MS 12003

Review Article
Journal of Pharmaceutical Research Vol. 11, No. 2, April 2012 : 44-48.
A STUDY OF ADVERSE DRUG REACTIONS DUE TO ANTI-
HYPERTENSIVE DRUGS IN DIABETIC PATIENTS IN A MULTISPECIALTY
HOSPITAL
Beulah Samuel *1, Uma Maheswara Reddy C2
1
Vinayaka Mission University, Sankari Main Road, Ariyanoor, Salem 636308, Tamil Nadu, India.
2
Sri. Ramachandra College of Pharmacy, Porur, Chennai 600116, Tamil Nadu, India.
Received on : 03.02.2012 Revised : 12.04.12 Accepted : 17.04.12
ABSTRACT
Adverse drug reactions (ADRs) present a serious public health problem that can affect patients, caregivers,
pharmaceutical companies, and the health care system as a whole. The objective of the present study
was to evaluate Adverse Drug Reactions associated with antihypertensive drugs in diabetic patients. The
present study was an open, non-comparative, observational study done to monitor ADRs associated with
antihypertensive medications in diabetic patients in a multispeciality hospital. A total of 347 adverse drug
reactions were observed in 740 diabetic hypertensive patients during 2008-2010. A high percentage of
ADRs occurred in elderly and female patients. Of the 347 ADRs, 185 (53.3%) were mild, 122 (35.1%)
were moderate and 40 (11.5%) were identified to be severe. Combination therapy was associated with
significantly less occurrence of ADRs, with a total of 147 (42.3%) as compared to monotherapy (n=200,
57.6%). Among the various antihypertensive drugs used in diabetic patients, diuretics were associated
with higher number of ADRs (37.1%), followed by ACE inhibitors (34.2%), beta blockers (18.1%) and
calcium channel blockers (10.3%).
Keywords: Adverse Drug Reaction; Hypertension; Diabetes; Angiotensin-converting enzyme inhibitors;
Beta-blockers.
disease. It is thought that different discontinuation rates
INTRODUCTION for various classes of antihypertensive agents are
High blood pressure (BP) is an important cardiovascular probably related to their different rates of adverse
risk factor. The currently accepted dividing line is symptoms 6-7. Aggressive treatment of hypertension can
systolic BP > or = 140 mm Hg and/or diastolic BP > or reduce cardiovascular events 8.
= 90 mm Hg based on epidemiological and intervention
studies. In India, hypertension has become a major According to the World Health Organization (WHO)
health problem. Epidemiological studies show a steadily definition, an adverse drug reaction (ADR) is ‘a
increasing trend in hypertension prevalence over the response to a drug that is noxious and unintended and
last 40 years, more in urban than in the rural areas 1. occurs at doses normally used in human for the
The frequency of hypertension (HTN) in diabetic prophylaxis, diagnosis, and treatment of disease, or
population is almost twice as compared to non-diabetic for modification of physiological function 9. Adverse drug
general population 2. The coexistence of hypertension reactions (ADRs) are considered among the leading
and diabetes almost doubles the risk of cardiovascular causes of morbidity and mortality. Around 6% of hospital
events 3-4. Patients of both type-1 and type-2 DM are admissions are estimated to be due to ADRs and about
prone to develop hypertension which accelerates 6-15% of hospitalized patients experience a serious
cardiac, renal, and cerebral dysfunctions which are ADR 10.
leading causes of death 5.
When the Food and Drug Administration (FDA)
For the treatment of hypertension in diabetic patients, approves a new drug for marketing, its complete
a broad range of antihypertensive medications are adverse event profile may not be known because of
currently available. Antihypertensive drugs are the limitations of pre-approval clinical trials. Typically,
frequently associated with adverse drug reactions clinical trials for new drugs are of short duration and
(ADRs) that may limit treatment options and reduce are conducted in populations that number from a few
patient compliance, which may hinder blood pressure hundred to several thousand; therefore, the most
control. These drugs are believed to cause ADRs or common dose-related adverse drug reactions are
symptoms that make patients feel worse than they did usually detected in the premarketing phase. Since most
before beginning drug therapy for their “asymptomatic” trials exclude the elderly, children, pregnant women,

*Correspondence : beulah_milton@yahoo.com; profcumr@yahoo.co.in

Journal of Pharmaceutical Research Vol. 11, No. 2, April 2012 : 44
ADVERSE DRUG REACTIONS Beulah Samuel & Uma Maheswara Reddy C
patients with multiple diseases, and those on Table 1: Results of demographic characteristic of the tested
medications suspected of interaction with the study sample (n=740)
drug, the studies’ participants may not be representative
of the real world where the drug is eventually used 11.
An analysis of 192 randomized drug trials found that
the quality and quantity of safety reporting may
sometimes be presented erratically or may be missing
altogether 12. Hence, there is a need to monitor the
safety profile of all the medications on continuous basis
and to review their therapeutic rationale in the light of Gender
add on information emanating out of the adverse drug Table 2 shows the total number of ADRs among the
reaction monitoring activities. Monitoring of ADRs is males and females in the tested sample. It was found
even more important in case of chronic ailments such that a higher percentage of ADRs occurred in females
as hypertension. 190 (54.7%) than males 157 (45.2%).

The objective of this article is to deal with the problems Table 2: Total Number of ADRs among males and females in
of hypertensive drugs in a diabetic patient and to the tested sample
highlight the important role of pharmacist in this task
with the hope that this will stimulate and encourage
increased reporting of serious adverse events
associated with drugs. It is only with the help of alert
and vigilant pharmacists that new risks of drugs are
uncovered. Age
Table 3 shows the total number of ADRs among
MATERIAL AND METHODS
different age groups in the tested sample. A total of
The study protocol was approved by Apollo KH
121 ADRs (34.8%) were observed in the patient age
Institutional Review Board. The study was conducted
group of 61-70 y, followed by 101 (29.1%) in 51-60 y,
between 2008 to 2010 by attending the medicine OPD
78 (22.4%) in 71-80 y, 39 (11.2%) in 41-50 y and 8
on a daily basis. A written informed consent was
(2.3%) of ADRs in 30 - 40 y age groups. The results
obtained from the patients participating in the study. It
show that most of the ADRs were observed in the age
was an open, non-comparative, observational study to
group of 61-70 years.
monitor ADRs associated with antihypertensive
medicines in diabetic patients in a multispecialty Table 3: Total Number of ADRs among different age groups
hospital. All newly diagnosed and old diabetic patients in the tested sample
receiving antihypertensive medications between 30-80
years were included in the study. All mentally
compromised or unconscious patients and patients
unable to respond to verbal questions were excluded
from the study. All drug-related adverse events were
evaluated according to the “WHO Probability
Assessment Scale”. In calculating the ADRs associated
with a specific drug category, a minimum of 6
prescriptions were considered for significant result.
Student’s t test was used for statistical analysis at Severity of ADRs
P<0.05 using Graph Pad Instat software Version 3.06. Table 4 shows the severity of ADRs in the tested
sample. Of the 347 ADRs observed in our study, 40
(11.5%) were identified to be severe, 122 (35.1%) were
RESULTS moderate and 185 (53.3%) were mild. It was found
Demographic characteristics that most of the ADRs observed were of mild severity.
Results of demographic characteristics of the tested Table 4: Severity of ADRs in the tested sample
sample are shown in Table 1. A total of 347 ADRs were
observed in 740 diabetic hypertensive patients (380
male and 360 female) during the two year (2008-2010)
study with a mean age of 61.52±12.10; mean BMI of
61.52±13.90 kg/m2.

Journal of Pharmaceutical Research Vol. 11, No. 2, April 2012 : 45

ADVERSE DRUG REACTIONS Beulah Samuel & Uma Maheswara Reddy C
ADRs among monotherapy and combination Table 7: Type of ADRs due to antihypertensive drugs
therapy observed in the tested sample
Table 5 shows the total number of ADRs among
monotherapy and combination therapy in the tested
sample. It was found that combination therapy was
associated with significantly lesser occurrence of ADRs,
with a total of 147 (42.3%) as compared to monotherapy
(n=200, 57.6%).

Table 5: Total number of ADRs among monotherapy and

combination therapy in the tested sample

WHO probability assessment (causality assess-

ment) scale for ADRs
Table 6 shows the WHO probability assessment scale Table 8: Total Number of diabetic patients experiencing ADRs
for ADRs in the tested sample. On the causality scale due to antihypertensive drugs in the tested sample
of WHO, 61 (17.5%) ADRs were classified certain, 114
(32.8%) probable, 134 (38.6) possible, 14 (4.0%)
unlikely, 4 (1.1%) conditional and 20 (5.7) could not be
categorized (unclassifiable).
Table 6: WHO probability assessment (causality assessment)
scale for ADRs in the tested sample
Classification of antihypertensive drugs associated
with ADRs
Table 9 shows the classification of antihypertensive
drugs associated with ADRs in the tested sample. The
results shows that the most commonly identified ADRs
due to ACE inhibitors was cough in 35 (10.0%) patients,
followed by fatigue in 25 (7.2%), edema in 15 (4.3%),
gastrointestinal tract disease in 12 (3.4%), allergic
reaction in 10 (2.8%), kidney failure in 9 (2.5%), erectile
Type of ADRs due to antihypertensive drugs
dysfunction in 5 (1.4%), head ache in 4 (1.1%),
Table 7 shows the type of ADRs due to antihypertensive
depression in 2 (0.5%) and rash in 2 (0.5%). The most
drugs observed in the tested sample. The results shows
commonly identified ADRs due to beta blockers was
that the most commonly identified ADRs due to
bronchospasm in 20 (5.7%) patients, followed by
antihypertensive drugs in diabetic patients was cold and
fatigue in 15 (4.3%), intermittent claudication in 14
numb hand in 55 (15.8%) patients followed by erectile
(4.0%), erectile dysfunction in 5 (1.4%), gastrointestinal
dysfunction in 42 (12.1%), cough in 41 (11.8%), fatigue
tract disease in 4 (1.1%), head ache in 2 (0.5%),
in 40 (11.5%), edema in 30 (8.6%), kidney failure in 20
allergic reaction in 2 (0.5%), and depression in 1
(5.7%), hyponatremia in 20 (5.7%), bronchospasm in
(0.2%). The most commonly identified ADRs due to
20 (5.7%), gastrointestinal tract disease in 19 (5.4%),
calcium channel blockers was edema in 15 (4.3%)
headache in 14 (4.0%), intermittent claudication in 14
patients, followed by headache in 8 (2.3%), cough in 6
(4.0%), depression in 13 (3.7%), allergic reaction in 12
(1.7%), gastrointestinal tract disease in 3 (0.8%),
(3.4%), hypokalemia in 4 (1.1%) and rash in 3 (0.8%)
erectile dysfunction in 2 (0.5%), kidney failure in 1
patients.
(0.2%) and rash in 1 (0.2%). The most commonly
identified ADRs due to diuretics was cold and numb
Total Number of ADRs due to antihypertensive hand in 55 (15.8%) patients followed by erectile
drugs dysfunction in 30 (8.6%), hyponatremia in 20 (5.7%),
Table 8 shows the total number of ADRs due to kidney failure in 10 (2.8%), depression in 10 (2.8%)
antihypertensive drugs. It was found that among the and hypokalemia in 4 (1.1%).
various antihypertensive drugs used diuretics were
associated with higher number of ADRs (37.1%), DISCUSSION
followed by ACE inhibitors (34.2%), beta blockers In our study for evaluating the ADRs in diabetic patients
(18.1%) and calcium channel blockers (10.3%). receiving anti-hypertensive drugs, a total of 347 ADRs
were observed in 740 diabetic hypertensive patients

Journal of Pharmaceutical Research Vol. 11, No. 2, April 2012 : 46

ADVERSE DRUG REACTIONS Beulah Samuel & Uma Maheswara Reddy C
Table 9: Classification of antihypertensive drugs associated on ACE inhibitors was cough in 35 patients, on beta
with ADRs in the tested sample blockers was bronchospasm in 20 patients, on calcium
channel blockers was edema in 15 patients, and on
diuretics was cold and numb hand in 55 patients.
Previous studies by other researchers were also
similar to our results 20-21.

CONCLUSION
We conclude that, in diabetic hypertensive patients,
intensive control of BP to levels lower than 130/
85mmHg reduces the risk of cardiovascular events. All
4 drug classes—diuretics, beta blockers, ACE
inhibitors, and calcium antagonists were effective in
reducing morbidity and mortality. Most diabetic
hypertensive patients will require combination therapy
during the two year (2008-2010) study. It was found to achieve goal BP. Among the various antihypertensive
that a higher percentage of ADRs occurred in females drugs used, diuretics were associated with higher
than males. The result confirms previous reports that number of ADRs followed by, ACE inhibitors, beta
the occurrence of ADRs is on the higher side in females blockers and calcium channel blockers. Diabetic
13-15
. hypertensive patients are at inevitable risk of bad effects
of drugs due to sub-optimal functionality of their organ
Age was found to be important criteria in the fact that systems. This necessitates careful organ function
the patients in the age group 61 to 70 years experienced analysis prior to prescribing any medication. One of
maximum ADRs followed by patients in the age group the essential reasons of wide prevalence of ADRs in
between 51 to 60 and 71 to 80 years. Previous studies diabetic hypertensive patients is that they are elderly
have also shown that a larger percentage of ADRs was and are often on multiple drug therapy. The results of
reported from geriatric populations which were similar the above study would be useful for the physicians in
to our results 16-17. The severity assessment showed rational selection of drug therapy for treatment of
that 185 ADRs were mild, 122 ADRs were moderate diabetic hypertensive patients. The present data
and 40 ADRs were severe. No lethal effects were suggest that the ADR monitoring needs to be done in
observed or produced. hospital settings continuously so that untoward effect
Combination therapy was associated with significantly caused by different medicines can be identified and
lesser occurrence of ADRs, with a total of 147 as documented.
compared to monotherapy (n=200). In the HOT study,
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