Research Letter

syndrome. Similar observation was reported earlier.[7] There was a significant rise in blood glucose level in rats treated with quetiapine, 30 mg/kg (group III). This rise in blood glucose and triglyceride level in this group III implies that quetiapine aggravate the metabolic syndrome induced by CAR. The nonsignificant per se effect of rosuvastatin (10 and 20 mg/kg) and CDP‑choline (100 mg/kg) on glucose level of CAR‑induced rats reveals that rosuvastatin and CDP‑choline did not aggravate metabolic syndrome. However, the reduction of quetiapine induced rise in glucose and TG levels by rosuvastatin and CDP‑choline reveals that these drugs could attenuate the metabolic syndrome caused by quetiapine. The nonsignificant changes in the liver glycogen level of CAR‑induced rats and quetiapine‑treated rats indicate that liver plays a minor role in the metabolic syndrome caused by CAR or quetiapine. The reduction of glycogen levels caused by rosuvastatin reveals that statins have mild adverse affect on liver glycogen storage capacity. However, the nonsignificant effect of CDP‑choline on liver glycogen reveals that CDP‑choline did not produce adverse effects on liver function. The nonsignificant effects of rosuvastatin and CDP‑choline on liver glycogen levels of quetiapine‑treated CAR‑induced rats further confirm that these two drugs attenuate. Study concluded that rosuvastatin and CDP‑choline could decrease the metabolic syndrome caused by quetiapine and CAR. It was observed that after induction of CAR in rats for 7 days, the fasting glucose level was considerably increased as compared to fasting blood glucose level of normal rats, suggesting that schizophrenia itself can lead to glucose imbalance.

Ahmad Shafique, K. K. Pillai, Abdi Sayed Aliul Hasan, A. K. Najmi Department of Pharmacolgy, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India Address for correspondence: Ahmad Shafique, Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, India. E‑mail: [email protected]




4. 5. 6.

Yumru M, Savas HA, Kurt E, Kaya MC, Selek S, Savas E, et al. Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord 2007;98:247‑52. Basu R, Brar JS, Chengappa KN, John V, Parepally H, Gershon S, et al. The prevelance of the metabolic syndrome in patients with shizoaffective disorder bipolar subtype. Bipolar Disord 2004;6:314‑8. Fagiolini A, Frank E, Houck PR, Mallinger AG, Swartz HA, Buysse DJ, et al. Prevalence of obesity and weight changes during treatment in patients with bipolar disorder. J Clin Psychiatry 2002;160:112‑7. Haupt DW, Newcomer JW. Abnormalities in glucose regulation associated with mental illness and treatment. J Psychosom Res 2002;53:925‑33. Newcomer JW. Second generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review. CNS Drugs 2000;19:1‑93. Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 2010;1:87‑93.


Dwyer DS, Donohoe D. Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. Pharmacol Biochem Behav 2003;75:255‑60. Access this article online Quick Response Code:


DOI: 10.4103/0976-500X.119715

Cardiovascular medications among the critically ill patients of a tertiary care hospital: A drug utilization study Sir Cardiovascular disorders are one of the leading causes of mortality and morbidity. The patients admitted to the medical intensive care unit (MICU) represent a diverse patient population with variable demographic characteristics and admission criteria. A substantial proportion of patients admitted to the MICU with non‑cardiac illnesses have associated cardiac co‑morbidities. The critically ill patients represent a high risk population in whom judicious and appropriate pharmacotherapy can be life‑saving while irrational use of medications can be life‑threatening. Prescription audits help to evaluate and recommend modifications in current prescribing practices of physicians to ensure rational and quality medical care.[1] Developing countries have limited funds available for health care and drugs. Drug utilization studies review the concordance of current drug prescription pattern with the treatment protocol.[1] This study aimed to evaluate the utilization pattern of cardiovascular drugs in a consecutive series of patients admitted to MICU. A prospective observational study was carried out over a period of one year at St. John’s Medical College Hospital, Bangalore, India. The study was approved by the institutional ethics committee before the conduct of the study. Consecutive

Journal of Pharmacology and Pharmacotherapeutics | October-December 2013 | Vol 4 | Issue 4


Research Letter

patients admitted to the MICU during the study period were included as the study population. Patients transferred to other units within a day of admission to the MICU were excluded. We reviewed all the patient prescriptions, and the details were recorded during that particular hospital stay on to a case record form. Descriptive statistical analysis was carried out using SPSS version 18. Individual cardiovascular drugs were classified based on WHO‑ATC classification. Totally 728 (81%) consecutive patients fulfilled the inclusion criteria. Male patients constituted 65% of the total. The mean and standard deviation (SD) for age was 49.2 ± 15.8 years. The common cardiovascular conditions in MICU patients included coronary artery diseases such as ischemic heart disease, hypertension, dyslipidemia, myocardial infarction and congestive heart failure. This finding implies that the majority of patients admitted to the MICU had chronic cardiovascular diseases. Of the various cardiovascular drug classes, 40% and 20% of the drugs belonged to WHO essential drug list and complementary drug list, respectively. Sixty‑eight percent of the drugs were prescribed by their trade names. Out of 1173 cardiovascular drugs prescribed, the top four drug classes were inotropes (478 patients), anti‑hypertensives (337 patients), hypolipidemic agents (119 patients) and diuretics (114 patients). Among the drugs prescribed for hypertension, calcium channel blockers (amlodipine) were the most utilized drug class. Table 1 shows the utilization patterns of cardiovascular drugs in MICU. Low molecular weight heparins (LMWH) were the frequently prescribed anticoagulants, Dalteparin (B01AB04) (119 patients Table 1: Utilization pattern of cardiovascular drugs in the MICU (except anti‑hypertensives) Drug group



Noradrenaline Dopamine Dobutamine Adrenaline Hypolipidemic Atorvastatin Simvastatin Diuretics Furosemide Spironolactone Anti‑anginals Isosorbide mononitrate Diltiazem Nitroglycerine Nicorandil Anti‑arrhythmics Amiodarone Verapamil Cardiac glycosides Digoxin Peripheral vasodilators Pentoxifylline MICU=Medical intensive care unit


ATC code C01CA03 C01CA04 C01CA07 C01CA24 C10AA05 C01AA01 C03CA01 C03DA01 C01DA08

No. of prescriptions (n=728) 220 (30.2) 165 (22.7) 70 (9.6) 23 (3.2) 109 (15) 8 (1.1) 91 (12.5) 13 (1.8) 42 (5.8)

C08DB01 C01DA02 C01DX16 C01BD01 C08DA01 C01AA05 C04AD03

25 (3.4) 22 (3) 8 (1.1) 21 (2.9) 2 (0.3) 16 (2.2) 8 (1.1)

16.3%) being the commonest LMWH. Among the anti‑platelet drugs, 153 (21%) patients were on low dose aspirin (B01AC06) and 95 (13%) patients on clopidogrel (B01AC04). As regard the clinical outcome, 575 (78.9%) patients had their clinical condition improved and were transferred from MICU, while 94 patients (12.9%) died. The clinical outcome of 60 patients was not known as they were either discharged against medical advice or on the patients’ requests. Rational prescription is essential for better patient care. The first step in any intervention program to improve drug utilization is to assess the extent of the existing problem in prescribing. Male preponderance and mean age group of the patients were similar to the findings by Biswal et al.[2] The relatively high proportion of trade name prescriptions (68%). Many clinicians prefer prescribing by trade name due to the existence of numerous imitation drugs in the market. The prescriptions of cardiovascular medications were in line with the cardiovascular diagnosis in the patients. About 40% of the cardiovascular drugs belonged to the WHO essential drug list. This observation was expected considering the severity of illnesses of the patients admitted to the MICU. The WHO essential medicines list is primarily intended to be aligned with standard treatment guidelines for the common medical conditions in the community and does not include those illnesses observed in the critically ill patients. The majority of the cardiovascular drugs were prescribed to patients for their co‑existing cardiovascular co‑morbidities. Cardiovascular drug utilization was observed for both prophylaxis (anticoagulants, anti‑platelet agents, hypolipidemics) as well as for therapeutic cardiovascular indications. Cardiovascular diseases are a combination of risk factors resulting in clinical events that increase morbidity and mortality. Current guidelines in preventive cardiology focus primarily on the management of major cardiovascular risk factors through dietary and lifestyle modifications, and prophylactic use of various drugs.[3] Inotropes were the most widely used cardiovascular drug category. Noradrenaline (30.2%) followed by dopamine (22.7%) were the most frequently utilized inotropes as the most common primary diagnosis was sepsis (septic shock). This finding was in concordance with the reports of Biswal et al.[2] and Sakr et al.[4] Noradrenaline is favored in shock secondary to sepsis as it is believed to have more potent vasoconstrictor effects in sepsis‑mediated vasodilation and also improves urine output and creatinine clearance in patients with septic shock. [4] This could explain the higher utilization of noradrenaline observed in the present study since sepsis was the most common primary clinical

Journal of Pharmacology and Pharmacotherapeutics | October-December 2013 | Vol 4 | Issue 4

Research Letter

diagnosis. Evidence is still lacking as regard the use of inotropes and vasopressors in the critically ill. Large prospective randomized trials, such as the Sepsis Occurrence in Acutely Ill Patients (SOAP) group, are being carried out with vasopressors that would answer several relevant clinical questions. Drugs for hypertension were the second most frequently used cardiovascular drug category as hypertension (30.4%) was the common co‑morbidity in the study. Atorvastatin 109 (15%) was the most commonly used hypolipidemic agent. Statins are known for their primary and secondary cardiovascular prevention. In addition, recent studies have reported the pleiotropic effects of statin therapy in prevention and treatment of sepsis in the ICU setting.[5] Furosemide was the major diuretic prescribed among the critically ill with acute renal failure (ARF) and congestive heart failure. Diuretics represent one of the most commonly used agents in the ICU to maintain renal function and decrease the requirements for renal support. A meta‑analysis by Ho & Sheridan in 2006 concluded that the diuretics do not provide any clinical benefit in patients with ARF, but studies on diuretics‑associated mortality and morbidity among critically ill are still lacking.[6] Most patients in the MICU have venous thromboembolism (VTE), which is a major risk factor that warrants the use of thromboprophylaxis to prevent VTE and also to decrease the complications of thromboembolic disease. LMWHs were the anticoagulant of choice in our study in concordance with Geerts et al. [7] This observation was dissimilar to the findings of Biswal et al.,[2] where equal proportions of patients received both LMWH as well as unfractioned heparin. Both LMWH and unfractioned heparin are equally efficacious in preventing DVT, but LMWH was preferred in the present study due to the lower incidence of ADRs such as thrombocytopenia and also laboratory monitoring is not essential. The use of anti‑arrhythmic agents was marginal (3%), probably due to reversion of arrhythmias and cardiac arrest carried out primarily using external defibrillators. Infrequent utilization of thrombolytic agents was observed as those patients requiring thrombolytic therapy would be usually shifted to the CCU for further management and thus not available for inclusion in the analysis in the present study.

CONCLUSION A wide spectrum of cardiovascular drugs was used from various drug classes. Cardiovascular drug utilization was observed for prophylaxis as well as for therapeutic indications. Continuous prescription audit in the MICU would give insights into the current practices and feedback for rationalizing prescribing practices. Longitudinal surveillance of ICU drug use can be undertaken with the aim of creating a drug utilization database.

Lisha Jenny John, Padmini Devi1, Shoba Guido1 Departments of Pharmacology, Gulf Medical University, Ajman, UAE, 1 St John’s Medical College, Bangalore, Karnataka, India Address for correspondence: Lisha Jenny John, Department of Pharmacology, Gulf Medical University, Ajman, UAE. E‑mail: [email protected]


4. 5. 6. 7.

Srishyla MV, Krishnamurthy M, Nagarani MA. Prescription audit in an Indian hospital setting using the DDD (Defined Daily Dose) concept. Indian J Pharmacol 1994;26:23‑8. Biswal S, Mishra P, Malhotra S, Puri GD, Pandhi P. Drug utilization pattern in the intensive care unit of a tertiary care hospital. J Clin Pharmacol 2006;46:945‑51. De Backer G, Ambrosioni E, Borch‑Johnsen K, Brotons C, Cifkova R, Dallongeville J, et al. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2003;24:1601‑10. Sakr Y, Reinhart K, Vincent JL, Sprung CL, Moreno R, Ranieri VM, et al. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med 2006;34:589‑97. Merx MW, Weber C. Statins in the intensive care unit. Curr Opin Crit Care 2006;12:309‑14. Ho KM, Sheridan DJ. Meta‑analysis of frusemide to prevent or treat acute renal failure. BMJ 2006;333:420. Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, et al. A comparison of low‑dose heparin with low molecular weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996;335:701‑7. Access this article online Quick Response Code:

Journal of Pharmacology and Pharmacotherapeutics | October-December 2013 | Vol 4 | Issue 4


DOI: 10.4103/0976-500X.119717


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Cardiovascular medications among the critically ill patients of a tertiary care hospital: A drug utilization study.

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