Drug utilization study of anti-hypertensive drugs and

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Drug utilization study of anti-hypertensive drugs and
RESEARCH PAPER
Drug utilization study of anti-hypertensive drugs
and their adverse effects in patients of a tertiary care
hospital
Krunal C. Solanki, Rusva A. Mistry, 1Anil P. Singh, Shilpa P. Jadav, Nirav M. Patel, Hiren R.
Trivedi
Department of Pharmacology, M.P. Shah Government Medical College, Jamnagar, Gujarat. 1 Department of Pharmacology,
P.D.U. Government Medical College, Rajkot, India.
Correspondence address: Dr. Krunal C. Solanki, Department of Pharmacology, M.P. Shah Government Medical College,
Jamnagar-361008, India. E-mail: [email protected]
DOI: 10.5455/jcer.201334
___________________________________________________________________________________________
ABSTRACT
Background: Hypertension is one of the leading causes of cardiovascular disease. Though many clinical guidelines
published recently for the treatment of hypertension, there is substantial variation in the treatment of hypertension in
different countries. Aims and objectives: To evaluate the drug utilization pattern among hypertensive patients and
their adverse effects attending medicine OPD in a tertiary care teaching hospital. Materials and Methods: A
prospective, observational study was conducted by Department of Pharmacology in a tertiary care teaching hospital
over a period of six months. The diagnosis and line of treatment to be given was decided by the physician in charge of
the Department of Medicine. All the information of ADR was recorded in CDSCO Suspected ADR reporting form.
Results: Out of 600 patients, 43.83% were male and 56.17% were female. Maximum patients belonged to age group
of 51-60 years (33.5%). Diabetes mellitus (40.33%) was the most common associated disease with hypertension.
About half of the patients had received two antihypertensive drugs (49.50%), followed by one (33.16%) and three
(15.5%) antihypertensive drugs. Enalapril was the most commonly prescribed antihypertensive drug (79.66%). 95
patients (15.83%) from the total of 600 patients developed ADR. Most common ADR was cough (18.94%) followed
by headache (12.63%) and vomiting (10.52%). Enalapril was responsible for about half of the ADR (50.52%)
followed by amlodipine (25.26%) and furosemide (25.26%). Conclusion: Rational utilization pattern of
antihypertensive drugs was observed. However diuretics and calcium channel blockers prescribed less commonly.
Most of the ADRs were probable (55.79%) and mild (30.53%).
Key words: Adverse drug reaction, drug utilization pattern, hypertension
___________________________________________________________________________________________
INTRODUCTION
Hypertension is an important public health challenge
in both economically developing and developed
countries. In India, cardiovascular diseases (CVDs)
are estimated to be responsible for 1.5 million deaths
annually.[1] Hypertension is a major risk factor for
CVDs, including stroke and myocardial infarction,
and its burden is increasing disproportionately in
developing countries as they undergo demographic
transition.[2]
A number of national and international guidelines
for the treatment of hypertension have been
published. JNC 7 guideline recommends diuretics as
the first-line treatment in hypertension.[3] The
European guideline, on the other hand, suggests that
unless a special indication exists, any of the five
antihypertensive classes can be used as first-line
treatment.[4] The National Institute for Health and
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Solanki, et al.: Drug utilization and pharmacovigilance of antihypertensive drugs
Clinical Excellence (NICE) guideline[5] recommend
angiotensin-converting enzyme (ACE) inhibitor or
angiotensin-II receptor blocker (ARB) as step 1
antihypertensive treatment aged under 55 years,
whereas calcium channel blockers (CCBs) are
preferred step 1 antihypertensive treatment aged
over 55 years. A combination treatment has recently
been recommended as first-line intervention,
particularly in patients with severe hypertension.[3,4]
Changes over time in terms of recommended
guidelines and innovations in drug formulations
have resulted in modifications in prescription pattern
of antihypertensive drugs in different countries.
Monitoring of prescriptions and drug utilization
studies could identify the associated problems and
provide feedback to prescriber.[6] Developing
countries have limited funds available for healthcare
and drugs and it becomes very important to prescribe
drug rationally so that the available funds can be
utilized optimally.[7] Drug utilization studies are
powerful exploratory tools to ascertain the role of
drugs in society. They create a sound socio-medical
and healthy economic basis for healthcare decision
making.[8]
Drugs are double edged weapons. Drugs, no matter
how safe and efficacious, are always coupled with
inescapable risk of adverse reactions. Thus, drug
safety assessment should be considered as an
integral part of day to day clinical practice. Adverse
drug reactions (ADRs) are considered among the
leading causes of morbidity and mortality.
Monitoring of ADRs is more important in case of
chronic ailments such as hypertension. More often
than not, hypertension is an asymptomatic disorder
and requires long term therapy predisposing to
adverse drug events.[9]
The objective of present study was to focus on the
trends in the drug utilization of antihypertensive
drugs and to evaluate the clinical spectrum of all
ADRs of antihypertensive drugs in the outpatients
attending the Dept. of Medicine. It also emphasises
the need and importance of an effective
pharmacovigilance programme.
Primary objectives:
of our tertiary care teaching hospital, using
WHO drug use indicators.
2. To assess the incidence of adverse drug
reactions of antihypertensive drugs.
Secondary objectives:
1. To observe the demographic pattern of
hypertensive patients.
2. To observe the effect of concurrent disease on
hypertensive treatment.
3. To analyse the average cost of treatment for all
drugs and antihypertensive drugs alone.
4. To assess causality of offending drugs.
5. To assess severity and preventability of reported
adverse drug reactions.
MATERIALS AND METHODS
A prospective, observational study was conducted
by Department of Pharmacology in association with
Department of Medicine in a Guru Gobindsinh
Government hospital, Jamnagar. The study was
conducted over a period of 6 months from Dec 2011May 2012 after approval from Institutional Ethics
Committee. The diagnosis and line of treatment to
be given was decided by the physician in charge of
the Department of Medicine. No additional drugs or
investigations were advised by us during the study
period. Data of patients matching inclusion criteria
were recorded after getting informed consent.
Identity of patient was kept confidential.
 Selection criteria of patients
Inclusion Criteria
1. Patients with hypertension, of both sex and all
age groups, who were prescribed an
antihypertensive drug in medicine OPD.
2. Patients referred from other department who
reported on OPD basis.
Exclusion Criteria
1. Patients who reported in OPD and were
subsequently admitted.
2. Patients with hypertensive emergency &
hypertensive urgency.
1. To identify drug prescribing pattern among
hypertensive patients attending medicine OPD
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3. Patient with any concurrent acute medical
condition. e.g., acute myocardial infarction,
acute left ventricular failure etc.
patients belonged to age group of 51-60 years201(33.5%), followed by 61-70 years- 156(26%) and
41-50 years-130(21.67%). Mean age in study subject
was 56.74±11.23 years.
Sample size
WHO recommends a sample size of at least 600
encounters for drug utilization studies (WHO how to
investigate drug use in health facilities, 1993).[10]
Based on above recommendation, we used a sample
size consisting of 600 patients.
Collection of Data
Data of patients matching inclusion criteria were
recorded. Before including in the study, patients
were explained about the aspects of research work.
Written informed consent was taken before
including him or her into the study. Once the
consultation by the physician was over, the
prescriptions were copied and patients were
interviewed
regarding duration
of
taking
antihypertensive drugs and detail of adverse drug
reaction if developed. Data like name, age, sex,
duration of hypertension, family history, vital data,
general examination, laboratory investigation,
concurrent diseases, and ongoing treatment was
recorded from patient’s case. These data were
recorded in previously prepared case record forms.
Total 600 cases were collected. Patients were
included from all the six units of medicine. The
diagnosis of the ADR was done by a consultant
physician based on clinical and laboratory
investigation data. ADR was defined as per the
definition provided by WHO (1972).[11] All the
information of ADR was carefully recorded in
CDSCO Suspected ADR reporting form. Causality,
Severity and preventability of ADR were assessed
by WHO causality assessment scale[12], Hartwig and
Siegel severity assessment scale[13] and Schumock
and Thornton preventability scale[14] respectively.
All the data were compiled and subjected to
descriptive statistical analysis using mean and
standard deviation in Graph pad prism.
RESULTS
Out of 600 patients, 263(43.83%) were male and 337
(56.17%) were female respectively. Maximum
Majority of the patients were suffering from concurrent
diabetes mellitus (40.33%). Other commonly
associated conditions were angina (5.33%), COPD
(5%), IHD (3.83%) and epilepsy (3.5%).
In current study, about half of the patients had received
two antihypertensive drugs (49.50%), followed by one
(33.16%) and three (15.5%) antihypertensive drugs
[Table 1]. Patients having diabetes along with
hypertension had received two antihypertensive drugs
(47.34%) most commonly, followed by one (35.51%)
and three (15.91%) antihypertensive drugs.
Table 1: Number of antihypertensive drugs
prescribed per encounter
No. of drugs
No. of patients (%, n=600)
1
199 (33.16%)
2
297 (49.50%)
3
93 (15.5%)
4
11 (1.83%)
In this study, 82% patients had received 3 or more
drugs. 88.44% of patients had more than 5 years of
duration of hypertension as compared to 77.36% of
patients who had less than 5 years duration of
hypertension. The average number of antihypertensive
drugs per encounter was 1.86±0.73 with range of 1 to
4. The average number of drugs per encounter was
4.01±1.61 with range of 1 to 10.
Among the antihypertensive drugs, enalapril (ACE
inhibitor) was the most commonly prescribed drug
(79.66%) followed by atenolol (beta blocker)
(49.66%), amlodipine(CCB) (33.83%), furosemide
(loop diuretic) (17%) and metoprolol (beta blocker)
(4.66%). Antidiabetic drugs were prescribed to 40.83%
of patients. Among them, metformin was the most
commonly prescribed drug (32.33%) followed by
glibenclaimide (25.16%), insulin (7.50%), pioglitazone
(5.83%), voglibose (2.33%) and acarbose(1.66%).
Antiplatelets (aspirin and clopidogrel) were prescribed
to 40.66% of patients. The statins (atorvastatin) were
prescribed only to a small proportion of patients
(8.33%). Other drugs prescribed were paracetamol
(12.33%), cetrizine (10.33%), vitamins B complex and
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folic acid (9.83%), famotidine (9.66%) and alprazolam
(6%) [Table 2].
Table 2 : Commonly used drug groups in study
subjects
Drugs
Antihypertensive drugs
Enalapril (ACE inhibitor)
Atenolol (Beta blocker)
Amlodipine (Calcium channel
blocker)
Furosemide (Loop diuretic)
Metoprolol (Beta blocker)
Losartan (Angiotensin antagonist)
Antidiabetic drugs
Metformin (biguanides)
Glibenclaimide (Sulphonylureas)
Insulin
Pioglitazone (Thiazolidinediones)
Voglibose (α-glucosidase
inhibitors)
Acarbose (α-glucosidase
inhibitors)
Antiplatelet drugs
Aspirin
Clopidogrel
Others
Paracetamol
Cetrizine
Famotidine
Atorvastatin
Alprazolam
B complex
No. of patients (%,
n=600)
478 (79.66%)
298 (49.66%)
203 (33.83%)
102 (17%)
28 (4.66%)
5 (0.83%)
194 (32.33%)
151 (25.16%)
45 (7.50%)
35 (5.83%)
14 (2.33%)
Three drugs were prescribed in 15.50% of patients.
13.46% patients with diabetes were received three
drugs. Enalapril + atenolol + amlodipine was most
commonly prescribed combination (8%) followed by
enalapril + atenolol + furosemide (4.16%) and enalapril
+ amlodipine + furosemide (1.66%). Same utilization
pattern was observed in patient of diabetes [Table 3].
Four drugs were prescribed in 1.83% of patients.
Enalapril + atenolol + amlodipine + furosemide were
most commonly prescribed combination (1.66%).
Same combination was prescribed in patients of
diabetes (1.22%) [Table 3].
Table 3: Utilization pattern of different
antihypertensive drugs
No. of drug
10 (1.66%)
218 (36.33%)
26 (4.33%)
74 (12.33%)
62 (10.33%)
58 (9.66%)
50 (8.33%)
36 (6%)
36 (6%)
In present study 33.16% of patients had received single
drug for the treatment of hypertension. 33.47% of
diabetic patients associated with hypertension had
received single drug for treatment. Enalapril was the
most commonly used drug (21.16%) followed by
atenolol (6.83%) and amlodipine (4.5%). Same
utilization pattern was observed in patients of diabetes
who had received enalapril (24.89%) most common
drug followed by atenolol (5.30%) and amlodipine
(3.26%) [Table 3].
Two drugs were prescribed in 49.50% of patients.
46.53% patients with diabetes were received two
drugs. Enalapril + atenolol was most commonly
prescribed combination (22%) followed by enalapril +
amlodipine (10.83%) and enalapril + furosemide
(5.33%). Same utilization pattern was observed in
patient of diabetes who had received enalapril +
atenolol combination (20.40%) followed by enalapril +
amlodipine (9.79%) and enalapril + furosemide
(5.71%) [Table 3].
Single drug
Enalapril
Atenolol
Amlodipine
Two drugs
Enalapril + Atenolol
Enalapril + Amlodipine
Enalapril + Furosemide
Atenolol + Amlodipine
Enalapril + Metoprolol
Others
Three drugs
Enalapril + Atenolol +
Amlodipine
Enalapril + Atenolol +
Furosemide
Enalapril + Amlodipine +
Furosemide
Others
Four drugs
Enalapril + Atenolol +
Amlodipine +
Furosemide
Enalapril + Atenolol +
Losartan + Furosemide
No. of patients
No. of
patients with
Total No. of
diabetes
patients (%,
mellitus
n=600)
(%, n=245)
61 (24.89%)
13 (5.30%)
8 (3.26%)
127 (21.16%)
41 (6.83%)
27 (4.50%)
50 (20.40%)
24 (9.79%)
14 (5.71%)
13 (5.30%)
4 (1.63%)
9 (3.67%)
132 (22%)
65 (10.83%)
32 (5.33%)
28 (4.66%)
17 (2.83%)
23 (3.83%)
17 (6.94%)
48 (8%)
9 (3.67%)
25 (4.16%)
3 (1.22%)
10 (1.66%)
4 (1.63%)
10 (1.66%)
3 (1.22%)
10 (1.66%)
0
1 (0.16%)
In present study, 1785 drugs were prescribed by
generic name and 620 drugs were given by brand
name. So, 74.22% drugs were given by generic name
and 25.78% were given by brand name.Out of 43 drugs
used, 32(74.41%) drugs were prescribed from National
list of essential medicines of India, 2011 and 33
(76.74%) drugs were prescribed from essential drug list
of Gujarat, 2010-11.
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In present study at each encounter antihypertensive
drugs were prescribed for 30 days. Average cost of
antihypertensive drugs per encounter was ` 137.69
and average cost per encounter of all drugs including
antihypertensive drugs was ` 243.33. The percentage
of drug costs spent on antihypertensive was 56.58%.
The cost was calculated according to minimum price of
that drug in IDR, March-April 2012.
In current study prescribed daily dose of
antihypertensive drugs are as follows- enalapril (10.14
mg), atenolol (80.37 mg), amlodipine (8.91 mg),
furosemide (49.41 mg) and metoprolol (91.07 mg).
PDD: DDD ratio ranged between 0.607-1.782 with
amlodipine having maximum ratio (1.782) followed by
furosemide (1.235), atenolol (1.071) and enalapril
(1.014) [Table 4].
Table 4: ATC, and PDD:DDD of
antihypertensive drugs
Drug
Enalapril
Atenolol
Amlodipine
Furosemide
Metoprolol
ATC code
C09AA02
C07AB03
C03CA01
C08CA01
C07AB02
PDD
10.14 mg
80.37 mg
8.91 mg
49.41 mg
91.07 mg
PDD:DDD ratio
1.014
1.071
1.782
1.235
0.607
In present study 95 patients (15.83%) from the total of
600 patients developed ADR. Among them 48
(50.52%) were male and 47 (49.48%) were female. In
male ADRs were observed most commonly in age
group of 61-70 years (18.94%) followed by 51-60
years (15.78%) and 41-50 years (8.42%). Same age
group pattern observed in female in which ADRs most
commonly occurred in age group of 61-70 years
(18.94%) followed by 51-60 years (15.78%) and 41-50
years (8.42%) [Figure 1].
In present study most common SOC (System Organ
Class) of ADRs involved was nervous system
disorders (23.15%) followed by respiratory, thoracic
and mediastinal disorders (18.94%), gastrointestinal
disorders (15.78%) and general disorders and
administration site disorders (13.68%). Most common
ADR according to preferred term (PT) was cough
(18.94%) followed by headache (12.63%), vomiting
(10.52%), oedema
peripheral (8.42%) and
maculopapular rash (7.36%) [Table 5].
Figure 1: Age and sex distribution of ADR
In current study enalapril was responsible for about
half of the ADR (50.52%) followed by amlodipine
(25.26%), furosemide (25.26%) and atenolol (14.73%).
Enalapril was mainly responsible for dry cough
(18.94%) followed by gastrointestinal adverse effects
(9.47%) and rash (7.36%). Most common ADR of
amlodipine was headache (9.47%) followed by ankle
edema (8.42%) and palpitation (6.31%). Most common
ADR of furosemide was gastrointestinal adverse
effects (9.47%) followed by fatigue and numbness
(8.42%) and dizziness (5.26%). Atenolol was mainly
responsible for bradycardia (6.31%) followed by
hyperkalemia (3.15%) and headache (2.10%).
According to WHO causality assessment scale most of
ADRs were “probable” (55.79%) followed by
“possible” (35.79%) and certain (8.42%).
According to Hartwig and Siegel severity assessment
scale 30.53% ADRs were “mild” and 69.47% ADRs
were “moderate”.
According to Schumock and Thornton preventability
scale 8.42% ADRs were “preventable” while 91.58%
ADRs were “not preventable”.
DISCUSSION
Hypertension is a chronic disease requiring lifelong
treatment. Although lifestyle modifications play an
important role in hypertension management, drugs
become unavoidable in many patients. This study
analysed the prescription pattern in hypertensive
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patients attending the outpatient department in a
tertiary care hospital attached to our institute.
In present study 263 (43.83%) patients were male and
diabetes (40.33%). Other associated conditions were
angina (5.33%), COPD (5%), IHD (3.83%) and
epilepsy (3.5%). Study conducted by Pai et al[15]
reported diabetes mellitus (47.5%), ischemic heart
Table 5: Classification of ADRs according to system organ class and preferred terms
System organ class
No. of ADR (%,
n=95)
Nervous system disorders
22 (23.15%)
Respiratory, thoracic and mediastinal disorders
18 (18.94%)
Gastrointestinal disorders
15 (15.78%)
General disorders and administration site disorders
13 (13.68%)
Cardiac disorders
12 (12.63%)
Skin and subcutaneous tissue disorders
7 (7.36%)
Metabolism and nutrition disorders
5 (5.26%)
Vascular disorders
3 (3.16%)
337 (56.17%) patients were female. Study conducted
by Pai et al[15] reported 50.5% male and 40.5% female.
Other study by Sandozi and Emani[16] has found 47%
male and 53% female and Queen Mary Utilization of
Antihypertensive Drugs Study (QUADS)[17] conducted
in 2004 observed 48% male and 52% female in the
study.
Most common age group involved in our study was 5160 years (33.5%), followed by 61-70 years (26%) and
41-50 years (21.67%). Tiwari et al[18] also found most
common age group 50-59 years (33.3%) followed by
60-69 years and 40-49 years(26.7%). Study conducted
by Pai et al[15] reported most common age group 60-69
years (34%) followed by 70-79 years (23%) and 40-49
years (22%).
In current study, mean age of study subjects were
56.74±11.23 years with 58.11±10.94 years in male and
55.66±11.35 years in female. Pai et al[15] found mean
age in study subject 63.1 years with 62.72 years in
male and 63.48 years in female. Etuk et al[19] found
mean age in study subject 52.3±14.6 years.
Patients with chronic diseases like hypertension usually
suffer from other associated conditions. In our study,
majority of the patients were suffering from concurrent
Preferred term
No. of ADR (%)
Headache
Dizziness
Hypoasthesia
Cough
12 (12.63%)
6 (6.31%)
4 (4.21%)
18 (18.94%)
Vomiting
Diarrhoea
Oedema peripheral
Fatigue
Palpitation
Bradycardia
Rash, maculopapular
10 (10.52%)
5 (5.26%)
8 (8.42%)
5 (5.26%)
6 (6.31%)
6 (6.31%)
7 (7.36%)
Hyperkalemia
Hypokalemia
Hypotension
3 (3.16%)
2 (2.10%)
3 (3.16%)
disease (16.5%), hyperlipidemia (18%), renal diseases
(7.5%) & cardiovascular accidents (16%) concurrently.
Sakthi S et al[20] reported diabetes mellitus(35%) as
the most frequent co-morbidity followed by
asthma(5%) and ischemic heart disease(1.6%). Such
patients are at greater risk of developing complications.
Among the various diseases, cardiovascular diseases
pose a major threat. Multiple drugs are required for
their management. Polypharmacy is associated with a
high cost, increased risk of side effects, drug
interaction and noncompliance.[21]
In current study, the average number of
antihypertensive drugs per encounter was 1.86±0.73
with range of 1 to 4. QUADS[17] conducted in 2004 has
reported 2.0±0.06 antihypertensive drugs per
encounter. The average number of drugs per encounter
was 4.01±1.61 in our study with range of 1 to 10.
Sandozi and Emani[16] has reported 4.68 drugs per
prescription and Akici et al[22] has reported 3.8±1.1
drugs per prescription. The observed difference might
be because of different demographic profile of study
patients, different prescribing practices and availability
of drugs. Because hypertension is associated with
various concurrent diseases and its complications,
polypharmacy is quite prevalent.
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Solanki, et al.: Drug utilization and pharmacovigilance of antihypertensive drugs
In this study, the number of drugs prescribed to patients
is more for those who had longer duration of
hypertension. 82% patients had received 3 or more
drugs. 88.44% of patients who had more than 5 years
of duration of hypertension had received 3 or more
different drugs as compared to 77.36% of patients who
had less than 5 years duration of hypertension. As the
disease progresses, it is difficult to control the blood
pressure and it requires combination of drugs.
Among the antihypertensive drugs, enalapril (ACE
inhibitor) was the most commonly prescribed drug
(79.66%) followed by atenolol (beta blocker)
(49.66%), amlodipine (CCB) (33.83%), furosemide
(loop diuretic) (17%) and metoprolol (Beta blocker)
(4.66%). This is in consonance with study conducted
by Sandozi and Emani[16] reported ACEIs (47%) were
most commonly prescribed drug followed by CCBs
(25.85%), beta blockers (12%), angiotensin receptor
blockers (10.8%) and diuretics (3.7%). Other study
conducted in India by Pai et al[15] reported calcium
channel blockers (49%) were the most commonly
prescribed drugs followed by diuretics (43.5%),
angiotensin converting enzyme inhibitors (29.5%) beta
blockers (29%), angiotensin receptor blockers (21%),
alpha adrenergic blockers (2%) and central
sympatholytics (2%). QUADS[17] reported CCB
(65%) were the most commonly prescribed drugs
followed by beta blockers (64%) and ACEIs (33%).
This difference might be due to physician’s choice with
relation to the characteristics of patients, their
concurrent illness, as well as the availability of
medicines.
In present study enalapril (74.69%) was the most
commonly prescribed antihypertensive drug in patients
of associated diabetes mellitus followed by atenolol
(41.63%), amlodipine (29.39%) and furosemide
(13.06%). However, Pai et al[15] reported that diuretics
(43.1%) were the leading class of drugs followed by
the ACEI (40%), CCB (29.5%), beta blockers (26.3%)
and ARB (17.9%) in patients of associated diabetes
mellitus. Akici et al[16] found CCB (35.5%) were the
leading class of drugs followed by the ACEI (25.8%),
diuretics (9.7%) and beta blockers (9.7%) in diabetic
patient.
In present study about half of the patients had received
two antihypertensive drugs (49.50%), followed by one
(33.16%), three (15.5%) and four (1.83%)
antihypertensive drugs. Pai et al[15] reported
monotherapy (49%) as most commonly prescribed
pattern followed by two (34.5%), three (14%) and
four drug (2.5%) regimen antihypertensive therapy.
Etuk et al[19] found two drug combination (49.30%)
most commonly followed by three (26.38%) one
(20.13%) and four (94.16%) drug antihypertensive
regimen.
Present study found enalapril + atenolol was most
commonly prescribed two drug combinations (22%)
followed by enalapril + amlodipine (10.83%) and
enalapril + furosemide (5.33%). Pai et al[15] found ARB
with diuretic (25.4%) was the most frequently
prescribed two drug combination followed by a
combination of two diuretics (10.8%) and CCB with
beta blockers (9.8%). Etuk et al[19] reported ACEI and
diuretic (19.44%) most common two drug combination
followed by central sympatholytic and diuretic
(11.11%) and CCB and diuretic (9.72%).
This study found enalapril + atenolol + amlodipine as
most commonly prescribed three drug combinations
(8%) followed by enalapril + atenolol + furosemide
(4.16%) and enalapril + amlodipine + furosemide
(1.66%). Etuk et al[19] reported ACEI + diuretic +
central sympatholytic (13.88%) most commonly
prescribed three drug combinations followed by ACEI
+ diuretic + CCB (4.16%) and ACEI + diuretic + beta
blocker (3.47%).
In present study enalapril + atenolol + amlodipine +
furosemide was most commonly prescribed four drug
combination (1.66%). Etuk et al[19] reported ACEI +
diuretic + CCB+ central sympatholytic (2.77%) as
most commonly prescribed four drug combination.
The present study observed that multiple drug therapy
(66.84%) was more common than single drug therapy
(33.16%). These results supports the work of Hansson
et al[15] reported that blood pressure could be
adequately controlled with the help of combination
therapy. Furthermore combination therapy seems to be
a rational approach to reduce the cardiovascular
mortality.[4]
Diuretics are the recommended first-line treatment in
the US (JNC VII)[3] guidelines. However, UK National
Institute for Health and Clinical Excellence (NICE)
guideline[5] on the management of primary
hypertension in adults recommend angiotensinconverting enzyme (ACE) inhibitor or a low-cost
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Solanki, et al.: Drug utilization and pharmacovigilance of antihypertensive drugs
angiotensin-II receptor blocker (ARB) as step 1
antihypertensive treatment aged under 55 years. While
calcium channel blockers (CCBs) is preferred step 1
antihypertensive treatment aged over 55 years and
advise that thiazide-like diuretics should only be used
first line if CCBs are not suitable or if the patient has
edema or has a high risk of developing heart failure. In
our study diuretic (17%) and CCB (33.83%) were
prescribed less frequently.
In this study, 74.22% drugs were given by generic
name and 25.78% were given by brand name. It is
clearly evident that more than 2/3rd of drugs were
prescribed by generic name and therefore drug use in
this set up is quite rational. Increasing generic
prescribing would rationalize the use and reduce the
cost of drugs.[23]
Out of 43 drugs used, 32 (74.41%) drugs were
prescribed from National list of essential medicines of
India, 2011 and 33 (76.74%) drugs were prescribed
from essential drug list of Gujarat, 2010-11, which
points towards rational prescription practices. Use of
drugs from the essential drug list should be promoted
for optimal use of limited financial resources, to have
acceptable safety and to satisfy the health needs of the
majority of the population.
In present study antihypertensive drugs were
prescribed for 30 days at each encounter. Average cost
of antihypertensive drugs per encounter was ` 137.69
and average cost per encounter of all drugs including
antihypertensive drugs was ` 243.33. The percentage
of drug costs spent on antihypertensive is 56.58%. It is
relatively higher in the study conducted in India by Jhaj
et al[24] and Sandozi and Emani.[16] The higher cost in
these studies is due to more drugs were prescribed by
brand name as compared to generic name. Cost of
prescription is important in chronic disease like
hypertension. One of the better approaches to decrease
the prescription cost is to prescribe cheaper brands.
Since hypertension is a long term disease and drug has
to be continued for life time, there is a reasonable scope
in reducing the prescription cost by prescribing cheaper
alternatives.
In current study prescribed daily dose of various
antihypertensive drugs observed are as followsenalapril (10.14 mg), atenolol (80.37 mg), amlodipine
(8.91 mg), furosemide (49.41 mg) and metoprolol
(91.07 mg). PDD:DDD ratio ranged between 0.607-
1.782 with amlodipine (CCB) having maximum ratio
(1.782) followed by furosemide (loop diuretics)
(1.235), atenolol (beta blockers) (1.071) and enalapril
(1.014). Our result concluded that PDD:DDD for
atenolol and enalapril is approximately 1 indicative of
appropriate utilization pattern of these drugs. While
PDD:DDD ratio of amlodipine (1.782) and furosemide
(1.235)
suggest
overutilization
of
these
antihypertensive drugs. Grimmsmann and Himmel[25]
reported ACEIs had most notable PDD:DDD ratio
(2.17), followed by the ARBs (1.88), CCB (1.51),
thiazide diuretics (1) and beta blockers (0.84). Factors
such as the severity of the hypertension or the doctor’s
dissatisfaction with the efficacy of a drug may lead to a
change of drugs or change of dose-seem to be
responsible for alteration of PDD:DDD ratio.
In present study 95 patients (15.83%) from the total of
600 patients developed ADR. Among them 48
(50.52%) were male and 47 (49.48%) were female.
Our result is in consonance with Hussain et al[26] which
reported ADR in 13.60% patients and Alomar and
Strauch[27] reported ADR in 14.25% of patients.
Hussain et al[26] found higher percentage of ADRs in
females (58.8%) than males (41.2%).
In current study, ADRs were observed most commonly
in age group of 61-70 years (37.89%) followed by 5160 years (28.42%) and 41-50 years (17.89%). Hussain
et al[26] observed most common age group 41-50 years
(35.3%), followed by 51-60 years (26.5%) and 61-70
years (26.5%).
In current study most common SOC (System Organ
Class) of ADRs involved was nervous system
disorders (23.15%) followed by respiratory, thoracic
and mediastinal disorders (18.94%), gastrointestinal
disorders (15.78%) and general disorders and
administration site disorders (13.68%). The previous
studies by Hussain et al[26] reported cardiac disorders
to be most frequent cause of ADRs (35.3%) followed
by gastrointestinal disorders (20.6%).
In present study most common individual ADR was
cough (18.94%) followed by headache (12.63%),
vomiting (10.52%), peripheral oedema (8.42%) and
maculopapular rash (7.36%). Our results are in
accordance with Hussain et al[26], reported cough as
most common ADR followed by peripheral oedema,
headache and hypotension. While Alomar and
Strauch[27] found headache as most common ADR
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Solanki, et al.: Drug utilization and pharmacovigilance of antihypertensive drugs
followed by gastrointestinal adverse reaction, fatigue
and numbness, dizziness and oedema. Different type
of ADRs observed is due to different prescription
pattern of antihypertensive drugs in the study.
In current study enalapril (ACEIs) was responsible for
about half of the ADR (50.52%) followed by
amlodipine (CCB) (25.26%), furosemide (Diuretics)
(25.26%) and atenolol (Beta blockers) (14.73%). This
result is different with previous studies by Hussain et
al[26] reported beta blockers (32.35%) is the most
common group responsible for ADR followed by CCB
(26.47%) and ACE inhibitors (14.70%) whereas Basak
et al[28] reported CCB (38.01%) as most common
group responsible for ADR followed by ACE
inhibitors (23.14%) and beta blockers (21.07%). This
difference is due to differences in prescription pattern
of antihypertensive drugs in our study and these two
studies.
In present study according to WHO causality
assessment scale most of ADRs were “probable”
(55.79%) followed by “possible” (35.79%) and
“certain” (8.42%). Hussain et al[26] found most
common ADRs were “possible” (47.1%), followed by
“probable” (35.5%) and “certain” (2.9%). In our study
most of ADRs were “probable” which suggest that
these ADRs are due to antihypertensive drugs and are
unlikely to be attributed to concurrent disease or other
drugs or chemicals, and follows a clinically reasonable
response
on
withdrawal
(dechallenge)
of
antihypertensive drugs. “Possible” ADRs of
antihypertensive drugs could also be explained by
concurrent disease or other drugs or chemicals. While
“certain” ADRs intimate that antihypertensive drugs
are responsible for ADRs and it cannot be explained by
concurrent disease or other drugs or chemicals. Also
the response to withdrawal of the drug (dechallenge) is
clinically plausible and the event is definitive
pharmacologically using a satisfactory rechallenge if
necessary.
According to Hartwig and Siegel severity assessment
scale 30.53% ADRs were “mild” and 69.47% were
“moderate” in our study whereas 52.9% ADRs were
“mild”, 41.2% were “moderate” and 5.8% were
“severe” in Hussain et al[26] study.
Duration of present study was six month, which is one
limitation of the study. Long duration of study may
provide further information regarding utilization
pattern and other rare adverse drug reaction of
antihypertensive drugs.
CONCLUSION
This study provided a baseline data regarding the
prescribing pattern in hypertensive patients. There is a
scope for improvement, particularly the under
utilization of diuretics and calcium channel blocker in
the present drug utilization study of hypertension.
Since hypertension is a common lifelong disorder,
prescription cost is one of the major reasons for nonadherence to drug therapy. One of the important factors
which affect compliance of patient and drug adherence
is the presence of the adverse drug reactions. Further
studies from time to time are required in drug
utilization pattern and standard treatment guidelines to
be circulated among prescribing physician.
ACKNOWLEDGEMENT
We are very thankful to all the professors and staff
members and particularly Dr Hemang Aacharya,
MD, Professor and Head of Department of
Medicine, M.P. Shah Government Medical College,
Jamnagar for their kind cooperation and valuable
suggestion for successful completion of study.
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Cite this article as: Solanki KC, Mistry RA, Singh AP, Jadav SP,
Patel NM, Trivedi HR. Drug utilization study of anti-hypertensive
drugs and their adverse effects in patients of a tertiary care
hospital. J Clin Exp Res 2013;1:58-67.
Source of Support: Nil, Conflicts of Interest: None declared
Journal of Clinical & Experimental ResearchSeptember-December 2013Volume 1Issue 3
67

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