Monitoring Adverse Drug Reactions in Patients of Chronic Obstructive Pulmonary

Disease.
Introduction:
No drug is absolutely safe and an adverse drug reaction (ADR) can occur when it is
administered alone or in combination (Tyagi et al, 200)! According to "#$, an ADR is
defined as %A response to a drug which is noxious and unintended and which occurs at
doses normally used in man for the prophylaxis, diagnosis or therapy for a disease and
for the modification of function excluding failure to accomplish the intended purpose%
(&sch A', ()*2)!
+hronic obstructive ,ulmonary disease (+$-D) is %an obstructive airways disease
characterised by airflow limitation that is not fully reversible. The airflow limitation is
usually progressive and associated with an abnormal inflammatory response of the
lungs to noxious particles or gases% (-etty T., 200/)! 0t includes em,hysema, chronic
bronchitis or a combination of the two 123!
Tobacco use is a 4ey factor, also asthma, e5,osure to air ,ollutants in the home and
wor4,lace, genetic factors, and res,iratory infections ,lay a role in the develo,ment and
,rogression of +$-D 163! +$-D is usually treated with inhaled adrenergic agonists,
inhaled corticosteroids, anticholinergics, oral theo,hylline, oral steroids, antibiotics, and
,oly,harmacy is common 173!
De,ending on the dose, the adverse reactions of anticholinergics causes8 Dry mouth,
thirst, blurred vision, %sandy eyes%, urinary difficultly, and consti,ation 1*3!
And corticosteroids adverse effects range from minor to severe and life threatening! The
nature and severity of it de,ends on the route, dose, fre9uency of administration, and the
s,ecific agent used! The most fre9uent side effects are locally, they include8 $ral
candidiasis, dys,honia, glossitis, hy,er,igmentation of face, hoarseness of voice, sore
throat and throat irritation, and coughing 13!
The classical +ushing:li4e syndrome %redistribution of body fat, moon face, increased
body hair growth, acne, insomnia and increased a,,etite% are observed when e5cess
corticosteroids are ,resent 1*3!
Thera,y does not cure the disease or even significantly slow its ,rogress 1*3, ;o
treatment of +$-D re9uires a careful and thorough evaluation by a ,hysician 163, and
ADR monitoring is absolutely essential for drugs, and thus careful thera,eutic drug
monitoring is re9uired 173!
General obectives:
To monitor adverse drug reactions in ,atients with chronic obstructive ,ulmonary
disease!
!"ecific obectives:
(:<eneral ,rofile of drug treatment and adverse drug reactions for chronic obstructive
,ulmonary disease!
2:=a4ing ,rofile with incidence of adverse drug reactions with inhaled steroids and
anticholinergics in combination of each with adrenergic agonists!
/:Rationali>e drug thera,y according to the adverse effects by ma4ing com,arisons
between different ty,es of drugs used!
2:=easure the effect of smo4ing in the incidence of adverse effects!
6:Differntiation between males and females in the incidence of adverse effects!
7:To increase ,atients awareness of the disease and the adverse reactions to ma4e sure
they can recogni>e it and are aware of the severity of associated ,roblems!

Problem !tatement and #ustification:
ADR are one of the ma?or causes of morbidity and account for nearly 6@ of all hos,ital
admissions all over the world! $ver two million ADRs occur yearly that result in 6@
fatality annually, ADR is the fourth leading cause of death ahead of ,ulmonary disease,
diabetes mellitus, A0D;, ,neumonia and automobile deaths 1)3!
According to "#$ estimates, 0 million ,eo,le have moderate to severe +$-D, more
than / million ,eo,le died of +$-D in 2006, which corres,onds to 6@ of all deaths
globally! 0t is 4nown that almost )0@ of +$-D deaths occur in low: and middle:income
countries 1(03! +$-D 4ills on average one ,erson every (0 seconds 1((3!
+$-D is not one single disease but an umbrella term used to describe chronic lung
diseases that cause limitations in lung airflow! 0t is not a sim,le smo4erAs cough, but an
under:diagnosed, life threatening lung disease! The most common sym,toms of +$-D
are breathlessness, or a %need for air%A, e5cessive s,utum ,roduction, and a chronic
cough 1((3!
The ma?or ris4 factors for +$-D are smo4ing, indoor and outdoor air ,ollution, and the
,lace of wor4, (dusts and chemicals) 1(03!
+$-D is ,reventable, but not curable! Treatment can hel, slow disease ,rogression, but
it generally worsens slowly over time! ;o it is diagnosed fre9uently in ,eo,le aged 20
years or older 1(03! And ADRs may ha,,en for reasons such as alteration in
,harmaco4inetic, ,harmacodynamic, and homeostatic mechanisms related to age which
ma4e them more sensitive to drugs 1(23,and the ty,e and the fre9uency of drugs used
because multi,le drugs used in the treatment of +$-D may result in a variety of ADRs
during thera,y, so this could contribute significantly to morbidity and mortality and it is
im,ortant to monitor ADRs, with an aim to rationali>e drug thera,y in these ,atients 1(3!
Methodology:
Design:
!tudy design:
The study is a ,ros,ective:analytical design!
0t will measure the incidence of adverse drug reactions during thera,y in ,atients of
chronic obstructive ,ulmonary disease!
!etting of the study and !tudy "o"ulation:
The study ,o,ulation are ,atients from both gender (male and female) with chronic
obstructive ,ulmonary disease who attends to hos,itals B <a>a ;tri, :-alestine!
!am"ling si$e:
According to the relationshi, between ;mo4ing and +$-D as ma?or ris4 factor, and
with aid of &,i 0nfo ,rogram to calculate the sam,le si>e of this study, 0 found that one:
9uarter of smo4ers get +$-D in <a>a ;tri, 1(/3! ;o sam,le si>e will be (20 ,artici,ants
by using &,i info ,rogram, ()6@ +onfidence 0nterval, ;tudy ,o,ulation (000)!
!election %diagnostic& criteria:
()Age8 20 years, or older!
2);e58 both gender!
/)Residency8 <a>a ;tri,!
2)Diagnosis8 ,hysical e5amination, clinical and ,ulmonary features (history of smo4ing,
e5ertional dys,noea, cough and e5,ectoration, forced e5,iratory volume in ( sec! is less
than 0@ of the ,redicted value for the ,atients age and height)!
6)&5clusion criteria8 other diseases as (-ulmonary Tuberculosis, any other res,iratory
disorder, Diabetes mellitus, +ongestive heart failure, renal and he,atic dysfunction, and
,regnantClactating females)!
7)0nclusion criteria8 only ,atients with chronic obstructive ,ulmonary disease without
any other diseases or com,lications selected according to diagnosis!
!am"ling method:
=a4ing stratified sam,ling method8
(:-re,are sam,le frame of all +$-D ,atients in hos,itals of <a>a stri, according to
diagnosis!
2:Divide ,atients into grou,s %strata% according to which hos,ital the ,atients belong,
(grou,!(8 Al:;hifa hos,ital, grou,!28 Al:&uro,ean hos,ital D!!)!
/:;elect from each strata the re9uired number Randomly!
De"endent and Inde"endent variables:
'. De"endent variables :
The incidence of adverse drug reactions!
(. Inde"endent variables :
)niversal variables :
(:Age
2:;e5
*ariables related to the study :
(:Ty,e of the drug!
2:+oncentration of the drug, %dose%!
/:'re9uency of drug usage!
2:;eriousnessC;everity of adverse drug reactions!
6:;eriousness of the disease condition!
7:;mo4ing!
*:Ty,e and ,lace of ?ob!
Methods:
The ,atients will be enroll after a written informed consent, for each ,atient, current
medical history, diagnosis, +om,lete blood count (+E+), demogra,hic ,rofile, and
general ,hysical e5amination will done!
+reatment:
-atients will categori>ed into four grou,s, that two grou,s will ta4e combination
thera,y of adrenergic agonist with inhaled anticholinergics, (one will ta4e Tiotro,ium,
and the other will ta4e 0,ratro,ium), and the other two grou,s will ta4e adrenergic
agonist with inhaled steroid, (one will ta4e Eeclomethasone, and the other will ta4e
'luticasone), (the categori>ation, and the choice of drug ty,e will be according to
diagnosis)! The ,atients will follow u, for si5 months every two wee4s during this study
for evaluation of adverse effects of these drugs in ,artici,ated ,atients.
<eneral ,rofile of drug treatment and adverse drug reactions (ADRs) in +$-D8
Drug Given No. of Patient
eceiving the Drug
No. of Patient
!omplaining of AD
, Incidence
0nhaled Anticholinergics
Tiotro,ium
0,ratro,ium
0nhaled ;teroids
Eeclomethasone
'luticasone
Adrenergic Agonists
Total number of ,atients8 (20
-rofile of adverse drug reactions (ADRs) with inhaled steroids, and anticholinergics8
ADR
-rofile
Number of
-atients
with ADRs
@
0ncidence
0nhaled Anticholinergics8
Dry mouth
Thirst
Elurred vision
Frinary difficulty
consti,ation
$thers
0nhaled ;teroids8
$ral candidiasis
Dys,honia
<lossitis
#y,er ,igmentation of face
#oarseness of voice
;ore throat, and throat irritation
+oughing
$thers
Total number of ,atients receiving inhaled anticholinergics8
Total number of ,atients receiving inhaled steroids8
Investigations:
These laboratory tests will carried out if needed!
Allergy tests!
;4in bio,sy!
Elood level!
.iver biochemistry!
Data collection:
Data will be collected from re,orts that written by doctors and nurses from the visits of
,atients to the hos,ital heCshe belongs to, every two wee4s during this study!
Data analysis:
Analysis will be done by using the ;-;; (;tatistical ,ac4age for social science)!
Method of Data analysis:
Analysis of data will be carried out using several tests as8
Chi s-uare test:
Ty,e of the drug
-atients having
ADRs
-atients not having
ADRs
Total
Anticholinergics
;teroids
Total (20

Ty,e of the drug
-atients having
ADRs
-atients not having
ADRs
Total
Tiotro,ium
0,ratro,ium
Total
Ty,e of the drug
-atients having
ADRs
-atients not having
ADRs
Total
Eeclomethasone
'luticasone
Total
Ris4 factor
-atients having
ADRs
-atients not having
ADRs
Total
;mo4ing
Non smo4ing
Total (20
<ender
-atients having
ADRs
-atients not having
ADRs
Total
=ale
'emale
Total (20
.re-uencies statistics/ and chart o"tions:
Ty,e of
Adverse effect
-atients
having
this
adverse
effect
-ercentage
@
Ty,e of drug ma4e
this adverse effect
(anticholinergic from
(to6 grou,%'%,
steroid from 7to(2
grou, %(%)
;tate of
smo4ing
(smo4ingG',
nonG()
<ender
(maleG0,
femaleG')
Dry mouth(')
Thirst(()
Elurred vision(1)
Frinary difficulty(2)
+onsti,ation(3)
$ral candidiasis(4)
Dys,honia(5)
<lossitis(6)
#y,er ,igmentation
of face(7)
#oarseness of voice('0)
;ore throat and throat
irritation('')
+oughing('()
+otal '00,
Also can ma4e t8+est between (-atients having this adverse effect as continuous
variable), and (<ender or ;tate of smo4ing which are categori>ed variables)!
Also can ma4e Recode for the ty,e of adverse effects to grou,s as8
!everity of
Adverse
9umber of Percentage,
+otal
:ffects
"atients
None (no
adverse
effects)%'&
=ild (from (to/
adverse
effects)%(&
=oderate (from
2 to *)%1&
;ever (more
than * adverse
effects)%2&
+otal (20 (00@ (20
+an ma4e .re-uencies statistics and chart o"tions, and A9O*A (between number of
,atients as continuous and severity of the adverse effects)!