Corticosteroid Utilization Pattern: A Prospective study at a Tertiary Care Teaching Hospital

Shazma Imam¹, Priti Sharma¹, Dinesh Kumar Mehta¹*, Sandeep Joshi², Rina Das¹

¹MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana,

Ambala- Haryana (India) - 133207

²MM Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala- Haryana (India)-133207

*Corresponding Author E-mail: dkmehta17@rediffmail.com

ABSTRACT:

Objectives: This study aimed to explore the prescribing pattern of steroids among patients from different departments and study the most commonly prescribed corticosteroid medications and the assessment of patient knowledge about the use of corticosteroids. Methods: We conducted a prospective observational study on 120 patients receiving corticosteroids in the department of General medicine, Respiratory and Orthopedic in a tertiary care teaching hospital for the period of 6 months. Inpatients between 18-60 years receiving corticosteroid therapy were included in the study, exclusion of those patients who were under critical condition, lactating and nursing mothers and those not willing to sign on inform consent form. Key findings: The study involved 120 patients to evaluate the appropriate use of corticosteroids. The analysis of prescription was done and 24% of the prescriptions were found with drug interactions, the majority of drug interactions were minor (72%), followed by moderate (26%) and no severe interaction was found, and 76% were without interactions. Total 29(24.1%) side effects were found in the study due to corticosteroid use, hypertension was detected in 8 (28%), hyperglycemia in 7 (24%), sleep disturbance in 5 (17%), weight gain in 5 (17%) and gastrointestinal upset in 4 (14%). The use of inhaler was improved in patients from 55% to 83%. Conclusions: The study was found to be rational as the majority of interactions were minor, followed by moderate and no severe interaction was found. Greater awareness for use of corticosteroids is essential; therefore, strategies to improve drug safety, and better patients outcome. Prevention of side effects and rational prescribing can be better achieved by clinical pharmacist’s intervention in patient care

KEYWORDS: Corticosteroids; Disease; Haryana; Rational; Side effects; Steroids.

INTRODUCTION:

Steroids, since their identification in 1935 have wide range of applications in various diseases.^[1]The term steroid is relevant to a wide range of molecules showing varying physiological effects.^[2]Corticosteroids (CS) belongs to the class of chemicals are naturally produced and laboratory-synthesized hormones.^[3]Since their discovery in the 1940s, Corticosteroids play a vital role in the treatment of many diseases including Chronic Obstructive Pulmonary Disease, Asthma, and Rheumatoid Arthritis.

Chronic Obstructive Pulmonary Disease (COPD) is a multidimensional disease with a variety of intermediate and clinical phenotypes.It is estimated that COPD will become the third most common cause of death worldwide by 2030.^[4]COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a common treatable and preventable disease characterized by constant airflow limitation that is usually progressive and coupled with an enhanced chronic inflammatory response to noxious particles or gases in the airway and the lung. Chronic bronchitis and emphysema are associated with COPD.^[5]The pulmonary injury involves three stages i.e, initiation (due to exposure to cigarette smoking, pollutants, and infectious agents), progression and consolidation.^[4]Symptoms including cough with or without sputum, chest pain, breathlessness, decreased the quality of life (QOL) and loss of lung function become worst with acute exacerbations of COPD.During exacerbation of COPD airway inflammation is significantly increased, the number of lymphocytes, eosinophils and neutrophils are elevated in airways and sputum.^[6]Exacerbations play an important role in etiology as it accounts for morbidity, mortality, and associated costs with COPD.^[7]Studies have shown that the use of corticosteroids improves short term lung function and decreases the rate of treatment failure as well as the length of hospital stay. But their side effects made them unsuitable to treat long term stable COPD. The inhaled form of corticosteroids proved to be highly effective in the treatment of COPD and asthma.^[7]

The prevalence of asthma has been increased rapidly over the last few decades and it is estimated that there are 334 million sufferers of asthma worldwide.^[8]

Asthma is a respiratory condition which consists of increased airway hyper-responsiveness and increased episodes of obstruction and inflammation of lungs due to hyperactive inflammatory replications towards agents such as dust, chemicals and allergic pathogens.^[9]The disease is characterized by recurrent episodes of cough, wheezing, and breathlessness.^[10]The central feature of bronchial asthma is airway inflammation.The main changes related to the airway circulation include the proliferation of blood vessels (angiogenesis),^[11]increased blood flow,^[12]increased micro vascular permeability,^[13]and edema formation in the airway wall. ^[14]There is no cure for asthma, but the symptoms can be controlled by advanced and conventional therapy.^[15] The current asthma treatment aims at decreasing day-to-day asthma symptoms and reducing future risks which includes severe exacerbations, hospitalizations, and death which can be decreased by inhaled corticosteroids (ICS). ICS are the strength for the standard of care in long-term treatment of asthma.^[16] They are the most commonly used treatment for asthma which can suppress the characteristic inflammation in airways.^[17]

Rheumatoid Arthritis is an autoimmune disease which affects nearly 1% population all over the world.^[18] It is characterized by inflammation of synovial and destruction of a joint which can cause severe disability if left untreated.^[19]It mainly affects the small joints of hands and feet. It is a chronic inflammatory disease which causes pain, swelling and stiffness. The disease has no cure yet. Symptomatic treatment can be given to the patients suffering from RA which can increase the quality of life. Treatment includes disease modifying anti-rheumatic drugs (DMARTs), non-steroidal anti-inflammatory drugs (NSAIDs) and low dose steroids. In the effective management of RA symptoms, oral corticosteroids are widely used therapy.^[20]

Considering the economic burden of the chronic disease treatment and because of the increased prevalence of the chronic diseases, it is very important to study the drug prescribing pattern of diseases.

So, drug utilization studies are important in evaluation of health care system.So, the clinical pharmacist’s intervention has a positive impact in identifying and managing chronic diseases among patients.^[21]Irrational use of steroids can increase the risk of adverse effects and hence the aim of this study is to improve and ensure patient safety on long term use of corticosteroid by observing the prescribing pattern.

MATERIALS AND METHODS:

A prospective observational study was conducted on 120 patients for 6 months from December 2018 to June 2019 to evaluate drug utilization pattern of corticosteroids. The protocol of the study was approved by Institutional Ethics Committee (IEC) at Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana with ethical clearance number:1316

A data entry format was specially designed which was used to enter patient demographic data (name, age, gender, address), date of admission, date of discharge, patient social history, medication history, past medical history, diagnosis, type of corticosteroid prescribed, dose, side effects. Patients were provided with standardized questionnaires (Modified St. George respiratory questionnaire). The detection and casuality assessment of ADRs is done by Naranjo scale^[22]. The data was collected using suitably designed data collection form during regular ward round in the General Medicine, Respiratory and Orthopedic department.

Finally, the results were analyzed using descriptive statistical methods and were reported to concerned departments.

Study site:

The study was carried out in various department (General Medicine, Respiratory and Orthopedic) of Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala, Haryana.

Inclusion criteria:

Patients of various age groups who received any category of steroid therapy in all the departments of the hospital were included. Inpatients above 18 years receiving corticosteroids therapy and patients willing to participate are included in the study.

Exclusion criteria:

· Patients treated on outpatient basis. Patients under critical condition and requiring critical stay.

· Lactating and nursing mothers. Geriatric population (>60 years).

· Patients not willing to participate were excluded from the study.

RESULTS AND DISCUSSION:

The data was analyzed using descriptive statistical methods and were reported to concerned departments. All subjects satisfy the inclusion and exclusion criteria were included as the study population. 120 subjects enrolled in the study who were prescribed with corticosteroids and admitted to various department of Medicine, Respiratory, and Orthopedic in Maharishi Markandeshwar Institute of Medical Science and Research (MMIMSR), Mullana, Ambala, Haryana.

Age distribution result shows that there were more number of female patients than male in the study population and maximum population belongs to the age group of 51-60 years as discussed in Table1.

Table 1 Gender Categorization of Study Population (n=120)

Gender	COPD	Asthma	RA	Percentage (%)
Male	36	8	11	46%
Female	24	22	19	54%
Total	60	30	30	100%

By analyzing the social history of the patients, it was found that most of the patients 65% were addicted,^[23] and 35% of the population have no addiction as illustrated in Table 2. Subjects were distributed according to area 66% were rural and 34% were urban. Employment status of the patients were analyzed and it was found that 29% patients were employed and 71% were non-employed.

Patients were categorized according to their disease and out of 120 subjects, 60 (50%) were of COPD, 30 (25%) of Asthma and 30 (25%) of Rheumatoid Arthritis as illustrated in Table 2. On evaluation of prescription budesonide (long acting) was commonly prescribed corticosteroid in case of COPD i.e. 45% and in case of asthma it was found to be 76%, followed by duolin (short acting) in case of COPD i.e, 42% and in case of asthma it was found to be 15%, hydrocortisone in case of COPD, 5% and in case of asthma 9%.^[24]In case of RA most commonly prescribed corticosteroid was prednisolone (intermediate acting) (90%) followed by methylprednisolone (10%) as discussed in Table 3.

Table 2 Addiction History and Disease wise distribution of study Population

Addiction History of study Population						Disease wise distribution of study Population
	COPD	Asthma	RA	Total	Percentage (%)	Disease	No. of Patients	Percentage (%)
Smoker	40	09	10	59	42%	COPD	60	50%
Tobacco	11	05	03	19	16%	RA	30	25%
No-Addiction	9	16	17	42	35%	Asthma	30	25%

Patients with mono and dual therapy were found to be 54 and 66. Corticosteroids used in monotherapy were Prednisolone, budesonide and duolin. Combination therapy prescribed were budesonide+ duolin, budesonide + hydrocortisone and prenisolone + methylprednisolone.

In our study the most preferred route of administration in case of COPD and Asthma was nebulizer (80%) and in case of RA the preferred route was oral (92%). This prescribing pattern is comparable to the study in which inhaler administration was found to be highest (44.5%).^[25] The evaluation of proper use of inhaler was done before and after counseling. Patients were provided with standardized questionnaires (Modified St. George respiratory questionnaire) which helped us to evaluate the patient’s knowledge about the proper use of inhaler. The use of inhaler was improved in patients from 55% to 83% after providing counseling regarding the steps followed during inhalation process, nebulizers are most commonly prescribed form of corticosteroids. In case of nebulizer it delivers a fine liquid mist of medication in significantly faster rate to the lungs which provide an effective therapeutic outcome and reduces and reduces the period of hospital stay.^[25] It was found that correct steroids were prescribed to the patients for particular indications.

The study revealed that 76% of the prescriptions were found with drug interactions and 24% were without interactions as illustrated in Table 4. The majority of interactions were minor (72%), followed by moderate (26%) and no severe interaction was found as discussed in Table 4.^[26]

Table 4 Drug interactions and Severity of interactions in study Population

Drug interactions in study Population			Severity of interactions within the study population
Drug interactions in study Population			Severity	Number of interactions	Percentage (%)
Prescription screened	No. of Prescription	Percentage (%)	Minor	21	72%
Prescription with drug interaction	29	24%	Moderate	8	28%
Prescription without drug interaction	91	76%	Severe	0	0

The major concomitant drugs category was antihypertensive (20%), cardiac drugs (18.2%), anti-diabetics (17.5%), gastrointestinal drugs (12.5%), hepatic drugs (8.4%) and others (23.4%) as illustrated in Table 5.

Table 5 Concomitant Drugs observed in the study Population (n=120)

S. No.	Diagnosis	Drug Category	No. of Patients	Percentage (%)
1.	Hypertension	Anti-hypertensive	24	20%
2.	Heart disease	Cardiac drugs	22	18.2%
3.	Diabetes mellitus	Anti-diabetics	21	17.5%
4.	Gastrointestinal disease	Gastrointestinal drugs	15	12.5%
5.	Liver disease	Hepatic drugs	10	8.4%
6.	Others	Other category drugs	28	23.4%

On evaluation of prescription the common side effects due to corticosteroid use were hypertension (28%) followed by hyperglycemia, (24%), sleep disturbance (17%), weight gain (17%), and gastrointestinal (14%) as illustrated in Table 6.

Table 6 Side effects associated with Corticosteroids

Side effects	No. of Patients	Percentage (%)
Hypertension	8	28%
Hyperglycemia	7	24%
Sleep disturbance	5	17%
Weight gain	5	17%
GI upset	4	14%

In our study 3 ADRs were found due to corticosteroids use. Headache was detected in 2 (67%) and facial mooning in 1(33%). By using Naranjo causality assessment scale 1 ADR was possible and 2 ADRs were probable.^[26]

The study outcome reveals that with increase in age of a person, number of diseases increases due to which use of corticosteroid increases.

CONCLUSION:

The present study demonstrates the prescription and utilization pattern of corticosteroids. Amongst the healthcare professionals, not much variation was found in the pattern of prescription of corticosteroids. The study was found to be rational as majority of interactions were minor.

Establishing the social and economic implications of the prescription patterns to the community will shed light in understanding the gap to be filled in this field.

So, we can conclude that involvement of Clinical pharmacist in patient care can help in rational prescribing as well as prevention of drug- drug interactions, side effects and ADRs.

Education of the general public through media programmes and introduction of continuing medical education programmes for medical, paramedical personals and pharmacist which is probably the most important steps to be taken to create awareness about the rational use/ misuse of corticosteroids.

CONFLICT OF INTEREST:

Nil.

ACKNOWLEDGEMENT:

The authors would like to thank all physicians and nursing staff who participated in this study.

REFERENCE:

1. Kendall EC. Nobel lecture: The development of cortisone as therapeutic agent. 2013:21-25.

2. Kendall EC, Reichstein T, Hench SP. Nobel lecture: The development of cortisone as a therapeutic agent. 1950:271-280.

3. Joseph J. What is corticosteroid phobia? Contact magazine news 2013;102-115

4. Tuder RM, Petrache I. Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest 2012:122(8);2749–55.

5. Mathers CD, Loncar D: Projections of global mortality and burden of disease from 2002 to 2030. PLOS Med 2006;3(11):442-8.

6. Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007; 370:765–73.

7. Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;168:968–75.

8. Fujimoto K, Yasuo M, Urushibata K, Hanaoka M, Koizumi T, Kubo K. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease. Eur Respir J 2005;25:640–6.

9. Hurst JR, Perera WR, Wilkinson TMA, Donaldson GC, Wedzicha JA. Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;173:71–8.

10. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung Disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 2017;195(5):557-82.

11. Walters JA, Tan DJ, White CJ, Gibson PG, Wood-Baker R, Walters EH. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014:1288.

12. Suissa S, Barnes PJ. Inhaled corticosteroids in COPD: the case against. European Respiratory Journal 2009;34:13-16.

13. Holgate S.T., Polosa R. Treatment strategies for allergy and asthma. Nat Rev Immunol 2008;8:218–30.

14. Jeffery PK. Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proc Am Thor Soc 2004;1:176–83.

15. Charan NB, Baile EM, Pare PD. Bronchial vascular congestion and angiogenesis. Eur Respir J 1997;10:1173–80.

16. Kumar SD, Emery MJ, Atkins ND, Danta I, Wanner A. Airway mucosal blood flow in bronchial asthma. Am J Respir Crit Care Med 1998;158:153–6.

17. Mendes ES, Campos MA, Hurtado A, Wanner A. Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. Am J Respir Crit Care Med 2004;169:1131–4.

18. Kanazawa H, Asai K, Hirata K, Yoshikawa J. Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma. Chest 2002;122:166–70.

19. Kanazawa H, Nomura S, Yoshikawa J. Role of microvascular permeability on physiologic differences in asthma and eosinophilic bronchitis. Am J Respir Crit Care Med 2004;169:1125–30.

20. Brown RH, Zerhouni EA, Mitzner W. Airway edema potentiates airway reactivity. J Appl Physiol 1995;79:1242–8.

21. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43(2):343-73.

22. Krasselt M, Baerwald C. The current relevance and use of prednisone in rheumatoid arthritis 2014;10(5):557-71.

23. Anusreeraj RS, Prejith P, Diya S, Juliya J, Sivakumar R. A prospective study on drug utilization pattern of glucocorticoids in pulmonology department in a tertiary care teaching hospital. World journal of pharmacy and pharmaceutical science 2016;1511-7.

24. Ference JD, Last AR. Choosing topical corticosteroids. American family Physician. 2009;79(2):51-9.

25. Schweiger TA, Zdanowicz M. Systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Am J Med 2010; 67(13):1061–9.

26. Min KH, Ree CK, Jung JY, Suh MW. Characteristics of Adverse Effects When Using High Dose Short Term Steroid Regimen. Korean J Audiol 2012;16(2):65–70.

Received on 30.10.2019 Modified on 25.12.2019

Research J. Pharm. and Tech. 2020; 13(8):3697-3701.

DOI: 10.5958/0974-360X.2020.00654.X

	Budesonide	Duolin	Hydrocortisone	Methylprednisolone	Prednisolone	Ipratropium Bromide
COPD	45%	42%	5%	8%	0	10%
ASTHMA	76%	15%	9%	0	0	0
RA	0	0	0	10%	90%	0