Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with ...

Indian Journal of Pharmacy PracticeAssociation of Pharmaceutical Teachers of IndiaStudy of Drug Utilization Pattern of Glucocorticosteroid Drugs withSpecial Emphasis on their Immediate Adverse Effects in a Tertiary CareTeaching Rural Hospital1 2Ankit P* , Bharat G1M.Pharm (Clinical Pharmacy).2Associate Professor, Department of Pharmacology, Pramukhswami Medical College (PSMC), Karamsad, Anand, India.A B S T R A C TSubmitted: 19/7/2010Accepted:15/12/2010To study the utilization pattern of glucocorticosteroid drugs with special emphasis on their adverse effects in a tertiary care teachingrural hospital, attached to a medical college. One hundred patients on glucocorticoids drug therapy in departments of Medicine,Orthopedics, Skin & VD, TB & Chest, Ophthalmology and Paediatrics were randomly recruited in the study. Patients were interviewedand necessary information regarding disease and therapy was collected as per case record form. All these patients were followed uptill their hospital stay. During visits, patients were asked about adverse drug reactions as well as other problems with drug use. Thedata was entered in to SPSS-16 software for statistical analysis. In case records collected from one hundred patients, the totalnumber of drug prescribed were 1081, i.e. a mean of 10.81 drugs per patients in 971 formulations.Out of 1081, two hundred andeighteen (20.17%) were from glucocorticoids group of drugs. Amongst this group, dexamethasone dipropionate (30.28%), budesonide(22.48%), and prednisolone (23.85%) were used predominantly in conditions like bronchial asthma, COPD, bronchiectasis,photodermatitis. In one hundred patients, 92 adverse drug reactions were reported. The most frequent adverse drug reactions observedwere muscular weakness (48.91%) and insomnia (27.17%). Use of glucocorticoid drugs was found appropriate and as per standardguidelines and current protocol of prescribing glucocorticoid drugs. Comparatively, less number of adverse drug reactions wereobserved. However, there is over prescribing of the drugs to the patients. That need a special attention of all doctors and clinicalpharmacists to work together to establish a rational, and practical protocol for clinical conditions.KEY WORDS:- Drug Utilization, Glucocorticoid Drugs , Adverse Drug Reactions.INTRODUCTIONThe use of corticosteroids started some 50 years ago.Being very powerful anti-inflammatory agents, they weredescribed as impressive drugs as they not only improvedcertain clinical conditions, but also conferred a subjectivesense of well-being. Most of the uses of corticosteroidshave been in the fields of rheumatology, orthopedics,dermatology, oncology, respiratory medicine,1otorhinolaryngology (ENT) and ophthalmology.Due to their powerful anti inflammatory andimmunosuppressive actions, these drugs are beingprescribed widely by consultant.This practice has led to over prescribing of these drugsand thereby increased adverse drug reactions. Hence, careAddress for Correspondence:Ankit P, 15, Gangamaiya Colony, N.K.N Road, Nadiad-387001,Gujarat, India.E-mail: justankit1@gmail.comshould be exercised in the selection of corticosteroid drugs foruse as well as their dosage regimen.METHODOLOGYA prospective and observational study was planned toanalyze utilization pattern of glucocorticosteroid drugs inone hundred patients.Inclusion Criteria Patients who receive systemicglucocorticosteroid drugs as their treatment plan;irrespective of diagnosis, age (pediatrics, adults,geriatrics) and sex admitted to wards of departments-Medicine, Orthopedics, Skin & VD, TB & Chest,Ophthalmology and Paediatrics of Shree Krishna Hospital,Karamsad of Anand, India.Prior permission from Human Research Ethics Committeewas taken to conduct the study.Patients were randomly recruited in the study. They wereinterviewed and necessary information regarding theirIndian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 18

Ankit P - Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with Special Emphasis on their Immediate Adverse Effects in a Tertiary Care Teaching Rural Hospitaldiseases and therapy was collected as per case recordform. All these patients were followed up till theirhospital stay. During visits, patients were asked aboutany adverse drug reactions they had developed. Theircase record files were also seen to detect any adversedrug reaction if recorded. For information regardingadverse drug reactions, a check-list was used. Causalityanalysis as per WHO criteria was performed.The data gathered were tabulated in different parameterslike age, sex, diagnosis, no. of drugs/formulationsprescribed, and Adverse Drug reactions due toglucocorticoid drugs observed.The data was entered in to SPSS-16 software forstatistical analysis, Percentage Calculation.RESULTSDemographic parameterAge wise classificationHighest number of patients (68 out of 100) werebelonging to 15 - 60 year age group. While 31 patientswere belonging to age group of more than 60. Onepatient was from 6-14 year age group (Table 1).Sex wise classificationAmongst one hundred patients, 58 were males and 42were females (Table 2).Classification based on diagnosis (system involved) ofpatientsThere were 130 conditions observed in 100 patients. Onedisease condition was observed in 78 patients, where astwo disease conditions (co-morbidity) were observed in 14patients. Eight patients were diagnosed with threeTable1: Age wise classification of patients.Age (in Years) Frequency Percent0-5 0 0.06-14 1 1.015-60 68 68.060+ 31 31.0Total 100 100.0Table 2: Sex wise classification of patients.Sex Frequency PercentMale 58 58.0Female 42 42.0Total 100 100.0different disease condition. The maximum no. of (62 outof 130) (47.69%) conditions were related to therespiratory system (Table 3).Other conditions related to the cardiovascular system,skin, ophthalmology, endocrine system, and joints andbones, were diagnosed as 16 (12.30%), 15 (11.54%),11 (8.46%), 8 (6.15%) and 4 (3.08%) patients respectively.Conditions related to the hepato-biliary, allergy, diseaserelated to the central nervous system, and sclerosis wereseen less frequently (Table 3).Total no. of formulations prescribed to patients indifferent departmentThe total number of drugs prescribed to 100 patientswere 1081 (971 formulations), amongst which 868 drugswere prescribed as single molecule, while 192 drugs wereprescribed as FDCs of two drugs (96x2) and 21 drugswere prescribed as FDCs of three drugs (7x3)[ (868x1)+(96x2)+(7x3) = 1081]It is found that amongst single molecule drugs (868),glucocorticoids were 211 and other drugs were 657 innumber.While amongst fixed dose combinations, 96 fixed dosecombinations with two drugs which did not contain anyglucocorticoid drug and 7 fixed dose combination withTable 3: Classification based on diagnosis / system involved of patientsDiagnosis Frequency PercentRespiratory System 62 47.69Dermatology 15 11.54Joints & Bones 4 3.08Cvs 16 12.31Endocrine 8 6.15Ophtholmology 11 8.46Miscellaneous Hepato- Biliary 2 1.54Cancer 1 0.77Renal 1 0.77Cns 2 1.54Bee Bite 1 0.77Infection 1 0.77Blood 1 0.77Sclerosis 2 1.54Fever(dengue Or Viral) 1 0.77Allergy 2 1.54Total 130 100.00Indian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 19

Ankit P - Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with Special Emphasis on their Immediate Adverse Effects in a Tertiary Care Teaching Rural Hospitalthree drugs which contain one drug as glucocorticoiddrugs (Table 4).Type ofpatientsglucocorticoids drugs prescribed to theIt was found that there were about 13 different types ofglucocorticoid drugs were prescribed.The most frequent type was dexamethasone sodiumphosphate ( 66 out of 218 glucocorticoid drugs) (30.28%),administered via intravenous route.Other widely used glucocorticoid drugs were Budesonide49 (22.48%), Prednisolone 46 (21.10%), and Hydrocortisonesodium succinate 27 (12.39%) in frequency (Table 5).In most prescription, information about strength, durationof treatment, , frequency, route and area of application ( iftopical ) were adequately mentioned, while information onquantity to be used or purchased was inadequate.Adverse Drug Reactions (ADRs) of glucocorticoiddrugs observed in patientsChecklist of common drug reactions with glucocorticoiddrug use was prepared, which contain thirty one differentsymptoms/signs associated with use of these drugs.Out of 31 Adverse drug reactions likely to develop withglucocorticoid drug use, 13 adverse drug reactions wereobserved in our study.Amongst 13 different adverse drug reactions, muscularweakness and insomnia were observed in 45 & 25patients respectively.While the adverse drug reaction like fragile skin andpurple striae, osteoporosis, peptic ulcer, psychosis,hypomania or depression were observed in one patienteach.And adverse drug reaction like hyperglycemia, Cushingsyndrome, heart failure and posterior subcapsular cataractand fever were observed in 3, 4, 2, 2, 5 patientsrespectively (Table 6).DISCUSSIONAge wise distribution of patients shows that maximumnumber of patients were in 15-60 years age group.Amongst them, maximum number of patients weresuffering from condition related to respiratory system.There was no patient in 0-5 years age group, while onlyone patient in 5-14 years age group. It suggest thatpaediatric patients may require less use of glucocorticoiddrugs.Glucocorticoid drugs were maximally utilized in diseaserelated to the respiratory system. Respiratory conditionsare usually allergic and inflammatory, whereglucocorticoid drugs have major role to play. People inthe area are addicted to smoking or tobacco chewing andare therefore more prone to develop respiratoryproblems.Second seat for allergens on our body is skin. In 15 patientssuffering from dermatological conditions, glucocorticoidswere prescribed.In the study by Adrianne C. Feldstein et al, it is reportedthat the most frequent diagnoses associated withglucocorticoid use were chronic obstructive pulmonarydisease, 25.8%; asthma, 21.4%; rheumatoid arthritis,(2)17.2%.Amongst the 100 prescription collected, the total numberof drug prescribed were 1081, i.e. a mean of 10.81 drugsper patient. It is obviously overprescribing.It may be due to patients were suffering from more thanone condition as well as they were having very longhistory of concomitant condition.To counteract common adverse reactions associated withglucocorticoids drug use, anti histaminic drugs andantiemetic drugs were prescribed to these patients, addingtotal number of drugs.Out of 1081 drugs prescribed, two hundred and eighteenwere from glucocorticoid group of drugs. It was foundthat use of the glucocorticoid drugs was rational(according to guidelines), they were used withinappropriate strength and gradually tapered off, switchedfrom parenteral to oral medication.Dexamethasone sodium phosphate by intravenous route washighly prescribed amongst all glucocorticoid drugs. It is dueto its potency and longer duration of action, which playseffective role in acute settings.In spite of large number of prescribed drugs, lowincidence of adverse drug reactions were found in ourstudy.Low incidence is certainly due to rational use ofglucocorticoid drugs. In addition, Patients were followedup to their hospital stay that was maximum 8 days formajority of patients.Indian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 20

Ankit P - Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with Special Emphasis on their Immediate Adverse Effects in a Tertiary Care Teaching Rural HospitalTable 4: Total no. of formulations prescribed to patients in different department.Drugs Single Fixed Dose Fixed DoseTotalMolecule Combination CombinationWith Two With ThreeDrugs DrugsGlucocorticoids 211 0 0 211Other Drugs 657 96 0 753Glucocorticoids + Other Drugs 0 0 7 7Total Formulations 868 96 7 971Total Drugs 868 192 21 1081Table 5. Type of glucocorticoid drugs prescribed to the patients.SRNO.Drug Name Route of Administration Frequency PercentageShort Acting Glucocorticoid Drug1.HydrocortisoneSodium SuccinateIntravenous 27 12.39Intermediate Acting Glucocrticoid DrugsOral2.46 21.10PrednisoloneTopical (Eye) 6 2.75Methyl Prednisolone3.Oral 2 0.91Sodium Succinate4.TriamcinoloneAcetonideTopical (skin)7 3.215. Mometasone Topical (skin) 2 0.91Long Acting Glucocorticoid Drugs6.Dexamethasone SodiumPhosphateIntravenous 66 30.287. Dexamethasone Acetate Topical (skin)1 0.468. Budesonide Inhalation 49 22.489. Clobetasone Butyrate Topical (skin)1 0.4610.Clobetasone-17-PropionateTopical (skin)6 2.7511.BetamethasoneDipropionateTopical (skin)3 1.3712. Desonide Topical (skin)1 0.4613.BeclomethasoneDipropionateTopical (skin)1 0.46Total 218 100.00Indian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 21

Ankit P - Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with Special Emphasis on their Immediate Adverse Effects in a Tertiary Care Teaching Rural HospitalSrNo.Table 6: Adverse Drug Reaction (ADR) of steroid observed in patients.Name of Adverse Drug Reaction Observed in Patients Percent (%)Adverse Drug Reaction from Short Course of Steroid1 Insomnia 25 25.02 Psychosis 1 1.03 Heart Failure 2 2.04 Peptic Ulcer 1 1.05 Hyperglycemia 3 3.0Adverse Drug Reaction from Longer Course of Steroid1 Cushing Syndrome 4 4.02 Fragile Skin And Purple Striae 1 1.03 Ecchymoses 0 0.04 Susceptibility To Infection 0 0.05 Delayed Healing Of Wounds &Surgical Incision 0 0.06 Muscular Weakness 45 45.07 Osteoporosis 1 1.08 Osteonecrosis 0 0.09 Mild Euphoria 0 0.010 Hypomania Or Depression 1 1.011 Hypertension 1 1.012 Glaucoma 0 0.013 Posterior Subcapsular Cataract 2 2.014 Acute Adrenal Insufficiency 0 0.015 Malaise 0 0.063% of patients developed glucocorticoid-type skinchanges and abnormal fat deposition. This wasconsidered the most distressing effect by the patients andwas most frequently seen in women and youngerpatients. Neuropsychiatric disorders, including irritability,anxiety, depression, euphoria, hyperactivity, and manicepisodes, were reported in 52.5%. Skin disorders wereseen in 46.2% of patients, more frequently in women and39% of women described menstrual disorders. Musclecramps and proximal muscle weakness were reported by32.5% and 15% of patients, respectively. New-onset3hypertension developed in 8.7% of patients.In a prospective cohort study of 2108 patients withinflammatory polyarthritis from a community-basedregister at Mayo Clinic, the incidence of hospitalizationfor infection was more than 2.5 times that of the generalpopulation. Use of glucocorticoids was identified as an4independent risk factor for hospitalization for infection.The incidence of various glucocorticoid-associatedadverse events was identified in a large population-basedstudy of over 3 million members of a national managedcare organization, 6517 long-term glucocorticoid users5(>60 days).The adverse event with the greatest prevalence wasweight gain, experienced by 80% of patients in thehighest quartile of glucocorticoid use. Skinbruising/thinning and sleep disturbance were the nextmost commonly reported adverse events. Cataracts (15%overall) and fractures (12% overall) were reported less6frequently but were still common.In our study, most frequent adverse drug reactionobserved were muscular weakness and insomnia. Butthese come under possible category, because samesymptoms are very common in elderly group of patientsdue to co-morbid conditions.CONCLUSIONIn the study, use of glucocorticoid drugs were appropriateand according to standard guideline and current protocolof prescribing glucocorticoid drugs. Obviously, lessnumber of adverse drug reaction were observed.However, there is over prescribing of the drugs to theIndian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 22

Ankit P - Study of Drug Utilization Pattern of Glucocorticosteroid Drugs with Special Emphasis on their Immediate Adverse Effects in a Tertiary Care Teaching Rural Hospitalpatients. That need a special attention of all doctors andclinical pharmacist to work together to establish arational, and practical protocol for clinical conditions.ACKNOWLEDGEMENTSOur sincere and warm thanks to CEO, H.M Patel centrefor Medical care & Education for giving us permission toconduct the study in Shree Krishna Hospital.We also express thanks to head of all departments, allconsultants and patients of Shree Krishna hospital, weretimely help had made this project possible.REFERENCES1. Goodman & Gilman's: The pharmacological basis ofththerapeutics. 11 ed. 2006.2. Feldstein Adrianne C, Elmer Patricia J, Nichols GregoryA, Herson Michael. Practice patterns in patients at risk forglucocorticoid-induced osteoporosis. OsteoporosisInternational 2005 Dec;16:2168–74.3. Fardet L, Flahault A, Kettaneh A. Corticosteroid-inducedclinical adverse events: Frequency, risk factors andpatient's opinion. Br J Dermatol 2007;157:142–48.4. Franklin J, Lunt M, Bunn D. Risk and predictors ofinfection leading to hospitalization in a large primarycare-derivedcohort of patients with inflammatorypolyarthritis. Ann Rheum Dis 2007;66:308–12.5. Angeli A, Guglielmi G, Dovio A. High prevalence ofasymptomatic vertebral fractures in postmenopausalwomen receiving chronic glucocorticoid therapy: Across-sectional outpatient study. Bone 2006;39:253–59.6. Curtis JR, Westfall AO, Allison J. Population-basedassessment of adverse events associated with long-termglucocorticoid use. Arthritis Rheum 2006;55:420–26.Indian Journal of Pharmacy Practice Volume 3 Issue 4 Oct - Dec, 2010 23