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Submitted by
Doctor of Pharmacy
(2011-2016)
DEPARTMENT OF PHARMACY
UNIVERSITY OF MALAKAND
I dedicate my project report to my parents who faced a lot of troubles
to serve me and my friends specially all of my university class
fellows and my well-wishers with whom I completed this task and
spent a lovely time....
2
APPROVAL CERTIFICATE
It is certified that Mr. Afsar Ali Khan has completed his clinical Pharmacy Clerkship
at Saidu Teaching Hospitals, Swat on the title Chronic Obstructive Pulmonary
Disease for the partial fulfilment of the degree of Doctor of Pharmacy (Pharm. D).
SUPERVISED BY:
_______________________
Dr. M. Junaid
Associate professor,
Department of Pharmacy,
University of Malakand.
EXTERNAL EXAMINER:
________________________
CHAIRMAN:
_________________________
3
CONTENTS
ACKNOWLDGMENT ............................................................................................................ 5
Abbreviation table ................................................................................................................... 6
Aims and objectives ................................................................................................................. 8
Summary ................................................................................................................................... 9
Introduction ............................................................................................................................ 10
Methodology ........................................................................................................................... 18
Case histories .......................................................................................................................... 20
Case: 1 .................................................................................................................................. 20
Case 2 ................................................................................................................................... 23
Case 3 ................................................................................................................................... 25
Case 4 ................................................................................................................................... 28
Case 5 ................................................................................................................................... 30
Case 6 ................................................................................................................................... 32
Case 7 ................................................................................................................................... 35
Case 8 ................................................................................................................................... 37
Case 9 ................................................................................................................................... 40
Case: 10 ................................................................................................................................ 43
Conclusion .............................................................................................................................. 50
References ............................................................................................................................... 51
4
ACKNOWLDGMENT
I expend my Heart full thanks and appreciation to Mr. Muhammad Yousaf chief
pharmacist Saidu group of teaching hospitals and Dr.fawad Ali due to their kind
support during wards rounds and data collection.
Last but not the least my parents for whom I have no words of acknowledgment to
express my gratitude and emotions. My success and all the abilities are due to their
kindness, their parenting skills, their guidance and their prayers. May Allah give them
a long and happy life and give me the ability to make them happy and to serve
humanity.
5
Abbreviation table
Word Abbreviation
Gm Gram
HCT Hematocrate
HTN Hypertension
I/v Intravenous
INF Infusion
INJ Injection
L Litre
mg Milligram
6
N.M not mentioned
NEB Nebulizer/nebulisation
OD once daily
P/O Oral
SYP Syrup
TAB Tablet
7
Aims and objectives
2) To detect, collect, report and discuss data about rational therapy of COPD in
Saidu group of teaching hospitals, Swat.
8
Summary
COPD is the chronic disease of lungs which consist of two pathological conditions.
Bronchitis and emphysema, due to these conditions obstructions occur to air passage
in the lungs and the patient feel signs of dyspnoea, productive cough, weight loss and
fever. WHO estimates it as the 3rd leading cause of deaths and fifth leading cause of
disability by 2020.Worldwide approximately ten to twenty percent of the population
whose age is more than 40 years and makes round about 80 million people are
effected with COPD and contributing to 3 million deaths per year. So for treatment of
COPD the drugs most commonly used are bronchodilators including 2 adrenergic
agonists like salbutamol, anticholinergic like ipatropium methyl xanthenes like
theophyline .along with these inhaled corticosteroids, antibiotics and oxygen therapy
are the options for treatment.
The main causes of this disease include cigarette smoking. Dust, fumes, and smokes
may be also the leading causative factors for COPD.
Smoking is considered to be the most common cause of COPD but the cases
evaluated during this study shows that six patients out of ten were not smokers but
were coal workers and two in ten patients were smokers.
This project was completed in the medical ward-B of Saidu teaching hospital Swat.
Total 10 cases have been discussed in detail and to collect data and record histories of
COPD patients, I designed a Performa which include the personal information,
Medical and surgical history, complaints of patient ward level medication, medication
prescribed for home ADRs and drug interactions .at the end of each case I also had
given my comments and suggestions.
I felt intense need of clinical pharmacist at wards because I noted many drug
interactions and lack of patience compliance.
So pharmacist should be present in the ward to counsel the patients and guide the
prescribers and patients regarding the drugs and its use.
9
Introduction
Epidemiology
[14]
COPD is the fourth leading cause of deaths in the United States while WHO
estimates as the third leading cause of deaths and fifth leading cause of disability by
2020[13].Worldwide approximately ten to twenty percent of the population whose age
is more than 40 years and makes round about eighty million people are effected with
COPD and contributing to three million deaths per year [17, 18]. A survey whose results
were displayed by Asian Pacific Society of Respiratory Diseases 6.2 percent of COPD
patients in the world are found in 11 Asian countries [19].
10
Mortality rate of COPD
A graph of data given by WHO which show the mortality rate of COPD in males and
females on the base of age is given below [20].
11
Etiology of COPD
There may be a number of causes for COPD but cigarette smoking is the main cause
[5]
of COPD and majority of COPD patients found are smokers and the patients who
smokes, are twelve to thirteen times more prone and susceptible to death than that of
[6, 7].
non smoker patients Other than cigarette other harmful and irritating gases,
genetic factors, dusts, pollutants ,previous history of pulmonary infections in
childhood, and the socioeconomic conditions of the patients are also risk factors and
may be counted as the causes of COPD [8].
Due to genetic deficiency the body fails to produce a protein called Alpha-1
antitrypsin [AAT], which is responsible for the protection of lungs, leads to
emphysema and COPD [9].The risk factors are also discussed as under.
12
tools or early diagnosis and treatment of COPD are at high risk of sever
COPD.
Oxidative stress: lungs are directly damaged by the imbalance between
oxidants and anti oxidants and leads to lung inflammation [20].
Relentless cough with sputum production ,the sputum may also have blood
Dyspnoea (difficulty or shortness of breath) for months or even long time
Cyanosis in severe case
Weight loss
Fever
Diagnosis of COPD
COPD is diagnosed on the basis of physical analysis of signs and symptoms, taking
patient medical record and considering risk factors. Diagnostic tests play an important
role in the determination of disease, in which some test should be done for all
suspected like patients spirometry while some should conducted on special population
like alpha-1 AAT deficiency test. The most important one is FEV (forced expiratory
volume) test .COPD is also classified into different stages on the basis of FEV1 and
ratio of FEV1/FVC.
Upon the results of spirometry COPD is classified into four main types which are
shown as [21, 23].
13
Along with test other techniques may also be conducted for diagnosis of COPD which
may include bronchodilator reversibility test and six minutes walk test, chest
radiography, arterial blood gas analysis and full blood count [20, 22].
Pathophysiology in COPD
A patient suffering from COPD has actually abnormality or damage in four parts of
lungs which are central airways, peripheral airways parenchyma cells of the lungs and
pulmonary vasculature [24]. These abnormalities may due to mainly smoking but other
foreign harmful particles like smoke dust and fumes may cause these abnormalities
which irritate the mucosa of lung which in turns increase the numbers of neutrophils
,macrophages and CD8+ lymphocytes which mediates inflammation and also by these
imbalances and irritation and break down and repair of alveoli, hyper inflation of
lungs occur which give flatness to the diaphragm and make the rib cage larger than
normal in the lung occurs.[,25,27] which results increase secretions of mucus and
difficulty in expiration i.e. shortness of breath dyspnoea and productive cough , and
imbalance in the gases exchanges and pulmonary hypertension which may result cor
pulmonale [26,28].
Management of COPD
COPD is a curable and preventable disease. The main objective of the management is
the dilation of air ways. The pre management plan for COPD is to stop cigarette
smoking and prevention from fumes, smokes, dust and other irritating gases and
prevention from exacerbation of the disease by earlier diagnosis and treatment [29].
Pharmacotherapy of COPD
Pharmacotherapy of COPD means the use and management of disease through
medicines. The aim of therapy is to reduce exacerbation and also to relieve the
symptoms of the patient, in case of COPD the route of administration which is
preferred is inhalatory route because that has proven to be the most effective.
The major classes of drugs used in the treatment of COPD are [30],
Bronchodilators
Corticosteroids
Antibiotics
Oxygen therapy
Along with these agents mucolytics are also useful in COPD. [31] Bronchodilators
further have many classes i.e. 2 agonists, anti cholinergic and xanthenes derivatives.
14
2 agonists have further two classes i.e. short acting and long acting 2 agonists.
Bronchodilators
inhaled carticosteriods
pulmonary rehabilitation
Oxygen therapy
Bronchodilators
Bronchodilators are the main class of drugs used for COPD. This class include
adrenergic agonists i.e. beta 2 adrenergic agonists, methyl xanthenes and anti
cholinergic.
2 agonists
2 agonists are the drugs which are used more frequently for the treatment of COPD
they may be short acting or long acting also known as SABA and LABA respectively.
Mechanism of Action
They act on 2 receptors present in the smooth muscles of lungs. They interact with
the G protein and produce the cyclic AMP which in turn stimulate protein kinase A
and which is responsible for phosphorylation and hence relaxation of smooth muscles
occurs. The exact targets are unknown but it is believed that it involves protein kinase
and calcium dependent potassium channels [34].
15
Short acting 2 agonists (SABA)
SABA are very helpful in the management of COPD and studies shows that if a
patient use SABA for regular a week so his lung function can be improved and
dyspnoea may also be reduced [35]. Combination of two SABAs is proven to be more
effective than the single one drug [36].
Albuterol is the drug of this class which is frequently and mostly used. These drugs
show their effect within five minutes and its reach to maximum rate only in 15
minutes and total duration of time is almost 4 hours.the other examples includes the
drugs namely levosulbutamol terbutaline levelbuterol, metaproterenol. Retodrine and
pirbuterol,
Long acting 2 agonists also used for bronchodilator effect with good efficacy and are
first line drugs in treatment of COPD but their duration of action is longer than the
short acting and their effect remains up to twelve hours so the frequency of dose are
low in this case and hence therapy cost also becomes low.
Adverse effects
Usually on low therapeutic doses no sever adverse effects occurs but some patients
may also report adverse effects like tachycardia, .hypokalemia Tremors or
nervousness even on low doses and specially the use of these agents should be made
with conscious and more care in the patients of diabetes mellitus and heart diseases
and albuterol is contra indicated in Cardiac tachyarrhythmia. [6.52]
Combination of 2 agonists and anti cholinergic drugs shows more effective results in
the treatment of COPD.
Methyl xanthenes
Theophyline and aminophyline are the examples of this class of bronchodilators .they
block the phosphodiesterase enzymes competitively and inhibit inflammatory
mediators and thus are useful in bronchodilaton and reducing the bronchitis. They are
16
given orally or parentally but the dose strength should be properly monitored because
they are drugs having narrow therapeutic index.
Inhaled corticosteroids
They reduce the inflammation of airways in the lungs and helpful in COPD the
commonly used corticosteroids in COPD are bechlomethasone, dexamethasone,
fluticasone and budesonide.
These agents alone are not effective but are prescribed in combination with
bronchodilators for good results and smoothing of lung muscles.
Oxygen therapy
The patients having exacerbation of COPD are often found to be cyanosed and having
severe dyspnea so for those patients immediate oxygen therapy required .the
haemoglobin level of such patients is also high because not enough oxygen can reach
the body so body produce more haemoglobin . Oxygen therapy is the emergency
based option of therapy for COPD.
Expectorants
Expectorants are generally used for the reduction of productive cough in the patients
and for soothing effect. The mucolytics agents are generally used and the dosage form
used is syrups.
17
Methodology
For compilation of my internship project report and proper record of patients
medication history, I had to interview the patients and ask some questions from them
so for that I designed a Performa which served as a base for my whole study regarding
the patient and medicines used for the treatment of patients of COPD. The Performa
contain the following important information.
Address............................................................Addiction...................
Chief complaints (signs and symptoms with which patient was admitted)
1
2
3
4
5
Diagnostic tests advised
Test Result Test Result
Previous medication record for this disease (medicines used before admitted at
hospital)
18
Ward level medication (treatment of patient in hospital)
Date......................
Date......................
Dosage form Trade name Generic name strength route Frequency
Response to therapy (how the patient feels after using the medicines? is the patient
satisfied or is the condition of patient improving or no)?
Complaints with current therapy (any complaint from patient side due to use of the
drugs it include side effects or conditions due to drugs interactions)
Drug interactions if any (drug interactions which may possibly exist between the
prescribed drugs)
19
Case histories
Case: 1
Name: A1 Age: 80 years Sex: Male
Ward: MMW-B Bed number: 20 physician: Dr.Fayaz
Address: Kohistan Addiction: snuffing only
Admission date: 22-8-2016
Chief complaints
1 SOB (shortness of breath)
2 chest pain
3 legs pain
4 cyanosed
5 congested eyes
Diagnosis
COPD
Conjunctivitis
Cor pulmonale
20
Tab Prostreate Tamsulosin 0.4mg oral OD
Inj Lasix furosemide 40mg I/v Stat
Tab Loprin aspirin 75mg oral OD
Inh Oxygen Oxygen therapy - inhalation -
Same therapy was continued and following drugs were added to the previous therapy
Same therapy was continued as the previous day and one more drug was added to
therapy plan which is
Cap Synasma Doxophylline 400mg oral OD
Same therapy continued as the last day and venesection was done along
with these remedies which were added to therapy,
Ventolin (sulbutamol) ...nebulizer...... QID
INJ... leflox (levofloxicin)...........I/v.... OD
Same therapy was continued to the patient and after 7 days injection
levofloxicin was stopped.
Response to therapy
Medicines are effective and show good response
21
Complaints with current therapy
Heart burn
22
Case 2
Chief complaints
1. Fever for 1 week
2. SOB (seasonal more in winter) from last 10 years
3 Joints pains
4 Insomnia
5 loss of appetite
Diagnostic tests advised
Test Result Test Result
CXR B.urea 31 mg/dl
Diagnosis
COPD
NO
23
Inj Decodran dexamethasone 2cc I/V B.D
Neb Ventoline sulbutamol 2cc neb OD
Medication prescribed for home
Response to therapy
Not satisfactory
24
Case 3
Name: A3 Age: 40 years Sex: male
Chief complaints
1. SOB
2. Chest pain
3. Oedema
4. Productive cough
Diagnosis
COPD
25
Ward level medication
Same therapy was continued and addition of following drugs was done
26
Tab Spiromide Spironolactone.fu 20mg p/o OD
rosamide
Tab Calzam daltiazim 30 mg p/o OD
Tab Leflox levofloxicin 500mg p/o 1 for 10 days
Response to therapy
Not satisfactory on first 2 days but later on patient was feeling well with the therapy
27
Case 4
Chief complaints
1. SOB
2. Wheezing chest sound
3. Weight loss/ weakness
Diagnosis
COPD
HTN
28
Neb Ventoline sulbutamol 2cc neb Tds
Tab Ascard plus aspirin 75mg p/o OD
Inh arotec sulbutamol 200mcg inh 2 puffs sos
Same therapy was continued and the following drug was added
Dosage form Trade name Generic name strength route Frequency
Inj lasix furosemide 40mg I/v OD
Response to therapy
Very good
Complaints with current therapy
No
29
Case 5
Chief complaints
1 SOB
2 productive cough
3 weight loss
Diagnosis
COPD
30
Tab Pedrol Paracetamol 500mg p/o SOS
Inh salmicort Salmeterol + inh 2 puffs
Fluticasone
propionate
Tab Moxibact Moxifloxicin 400mg p/o 1 tab TDS for
10 days
Response to therapy
Good
NO
31
Case 6
Chief complaints
1 SOB
2 Productive cough
3 High temperatures
4 weaknesses
Diagnosis
COPD
Anaemia
32
Ward level medication
The same therapy was continued and the following drugs were added to therapy
Dosage form Trade name Generic name strength route Frequency
Tab Myrin fort Rifampicin: 150mg, p/o OD
Ethambutol 275mg,
Isoniazid:, 75mg
Pyrazinamide: 400mg
Tab vitab Vitamins - p/o OD
Response to therapy
Satisfactory
33
Comments and recommendations
The potassium level of the patient should properly monitor and if needed
potassium supplements should be given to the patient.
Rifampicin the anti TB drug induce hepatic metabolism of dexamethasone so
its therapeutic effect may be lowered so if needed dose adjustment should be
done.
The physician also has marked the patient as anaemic but his HGB level is
more than the normal which is a sign of emphysema but not of anaemia.
34
Case 7
Chief complaints
1 SOB
2 productive cough from 20 days
3 fever
Diagnosis
COPD
IHD
No
35
Ward level medication
Response to therapy
Good
No
Patient is also suffering from heart disease and is hypertensive so his cardiac activity
should be monitored along with management of COPD because corticosteroids
minimize the effect of antihypertensive drugs so there should be gap between the
administrations of the both drugs or the dose adjustment should be done if this
interaction is very much significant.
36
Case 8
Chief complaints
1 SOB
2 fever
3 irrelevant talking
4 productive cough
5general weakness
PLT 144000mg/dl
Diagnosis
HTN
COPD
Previous medication record for this disease
Dosage form Trade name Generic name strength route Frequency
Tab Ventoline Sulbutamol 4mg p/o BD
Syp Reltus Chlorphiramin,am 2tsf p/o TDS
monium chloride
Tab Orpic Ciprofloxicin 500mg p/o BD
Tab Ramipace Ramipril 2.5mg p/o BD
NO
37
Ward level medication
Response to therapy
Good
38
Comments and recommendations
39
Case 9
Chief complaints
1 productive cough
2 wheezing from last two weeks
3 SOB
4 Fever
Diagnostic tests advised
Test Result Test Result
CXR
Diagnosis
COPD
Diabetes mellitus
Known HTN
NO
40
Ward level medication
The same therapy was continued and the following drugs were added to therapeutic
regimen
Dosage form Trade name Generic name strength route Frequency
Inj Humulin 70/30 Insulin 70/30 Subcutan 30 units
eous morning and
15 at night
Tab Cycin Ciprofloxacin 500mg p/o 1 OD
Same therapy was continued and injection lasix (furosamide) 40mg was given to the
patient in two divided doses of 20 mg each.
Good
Stomach pain
41
Corticosteroids may interact with anti diabetic drugs .corticosteroids have
hyperglycaemic effect
Dexamethasone and furosamide may lead to hypokalemia.[37,38]
Dexamethasone may reduce the effect of antihypertensive drugs.
42
Case: 10
Chief complaints
1productive cough
2 Fever
3 SOB
4 hoarseness of sound
Diagnostic tests advised
Test Result Test Result
HGB 15.2mg/dl RBS 80mg/dl
SGPT 28IU/L S.cr 0.8 mg/dl
ESR 28 mm/hr Sputum AFB negative
CXR
Diagnosis
COPD
URTI
NO
Ward level medication
Dosage form Trade name Generic name strength route Frequency
Inj Astexone Ceftrixone Igm i/v BD
Neb Ventoline Sulbutamol Neb Sos
43
Inj Decodron Dexamethasone 1gm I/v BD
Inh O2 Oxygen - inh Sos
Inj Zantec Ranitidine 50mg I/V BD
Inj neurobion Multivitamins - i/v OD
Inf R/L Ringer lactate 1000ml I/V OD
Inf N/S Normal saline 1000ml I/v Stat
Same therapy was continued and the following drug was added
Inj.....lasix (furasamide)......40mg I/v OD
Response to therapy
Good
Loose motion
Loss of sleep/ insomnia
44
Drug interactions if any
a) Dexamethasone and furosamide may lead to hypokalemia.[ 37,38]
b) Furosamide may potentiate or increase the nephrotoxic effect of cephalosporin
like ceftrixone.[41.42]
c) Ceftrixone and calcium present in ringer lactate solution may form ceftrixone-
calcium crystals which may accumulate in lungs and kidneys of the patient.
d) Sulbutamol and furosamide may also lead to hypokalemia [51]
45
Summarized form of case histories discussed
46
Case 08 A8 68 M kohistan 10-10- SOB HTN Salbo No
Yrs swat 2016 Fever COPD Ciprofloxa Interactions
Irrelevant cin Found
talking Ramipril
Productive Dexa
cough multivitami
n
The statistical data of various drugs used during hospital medication for the discussed
patients is
S.NO Class of drug used for data of 10 patients Quantity %age
1 Bronchodilator 17 22.2%
2 Corticosteroids 14 18.5%
3 Antibiotics 13 17.2%
4 Oxygen therapy 3 3.9%
5 Others 29 38.25%
47
classes of drugs used
bronchodilator
22%
*others
38%
corticosteriod
19%
antibiotics
17%
oxygen
4%
*Other class of drugs includes the drugs which are used for other disease occurred
along with COPD and have no therapeutic role in management of the COPD.
The use of dosage form in the hospital for the discussed patients is summarized for
statistical data as
48
dosage form used
TAB/CAP/SYP
18% INHALER AND
NEBULIZER
26%
PARENTAL
56%
49
Conclusion
I worked for two months in the hospital and interviewed many patients and recorded
their histories. The main objective for the study and project was to know about the
rationale therapy of COPD so keeping in mind that the case histories were evaluated
deeply to check for drug interactions and drug related problems. The possible drug
interactions are discussed in detail at the end of each case.
Smoking is considered to be the most common cause of COPD but the cases
evaluated during this study shows that six patients out of ten were not smokers but
were coal workers and two in ten patients were smokers.
The most notable irrational points of therapy were that, no spirometric tests were
conducted even for a single patient while according to GOLD standards the severity
of the disease is related with the spirometry tests and the choice and strength of drugs
also depends upon that.
The main possibly resulted drug interaction to be occurred was hypokalemia so the
patients potassium level should be monitored carefully during the course of treatment
and potassium supplement in case of need should be prescribed.
It was also found that most of the patients were confirmed or at risk of cardiac
diseases so the use of drugs needed more caution and care.
It was found that some patients were not using the inhaler through proper way and
while inhaled the drugs they expelled the air quickly to dyspnoea so proper dose level
was not achieved.
Poly pharmacy and wrong dose or duplication of dose was also an issue regarding the
rational therapy, some of the patients who already had the drug under another trade
name were taking the same drug again under another trade name prescribed in
hospital, and hence at a time they were using two or more inhalers.
The second main clinically important objective of my project was to know about the
role of clinical pharmacist in healthcare settings so I found intense and immediate
need of the pharmacist who can insure the rationale use of drugs and rationale therapy
of drugs in the hospital. The need of pharmacist to assure rationale therapy was felt in
order to give information to physicians and to patients and to assure rationale therapy.
References
1) Centres for Disease Control and Prevention. Chronic Obstructive Pulmonary
Disease SurveillanceUnited States, 1971-2000. Morbidity and Mortality
Weekly Report. August 2, 2002; 51(SS06):1-16.
4) Wells, Barbara G.; DiPiro, Joseph T.; Schwinghammer, Terry L.; Hamilton,
Cindy. Pharmacotherapy Handbook, 6th Edition 2006 by McGraw-Hill
5) Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung
Health Study participants after 11 years. Am J Respir Crit Care Med 2002;
166(5):675-9.
10) Fletcher CM, Tinker CM, Peto R, Speizer FE. The naturalhistory of chronic
bronchitis and emphysema. Oxford University Press, 1976.
11) Gold DR, Wang X, Wipyj D, Speizer FE, Ware JH, Dockery DW. Effects of
cigarette smoking on lung function in adolescent boys and girls. N Engle J
Med 1996; 335: 931937.
51
12) GOLD pocket guide to COPD diagnosis management and prevention for
health care professionals (pdf) revised edition 2011 page number 8-9.
13) Jemal A. Trends in the leading causes of death in the United States, 1970
2002. JAMA 2005; 294:1255.
14) Buists et al. From the Global Strategy for the Diagnosis, Management and
Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease
(GOLD) 2006.
16) Murray CJL, Lopez AD. Evidence-based health policylessons from the
global burden of disease study. Science 1996; 274:740-743.
17) Longmore JM. Oxford Handbook of Clinical Medicine. 8th ed. Oxford,UK:
Oxford University Press; 2010.
20) Clinical guide lines for management of COPD second edition by ministry of
health Malaysia November 2009 page number 6 available at
www.moh.gov.my
22) Roberts CM, Bugler JR, Melchor R, et al. Value of pulse oximetry in
screening for long term oxygen therapy requirement. European Respiratory
Journal 1993; 6:559-562.
52
25) Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease:
molecular and cellular mechanisms. European Respiratory Journal 2003;
22:672-688.
26) Burgel PR, Nadel JA. Roles of epidermal growth factor receptor activation in
epithelial cell repair and mucin production in airway epithelium. Thorax 2004;
59:992-996.
28) http://ezinearticles.com/?Pathophysiology-of-COPD&id=408861
29) Cranston JM, Crockett AJ, Moss JR, Pegram RW, Stocks NP. Models of
chronic disease management in primary care for patients with mild-to
moderate asthma or COPD: a narrative review. Med J Australia 2008;188(8
Suppl):S50-S52.
31) Poole, P.J. and P.N. Black Mucolytic agents for chronic bronchitis or
chronic obstructive pulmonary University of Auckland, Private Bag 92019,
Auckland, New Zealand
33) Cooper CB. Airflow obstruction and exercise. Resp Med. 2009;103(3):325
34
53
day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest
1994; 105: 14111419.
37) Morris GC, Egan JG, Jones MK "Hypokalaemic paralysis induced by bolus
prednisolone in Graves' disease." Aust N Z J Med 22 (1992): 312
43) Roy AK, Cuda MP, Levine RA "Induction of theophylline toxicity and
inhibition of clearance rates by ranitidine." Am J Med 85 (1988): 525-7
48) Lowe MD, Rowland E, Brown MJ, Grace AA "Beta(2) adrenergic receptors
mediate important electrophysiological effects in human ventricular
myocardium." Heart 86 (2001): 45-51
54
49) Lee KH, Shin JG, Chong WS, Kim S, Lee JS, Jang IJ, Shin SG "Time course
of the changes in prednisolone pharmacokinetics after co-administration or
discontinuation of rifampin." Eur J Clin Pharmacol 45 (1993): 287-9
51) Lipworth BJ, McDevitt DG, Struthers AD "Prior treatment with diuretic
augments the hypokalemic and electrocardiographic effects of inhaled
albuterol." Am J Med 86 (1989): 653-7
52) Book of the title Applied therapeutics 9th edition 2009.
55