and not preventable (360, 96%). Conclusion: Antitubercular, antiretroviral and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.
Effect of Vitamin D Supplementation in Patients of Moderate Asthma Undergoing Treatment with Inhaled Corticosteroids
Rajendra Sharma, Juhi Kalra, Dhasmana DC, Sanjeev Kumar
Department of Pharmacology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
Objectives: Vitamin D is an essential nutrient with significant immunomodulatory effects. There is potential for a protective role of vitamin D against etiopathogenesis of asthma and morbidity. This study evaluated the effect of vitamin D supplementation in patients with moderate asthma. To evaluate the effect of vitamin D supplementation on lung function improvement in patients of moderate asthma undergoing treatment with inhaled corticosteroids. Materials and Methods: An interventional prospective study. A total of 60 patients of moderate asthma were enrolled in the study and randomly divided into two groups of 30 patients each. Group A: placed on steroid based treatment regimen (formoterol 6 μg + budesonide 200 μg) + vitamin D supplementation (60,000 IU/week for 8 consecutive weeks). Group B: placed on steroid based treatment regimen (formoterol 6 μg + budesonide 200 μg) only, as control. The enrolled patients were followed up for 12 weeks and assessed for various parameters of disease severity, asthma control and improvement in lung function by using asthma control test (ACT) questionnaire and pulmonary function tests (spirometry). Collected data was analyzed using available statistical software (SPSS Ver. 20.0). Results: Statistically significant changes (P < 0.001) were seen in pre to post values of FEV1 (2.28 ± 0.41 to 2.64 ± 0.51), FVC (3.37 ± 0.74 to 3.60 ± 0.76) and FEV1/FVC ratio (68.44 ± 5.03 to 73.48 ± 3.52) in Group A as well as in Group B i.e. FEV1 (2.28 ± 0.48 to 2.64 ± 0.52), FVC (3.35 ± 0.67 to 3.58 ± 0.75) and FEV1/FVC ratio (67.87 ± 2.48 to 74.16 ± 4.19). However there were no significant differences observed in pre and post values of FEV1, FVC and FEV1/FVC ratio in between the two groups. Conclusion: Vitamin D supplementation failed to show additional benefits in lung function improvement in adults with moderate asthma undergoing treatment with inhaled corticosteroids in the present study.
Critical Analysis of Cardiovascular and Central Nervous System Fixed Dose Combinations Available in Indian Market
Krunal Prajapati, Samidh Shah, Mira Desai
Department of Pharmacology, B.J. Medical College, Ahmedabad, Gujarat, India
Objectives: To analyze the rationality of cardiovascular (CVS) and central nervous system (CNS) fixed dose combinations (FDCs) available in Indian market. Materials and Methods: CVS and CNS FDCs, enlisted in Indian Drug Review (IDR) 2014, were analyzed by a pretested validated 8 point criteria tool. Each FDC was assessed for number of active pharmacological ingredients (API), approval by regulatory authority, listing in WHO Essential Medicine List (EML) or National List of Essential Medicine, while efficacy, safety, pharmacokinetic and pharmacodynamic interactions and advantages of each FDC were analyzed by evidence based literature search. Each criterion was scored one for positive and minus one for negative or unfavorable observation. The total score for the tool was 12 and score ≥7 was considered rational. Results: Out of 152 FDCs, 107 were CVS and 45 belonged to CNS group. The mean rationality score was 6.59 ± 2.68 (95% CI, 3.91-9.27). Majority of FDCs were irrational (97) while 55 were rational and only one was listed in WHO EML 2013 (carbidopa + levodopa). Out of 107 CVS FDCs, 46 (43%) were rational while 61 (57%) were irrational. Out of 45 FDCs in CNS, 9 (20%) were rational while 36 (80%) were irrational. 35 irrational FDC were approved by DCGI while there were 13 rational FDCs, however, not approved by DCGI. Among the rational FDCs, 32 FDCs had advantages of less adverse drug reactions (ADRs) when compared to individual API. While favorable pharmacokinetic interactions were observed in 3 FDCs. Conclusion: A substantial number of CVS and CNS FDCs in Indian market are irrational. This calls for a need for strict regulatory approval for FDCs.
Study of Prescribing Pattern and Cost of Medical Therapy in Patients of Metabolic Syndrome in North Indian Population
Prashant, Anita Gupta, Vijay Sehgal K, Raghuvansh Kumar
Department of Pharmacology, Government Medical College, Patiala, Punjab, India
Objectives: The aims and objective of the present study are as follows: To study the prescription patterns in diagnosed patients of metabolic syndrome. To study the cost of medical therapy in diagnosed patients of metabolic syndrome. Materials and Methods: This was an observational, cross sectional study in which one hundred prescriptions were be collected randomly from diagnosed metabolic syndrome patients on medical therapy attending the Medicine OPD of Government Medical College and Rajindra Hospital, Patiala. The patients fulfilling the inclusion criteria and after verifying the exclusion criteria were included in this study. The required information was noted. All the prescriptions were analyzed for the pattern of the medication prescribed. The cost of treatment of metabolic syndrome was calculated for each prescription by adding daily cost of all the medications being used by the patients. All the observations thus made were statistically analyzed using appropriate tests. Results: Prescription patterns: The prescription patterns reflected the symptamatology of the syndrome. The prescription of the patients included mainly anti-diabetic drugs, anti-hypertensive drugs, hypolipidemic drugs and multivitamins. Out of 50 patients, 49 patients were on anti-diabetic drugs, 40 patients were on anti-hypertensive drugs and 28 patients were on hypo-lipidemic drugs. The most commonly prescribed anti-diabetic drug was biguanides, while the most commonly prescribed anti-hypertensive drug was angiotensin receptor blockers and statins were the most commonly prescribed hypolipidemic drug. The daily cost of therapy was Rs. 44.56. Extrapolating the results gives us the monthly cost of therapy of Rs. 1336.90 and an annual cost of therapy of 16264.40. There was significant difference in the cost of therapy among males and females as well as among various age groups. Conclusion: Our findings suggest that patients with metabolic syndrome have clustered components, like obesity, hypertension, and dyslipidemia which bears a close reflection on the prescribing patterns. Similarly the cost of medical therapy of metabolic syndrome was quite high if compared with the per capita income of India.
A Randomized Double-blind Controlled Study Comparing the Efficacy and Safety of Controlled Release Morphine with Immediate Release Morphine for Cancer Pain in Palliative Care Patients
Indumathi Prapath 1 , Gunaseelan Karunanidhi 2 , Gitanjali Batmanabane 1
1 Department of Pharmacology, JIPMER, Puducherry, India, 2 Department of Radiotherapy, Regional Cancer Centre, JIPMER, Puducherry, India
Objectives: This study compared the efficacy and safety of controlled release (CR) morphine with immediate release (IR) morphine for treating pain in advanced stage cancer patients. Materials and Methods: This was a randomized double-blind placebo-controlled crossover study in cancer patients requiring morphine more than 60 mg/day. Pain intensity using BPI questionnaire and visual analog scale, plasma concentration of morphine, frequency of adverse effects and number of rescue doses of morphine required were assessed after three weeks of treatment and the median values were compared between the two treatment groups. Wilcoxon matched-pairs signed rank test and chi-square test were used for analyzing the results. Results: Seventy patients were included in the study. Pain intensity assessed at terminal period of analgesic action, frequency of common adverse effects except sedation, number of rescue doses did not show statistically significant difference between the two groups. At pre dosing time, pain intensity of IR morphine patients was significantly lower than CR morphine patients (p = 0.018). Plasma concentration of morphine (25.9 ± 15.1 ng/ml) during the terminal period of analgesic action and sedation were higher in CR morphine patients. Most of the study patients preferred IR morphine (75.7%) over CR morphine (24.3%) for the continuation of pain therapy. The cost of CR morphine was three times more than IR morphine. Conclusion: IR morphine may be preferred over CR morphine for cancer pain treatment as it offers almost similar analgesic effect and safety profile at a lower cost with higher patient preference than CR morphine.
Prescription Patterns in Type 2 Diabetes Mellitus Patients Presenting to a Tertiary Care Centre in North Karnataka
Nara Manisha, Kulkarni GP, Gumma KM
Department of Pharmacology, Bidar Institute of Medical Sciences, Bidar, Karnataka, India
Objectives: The aim of present study is to, (a) study the prescribing patterns of antidiabetic drugs for patients diagnosed with type 2 diabetes mellitus, (b) to compare with the standard guidelines for treatment of diabetes mellitus as per International Diabetes Federation and American Diabetes Association. Materials and Methods: A retrospective study was undertaken, over duration of 6 months at the government teaching hospital, Bidar Institute of Medical Sciences, Bidar. Patients of either sex admitted to medical wards with a diagnosis of type 2 diabetes mellitus were included. Data collection was done by scrutinizing the inpatient case sheets and treatment charts. Individual data was collected on preformed Performa. Results: A total of 1020 patients were identified. Mean age of the patients was 56 years and 58.2% of the study populations were males. 45.6% of the study population was treated with monotherapy and the rest with more than one drug. 32.4% of the population received fixed drug combination. 25.9% of the population was receiving insulin. Metformin was the most common drug used. Glimepride was the most common sulfonylurea used. Insulin analogues, incretins and newer agents were sparingly used. Conclusion: Monotherapy with oral hypoglycemic agents was the predominant prescription and newer agents were sparingly used.
Comparison of Efficay and Safety of Cilnidipine and Losartan in Patients of Hypertension with or Without Diabetes from Gwalior, India
Bhalerao Mayuri 1,2 , Kothari Saroj 1,2 , Rastogi Puneet 1,2
1 Department of Pharmacology, Gajra Raja Medical College, Gwalior, Madhya Pradesh, India, 2 Department of Cardiology, Gajra Raja Medical College, Gwalior, Madhya Pradesh, India
Objectives: Comparison between cilnidipine & losartan with respect to changes in blood pressure and heart rate in hypertensive patients with or without type 2 diabetes mellitus. Materials and Methods: We conducted alongitudinal, prospective, open labelled, comparative clinical study of hypertensive patients with or without type 2 DM. Total 161 hypertensive patients of either sex presenting to cardiology clinic were enrolled and were randomly allocated into 4 groups. Group I (n = 43) received 10-20 mg of cilnidipine orally once daily. Group II (n = 41) received losartan 50-100 mg orally once daily. Group III (n = 38) patients with type 2 DM received cilnidipine 10 mg orally once daily. Group IV (n = 39) patients with type 2 DM received losartan 50 mg orally once daily. The dosages of the drugs were adjusted if the magnitude of reduction was insufficient. The blood pressure (BP) and heart rate (HR) were monitored during followup at 4, 8 and 12 weeks. Results: Levels of systolic (SBP), diastolic blood pressure (DBP) and HR significantly decreased with both cilnidipine and losartan, within 4 weeks of therapy, and these levels continued to decrease until the end of the study. However, on comparison, magnitude of HR reduction was greater with cilnidipine treatment groups as compared to losartan groups with statistically significant difference between groups (HR group I 70.6 ± 9.15 versus 79 ± 8.3, p = 0.000032) and (HR group III 79.34 ± 7.44 versus group IV 82.67 ± 7.15, p = 0.048). Of total 161 patients, only 1 patient experienced Hot flushes from group I receiving cilnidipine. Other than this, no adverse drug reactions were reported and overall both the drugs were well tolerated. Conclusion: The present study demonstrated that therapy with cilnidipine can be used safely and effectively in hypertensive patients with or without diabetes. Cilnidipine was equally efficacious in lowering BP, while it more effectively reduced HR as compared to losartan. Cilnidipine can, therefore, be recommended as an alternative especially when there is associated tachycardia.