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Department of Pharmacology
Vallabhbhai Patel Chest Institute
University of Delhi, Delhi-110007

SOPI-2010, LHMC, New Delhi, 27/11/2010,


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V response to a drug that is u   u
uuu and that occurs at doses used in
humans for prophylaxis, diagnosis, or therapy
of disease, or for the modification of
physiologic function

V xcludes therapeutic failures, overdose, drug


abuse, non-compliance, and medication
errors
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V DR contribute significantly to the morbidity and


mortality and increased health costs

V Over 2 million serious DRs per year,


responsible for 5% of hospital admissions,
1,00,000 deaths yearly

V DRs :leading cause of morbidity, ahead of lung


disease, diabetes, IDS, Trauma
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V India : 4th largest producer of the pharmaceuticals in the
world
V Drugs prescribed (sometimes indiscriminately and
irrationally) in various combinations (polypharmacy)
V Large sections of population exposed
V DR contribute significantly to the morbidity and
mortality and increased health costs
V Clinical trial data not sufficient
V dire need for a scientific/systematic and uniform
method to monitor DRs
    
 

V Spontaneous reports (most commonly)

V PM (prescription event monitoring)

V Observational Studies(Case Control and Cohort


Studies)
h
   


V Unsolicited communication by health care


professionals or consumers to a company,
regulatory authority or any other organization
(WHO, Regional Centers) that describes one or
more dverse Drug Reactions in patient who
was given one or more medicinal products

V It does not derive from a study or any organized


data collection scheme



Hutchison defined causality assessment as a


³method for eliciting a state of information about
a particular drug-event connection as input and
delivering as output a degree of belief about the
truth of the proposition that the drug caused the
event to occur´

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V Naranjo¶s scale

V WHO causality assessment scale



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V Prior reports of reaction


V Temporal relationship
V De-challenge
V Re-challenge
V Dose-response relationship
V lternative etiologies
V Past history of reaction to same or similar
medication
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V
 
 

V Respiratory diseases : a major cause of hospital


admissions
V Obstructive airway disease (Bronchial sthma
and COPD) affect 5-7% population in
industrialized countries
V Several factors (allergy and smoking) contribute
to their genesis
V Optimization and rationalization of drug therapy :
key to effective management
 
 

V Drug therapy involves polypharmacy


V Multiple routes of drug administration ±
sometimes in the same individual
V Complex drug ± drug interactions always a
possibility
V Long term drug usage compounds the problem
V Drugs with narrow therapeutic indices
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V 120 patients of bronchial asthma and COPD


were selected from the VPCI OPD
V thical clearance and GCP guidelines
V Standard inclusion/exclusion criteria
V Diagnosed by clinical features and PFT findings
V DR profile was recorded as per National
Pharmacovigilance Programme proforma
V Dechallenge and rechallenge were done
wherever appropriate
V Causality ssessment was done by using the
Naranjo`s scale
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|  
 
 
Drugs Br sthma COPD Profile
Inhaled steroids 54/60 (90%) 30/60 (50%) Sore
throat,dysguesia,
hoarseness,gloss
itis, others
Inhaled 25/40 (62%) 10/44 (23%) Dry mouth,thirst,
anticholinergics urinary difficulty

Inhaled beta-2 15/35 (43%) 3/55 (5%) Hand tremors


agonists(S )
Oral steroids 28/32 (87%) 3/14 (21%) Wt gain, acne,
cramps, mood
changes
Oral 14/20 (70%) 20/43 (46%) nxiety,
theophylline dyspepsia, mus
spasm,
paresthesia, etc


V Most DRs : mild to moderate, few were intolerable
and required dose reduction ( oral steroid and
theophylline)
V 75% of patients complained of one or other DR
V 23 % of COPD patients and 53 % of bronchial asthma
patients required oral steroids
V Oral steroids were associated with incidence of DRs -
21% (in COPD) and 87% (in br asthma)
V 84 of total patients received inhaled anticholinergics out
of which DRs were noted in 41% patients
  
V Bronchodilators and corticosteroids are the
mainstay in the treatment of O Ds
V Recently a resurgence in the interest in
theophylline due to anti-inflammatory and
immunomodulatory effects reported
V Low doses (lower than those needed to induce
bronchodilation) exert beneficial effects
V /udicious use could be of benefit in O D in
developing countries (reduces dose of steroids
and a pharmacoeconomically viable drug
  

   


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ADR No. of Patients Percentage
Dyspepsia 13 65%
Anxiety 12 60%
Spasm of Muscles 6 30%
Insomnia 2 10%
Dizziness 2 10%
Theophylline Withdrawal Induced 1 5%
Constipation

Paraesthesia 2 10%
Others 1 5%
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v  5 
Kighly Probable Possible Doubtful
Probable (9) (5-8) (1-4) (0)

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V prospective, open label, randomized, parallel design
study was carried out to compare the efficacy and safety
of two methylxanthines, namely theophylline and
doxofylline in patients of bronchial asthma and COPD

V total of 60 patients, 30 each of bronchial asthma and


COPD were enrolled for the study as per the laid down
inclusion and exclusion criteria

V ach group of 30 patients received standard treatment


for asthma and COPD
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anxiety

Muscle spasm
Dizziness
Sore throat
No DRs
insomnia

No DR
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anxiety anxiety

Muscle spasm Dry mouth

insomnia Tremors

Gastritis Nausea

No DR No DRs
h
V Doxofylline was more therapeutically effective than
theophylline in COPD

V DR profiles of theophylline and doxofylline included


dyspepsia, anxiety, muscle spasm, tremors,
dizziness, and headache

V Doxofylline treated group was associated with lesser


frequency of DRs as compared to the theophylline
group

V Such focussed studies will be helpful in rationalizing


drug therapy in O D
cknowledgements
V Dr V K Vijayan
V Prof Ray
V Dr Neeraj Tyagi
V Dr Gaurav Vishnoi
V Dr Dushyant Lal