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To Study the Utilization Pattern of Nasal Decongestants and their Effects on Heart Rate and Blood Pressure
Clinical Rhinology: An International Journal, September-December 2012;5(3):91-94
91
AIJCR
ORIGINAL ARTICLE
To Study the Utilization Pattern of Nasal Decongestants
and their Effects on Heart Rate and Blood Pressure
Harmeet Singh Rehan, Asmita Chopra, Sunil Kumar
ABSTRACT
Background: Nasal decongestants (NDs) are frequently
prescribed over the counter (OTC) drugs for cough and cold.
These are sympathomimetic drugs, which act through 1 and
1 adrenoceptors to cause vasoconstriction and positive
inotropic, chronotropic and dromotropic effect on the heart. This
study was conducted to assess the pattern of utilization of the
NDs and their effect on heart rate (HR) and blood pressure
(BP). Patients were observed for any other adverse drug
reactions (ADRs).
Materials and methods: Randomly 100 prescriptions containing
NDs were collected from the otorhinolaryngology OPD and were
analyzed. All these patients were examined for HR and BP on
day 0, 3 and 7 of administration of NDs. Any ADRs were also
recorded.
Results: Mean ND used per patient was 1.08/patient. Commonly
prescribed NDs were phenylephrine (72.2%), pseudoephedrine
(12.9%), phenylpropanolamine (6.5%), xylometazoline (6.5%)
and oxymetazoline (1.8%). Eight patients received two NDs
orally and/or topically. There was a significant rise in heart rate
on day 7 (p < 0.05). However, the rise in BP was insignificant
both on days 3 and 7. Frequently observed ADR’s included
headache, palpitations and dizziness.
Discussion: Some NDs are known to raise the HR and BP.
Baseline BP monitoring should be done to avoid any further
rise in BP and HR. being an OTC drug there are more chances
of adverse effects of these NDs. It is suggested that NDs should
be prescription only drugs, till adequate evidence is available
regarding their safety.
Keywords: Nasal decongestants, Xylometazoline, Pseudo-
ephedrine, Allergic rhinitis.
How to cite this article: Rehan HS, Chopra A, Kumar S. To
Study the Utilization Pattern of Nasal Decongestants and their
Effects on Heart Rate and Blood Pressure. Clin Rhinol An Int J
2012;5(3):91-94.
Source of support: Nil
Conflict of interest: None declared
INTRODUCTION
Common cold is a frequent and recurrent cause of morbidity
in both adults and children. It commonly manifests with
nasal congestion, which responds to orally or topically
(drops or sprays) administered nasal decongestants
(NDs). The commonly used NDs are phenylephrine,
pseudoephedrine, phenylpropanolamine, oxymetazoline,
xylometazoline, naphazoline, etc.
Oral NDs take approximately 15 to 30 minutes to act,
while the topical ones act much faster. Most of the NDs
stimulate 1 adrenergic receptors, to produce vaso-
constriction of the blood vessels in the nasal mucosa, thus
reducing its swelling and congestion.
The pharmacological effects of NDs are not limited to
the nose, but produce systemic effects also. The orally
administered NDs produce more systemic side effects than
the topically administered ones. Side effects include their
pharmacological effects on the cardiovascular system
through 1 adrenergic agonist action which produces
vasoconstriction and increases peripheral vascular resistance
and 1 adrenergic agonistic action that has a positive
inotropic effect on the heart.1
In 2000, Kernan et al, reported that the anorectic use of
the ND, phenylpropanolamine, is associated with CVA.2 In
view of such reports and the observation of Hemorrhagic
Stroke Project the FDA banned the use of phenyl-
propanolamine in the year 2000.3 However, the safety status
of phenylpropanolamine and other NDs in India is not yet
clear due to the lack of evidence.
Hence, the present study was planned to generate baseline
data on the pattern and safety of use of NDs including their
fixed dose combinations and to evaluate the effect of NDs
on the heart rate (HR) and blood pressure (BP).
MATERIALS AND METHODS
An observational study was conducted to analyze the
prescriptions written by otorhinolaryngologists containing
NDs. Prescriptions were randomly collected outside the
OPD and analyzed for indications for which NDs were
prescribed; concurrently prescribed groups of medicines;
prescription by generic or brand name; type and route of
administration of NDs. Drugs in the fixed dose combinations
(FDCs) were considered as a single drug. Study protocol
was approved by the Institutional Ethical Committee.
All these naive 100 patients, prescribed NDs or fixed
dose combinations containing ND and agreed to participate
in the study, were examined for HR and BP on days 0, 3
and 7. Observed adverse drug reactions (ADRs) recorded
and analyzed for causality using the Naranjo probability
scale.4 Any change in HR and BP after 3 and 7 days of the
use of NDs was compared with the baseline, i.e. day 0 data
using Student’s t-test. A p < 0.05 was considered statistically
significant.
RESULTS
All the 100 patients (52 females and 48 males) whose
prescriptions were collected for analysis participated and
10.5005/jp-journals-10013-1126
Harmeet Singh Rehan et al
92 JAYPEE
completed the study. Mean age of the study patients was
33.57 ± 1.45 years (range, 12-70 years).
Hundred patients were diagnosed with 117 conditions,
14 patients had more than one diagnosis. Commonest
indication for the use of nasal decongestion was rhinitis
(23.9%), followed by chronic suppurative otitis media
(17.9%) and tympanic membrane retraction and congestion
(14.5%; Table 1). All the medicines in this study were
prescribed by brand names. A total of 347 medicines were
prescribed with an average of 3.47 medicines per patient.
FDCs were frequently (67%) used formulations (Table 2).
Commonly prescribed group of drugs along with NDs
(31.1%) were antihistaminics (29%) and NSAIDs (25.9%;
Table 3). A total of 108 ND containing drugs were
prescribed to 100 patients, with an average of 1.08 NDs per
patient. All the oral NDs prescribed were FDCs with
antihistamines and/or NSAIDs (Table 2). Topically used
NDs were single drug preparations containing either
oxymetazoline or xylometazoline. Eight patients received
two NDs concurrently. Majority of the patients received
single oral decongestant (83.3%) and one patient received
two oral FDCs both of which contained an ND each, i.e.
pseudoephedrine and phenylpropanolamine. Seven patients
received oral and topical NDs concurrently. Two patients
received single topical ND. Among the NDs prescribed
phenylephrine was the most frequently prescribed (78%),
followed by pseudoephedrine (Table 4).
Table 1: Diagnosis of the 100 patients receiving NDs
included in the study (N = 117)
Diagnosis No. of diagnosis
Aural 55
CSOM 19
Otomycosis 05
TM retraction 17
Pain and decreased hearing 14
Nasal 44
Rhinitis 28
Nasal blockage 08
Epistaxis 05
Sinusitis 02
DNS 01
Throat 18
Cough 06
Pain and irritation 05
Others 07
Table 2: Type of fixed dose combinations prescribed (N = 128)
Fixed dose combinations No. (%)
Phenylephrine + chlorpheniramine maleate (CPM) 39 (30.4)
Phenylephrine + CPM + paracetamol (PCM) 33 (25.7)
Pseudoephedrine + levocetirizine 13 (10.1)
Clotrimoxazole + chloramphenicol 08 (06.2)
Phenylephrine + ebastine 07 (05.4)
Phenylpropanolamine + PCM + CPM 07 (05.4)
PCM + ibuprofen 05 (03.9)
Other NSAIDs combinations 07 (05.4)
Others 09 (07.0)
Table 3: Frequently prescribed groups of drugs (N = 347)
Groups of drugs No. (%)
Nasal decongestants 108 (31.1)
Antihistamines 101 (29.1)
NSAIDs 90 (25.9)
Antibiotics 26 (07.5)
Other 22 (06.3)
Table 4: Type and frequency of the use of NDs (N = 108)
Nasal decongestants No. (%) of prescriptions*
Phenylephrine 78 (72.2)
Pseudoephedrine 14 (12.9)
Phenylpropanolamine 07 (6.5)
Oxymetazoline 07 (6.5)
Xylometazoline 02 (1.8)
*Eight patients received more than one NDs
Mean baseline HR was 80.79 ± 1.07/min (range, 56-
102/min). It increased to 82.74 ± 1.01/min (range, 63-103/
min) and to 84.33 ± 1.05/min (range, 63-105/min) on days
3 and 7 respectively.
Mean baseline systolic BP was 117 ± 1.09 mm Hg
(range, 92-136 mm Hg). It increased to 119.28 ± 1.12 mm Hg
(range, 96-146 mm Hg) and then to 119.92 ± 1.137 (range,
100-152 mm Hg) on days 3 and 7 respectively.
Mean baseline diastolic BP was 76.16 ± 0.98 mm Hg
(range, 52-78 mm Hg). It increased to 76.88 ± 0.95 mm Hg
(range, 54-96 mm Hg) and then to 77.52 ± 0.97 mm Hg (range,
58-100 mm Hg) on days 3 and 7 respectively (Table 5).
A total of 41 ADRs including headache (17), palpitations
(11), dizziness (5), nasal bleeding (2) and others (6) were
observed. Causality assessment was probable for 22 and
possible for 19 ADRs. Patients who reported increased nasal
bleeding following NDs, subsided itself despite continuation
of NDs.
DISCUSSION
Polypharmacy increases the incidence of ADRs and drug
interactions.5 In this study mean number of drugs per
prescription was 3.47. The mean drug per patient was high
(3.47) in this study. Similarly polypharmacy (3.3-5.7 drugs/
patient) has been reported from Nepal, Nigeria, Indonesia
and India. 5-9
All the drugs (100%) prescribed including NDs were
prescribed by proprietary name and this was higher than
that reported (70.7%) by Rehan et al6 from Nepal, in patients
from all the OPDs. Generic drugs are always costless and
have similar efficacy as the drugs with proprietary names.
Despite having hospital drug formulary and generic
To Study the Utilization Pattern of Nasal Decongestants and their Effects on Heart Rate and Blood Pressure
Clinical Rhinology: An International Journal, September-December 2012;5(3):91-94
93
AIJCR
prescribing policy in this institution use of branded
preparations was high. Prescribers need to be appraised with
benefits of generic prescribing.
In this study, 67% of total drugs prescribed were FDCs
(91.6%; Table 2). None of the FDC’s used in the study was
recommended by the WHO.10 Higher use of FDCs has been
reported by drug utilization studies from both developing9
and developed countries.11 On the contrary, in Nepal, Rehan
et al reported lower use (5.4%) of FDCs. Also, no study
was available to compare the frequency of use of FDCs
containing NDs. FDCs have more disadvantages than
benefits. The patient may not actually need all the drugs in
a combination. The patient is subjected additional side
effects and expense. Also, the freedom to modify the dose
of one ingredient in the combination is lost.12
Frequently prescribed NDs were phenylephrine (78%),
pseudoephedrine (13%) and phenylpropanolamine (7%;
Table 2). Though the prescriptions containing NDs were
only included in the study, but it was observe that eight
patients received two NDs, one received both orally,
whereas others received by oral and topical route. Since
these drugs are sympathomimetic agents, use of more than
one NDs may put the patient at risk of ADRs. There is no
study available to compare these findings.
NDs are sympathomimetic drugs that stimulate and
adrenoceptors. The stimulation of 1 receptors on the
smooth muscles in the blood vessels cause vasoconstriction
leading to decongestion of the nasal mucosa. But along with
1 receptors stimulation, they cause rise in HR and BP.1
This study reported a significant rise in the HR on day 7
of administration of NDs. There was an insignificant rise in
the systolic and diastolic BP on both days 3 and 7 of
administration of NDs. Westerveld et al have also reported
that NDs have dose-dependent inhibitory action on total
iNOS activity which appears to be beneficial because
inducible NO synthase activity may exacerbate the
inflammatory process.13 They also reported that NDs in vitro
appear to have additional benefit in the treatment of upper
respiratory tract infection.
Overall effect of all the NDs caused a significant rise in
HR on day 7 but systolic and diastolic BP showed slight
insignificant rise. Similarly, Hatton et al have reported in a
meta-analysis, that phenylephrine causes a rise in HR and
BP, which is insignificant in a normotensive individual.14
The reason for the significant rise in HR in our study could
be because of the fact that eight patients received two NDs
simultaneously by same or different routes. Use of more
than one ND may not provide additional benefit, as they
act through the same receptor (1), although their adverse
effects are added up. Therefore, it is appropriate to use a
single ND if required.
Empey et al have reported a rise in pulse and systolic
BP with pseudoephedrine at 120 and 180 mg but not with
less than 60 mg.15 Similar to our study, they did not find
any rise in diastolic BP. In our study 30 mg twice daily
dose of pseudoephedrine did not cause any significant rise
in systolic/diastolic BP. Pseudoephedrine in the dose of 60
mg or less may be optimal to achieve maximum nasal
decongestion without cardiovascular and other unwanted
effects.15 In another study, Britton et al reported that
pseudoephedrine is effective in preventing reflex mucoid
congestion after histamine challenge.16
In our study, PPA was the third commonly prescribed
ND (Table 4). PPA is sympathomimetic amine present in
many cough and cold preparations. PPA is also being abused
as an anorectic agent. Many case reports and studies have
discussed the occurrence of intracranial hemorrhage/stroke
after PPA and other NDs.2,17,18 In a Hemorrhagic Stroke
Project, Horwitz et al concluded that the use of PPA
increased the risk of hemorrhagic stroke which subsequently
led to its ban by FDA as a ND and anorectic agent.3
In the present study, HR was significantly increased after
7 days use of NDs whereas insignificant rise in BP,
suggesting their safety with regard to rise in blood pressure
on short term (<7 days) topical administration of NDs.
Systemic review of prospective studies on BP by John and
Frank concluded that safety margin of PPA may decrease
in subjects with patients with elevated basal sympathetic
tone, e.g. overweight patients and patients with slightly
elevated arterial BP.19
Structure of pseudoephedrine resembling amphetamines
due to which they have similar CNS effects, i.e. wakefulness,
alertness and decrease of sense of fatigue and adverse
effects, i.e. headache, dizziness palpitation, etc.1 In our
study, headache, palpitations and dizziness was commonly
observed ADRs, which could be due to the above reason.
In India, no well-planned study is available to establish
the safety of PPA and other NDs. Since NDs are available
Table 5: Effect of NDs on systolic and diastolic BP and HR (mean ± SEM)
Duration HR (beats/min) Systolic BP (mm Hg) Diastolic BP (mm Hg)
Day 0 (baseline) 80.79 ± 1.07 117 ± 1.09 76.16 ± 0.98
Day 3 82.74 ± 1.01 119.28 ± 1.12 76.88 ± 0.95
Day 7 84.33 ± 1.05* 119.92 ± 1.137 77.52 ± 0.97
*p < 0.05
Harmeet Singh Rehan et al
94 JAYPEE
as over the counter drugs and have a potential to cause
cardiovascular and other adverse effects, hence it is
imperative to monitor patient’s baseline HR and BP and
rule out any underlying cardiovascular disease before
prescribing these drugs. In view of lack of safety data of
NDs in India, it is also suggested that NDs should be
available as prescription only drugs till supporting safety
data is available.
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ABOUT THE AUTHORS
Harmeet Singh Rehan (Corresponding Author)
Professor and Head, Department of Pharmacology, Lady Hardinge
Medical College and SSK Hospital, New Delhi, India, e-mail:
harmeetrehan@hotmail.com
Asmita Chopra
Intern, Lady Hardinge Medical College and SSK Hospital, New Delhi
India
Sunil Kumar
Professor, Department of ENT and Otorhinolaryngology, Lady
Hardinge Medical College and SSK Hospital, New Delhi, India
