Respiratory Drugs

PCOL2605

Presented by: Dr Brent McParland (PhD)

Discipline of Pharmacology
brent.mcparland@sydney.edu.au
CPC 2nd Floor

The University of Sydney Page 1

Created by Peter Carroll, adapted by Brent McParland
 Learning Objectives

– Explain the basic pathophysiology

and triggers of asthma
– Discuss the mechanism of action,
and adverse effects of drugs used
in the treatment of asthma https://onlinedoctor.lloydspharmacy.co
m/uk/info/correct-inhaler-use
including
- short acting β2 receptor agonists
- long acting β2 receptor agonists
- corticosteroids
- M3 receptor antagonists www.healthywa.wa.gov.au

- leukotriene receptor antagonists

The University of Sydney Page 2
 Learning Objectives

– Explain the benefits of an

Asthma Action
(Management) Plan
– Understand the basic
pathology of chronic
obstructive pulmonary
disease http://www.webmd.com/lung/copd/ss/slidesho
w-treating

– Discuss the treatment options for chronic

obstructive pulmonary disease

The University of Sydney Page 3

 Asthma
– Asthma is a chronic, inflammatory airways disease
– The pathophysiology of asthma is complex and
involves many mediators including histamine,
interleukins and leukotrienes
– The process also involves eosinophils, macrophages,
neutrophils, T lymphocytes, mast cells and
immunoglobulin type E (IgE)

Border M et al. Pharmacology for Pharmacy and the Health Sciences, Chapter 11, Oxford University Press, 2010
Rang and Dale’s Pharmacology Chapter 28, 8th Edition
The University of Sydney Page 4
 Asthma
– Asthma is characterised by
- reversible bronchoconstriction

- inflammation of the airways

- mucous secretion

- hyper-reactive airways
- cough

Border M et al. Pharmacology for Pharmacy and the Health Sciences, Chapter 11, Oxford
University Press, 2010
The University of Sydney Rang and Dale’s Pharmacology Chapter 28, 8th Edition Page 5
 Asthma
– Inflammation results in
contraction of the smooth
muscle of the airways,
swelling of the airway wall
and mucous secretion http://vector.childrenshospital.org/2013/12/the-obesity-asthma-
connection-a-link-in-the-innate-immune-system/

– Patients experience
- wheezing
- shortness of breath
- chest tightness
- cough
- dyspnoea
http://www.azsneeze.com/unlock-the-mystery-of-asthma/
Border M et al. Pharmacology for Pharmacy and the Health Sciences, Chapter 11, Oxford University Press, 2010
The University of Sydney Rang and Dale’s Pharmacology Chapter 28, 8th Edition Page 6
 Asthma
– It is estimated that in Australia between 10-12% of adults
and between 10-15% of children have asthma
– Involves both genetic and environmental factors
– In 2014 asthma caused the deaths of 419 Australians (in
1989 it caused 964 deaths)

http://www.aihw.gov.au/asthma/; Gowan J and Roller L (2011). Australian Journal of Pharmacy, 92, 49-54
http://www.aihw.gov.au/asthma/deaths/; https://www.nationalasthma.org.au/living-with-
The University of Sydney Page 7
asthma/resources/health-professionals/reports-and-statistics/asthma-mortality-statistics
 Asthma
– Triggers for asthma include
- bacterial and viral respiratory tract infections
- allergens including pollens, moulds, cats, house dust
mites, eggs, shellfish, nuts
- occupational exposure e.g. latex, wood dust
- tobacco smoke and some food additives e.g.
monosodium glutamate, tartrazine
- exercise, cold air, emotional stress
- some medications e.g. beta blockers, NSAIDS (not all
patients)

Border M et al. Pharmacology for Pharmacy and the Health Sciences, Chapter 11, Oxford University Press, 2010
The University of Sydney Gowan J and Roller L (2011). Australian Journal of Pharmacy, 92, 49-54 Page 8
 Asthma

– Over 80% of patients

who suffer from asthma
also suffer from
allergic rhinitis (hay
fever)
– Up to 40% of patients
who suffer from
allergic rhinitis also
suffer from asthma
– Atopic individuals

The University of Sydney World Allergy Week, 2015. http://www.slideshare.net/ivancev/waw2015slides-final Page 9

 Innervation of Human Airways
– The parasympathetic nervous system innervates bronchiole
smooth
– Postganglionic parasympathetic nerve fibres release
acetylcholine which acts on M3 receptors to produce
bronchoconstriction and mucous secretion
– The sympathetic nervous system does not innervate
bronchiole smooth muscle
– However, β2 receptors are present on bronchiole smooth
muscle, have constitutive activity and activated by Adrcirc
– Stimulation of these β2 receptors produces bronchodilation,
reduced mast cell release of mediators and increased
mucociliary clearance

The University of Sydney Page 10

Rang and Dale’s Pharmacology Chapter 28, 8th Edition
 Questions

– What are the main cells involved in the pathophysiology of

asthma?
– What binds to FCR1?
– What is meant by hyper-reactive airways?
– What percent of people have asthma and is it greater or less
for children?
– Name some triggers of asthma?
– What is the relationship between allergic rhinitis and asthma?
– Describe the autonomic control of airway smooth muscle?
– What is the significance of β2 adrenoceptors having constitutive
activity?
– How does the autonomic nervous system activate β2
adrenoceptors?

The University of Sydney Page 11

 Pharmacological Treatment of Asthma

– Short acting β2 receptor agonists e.g. salbutamol

– Long acting β2 receptor agonists e.g. salmeterol
– Corticosteroids e.g. fluticasone
– M3 receptor antagonists e.g. ipratropium
– Leukotriene receptor antagonists e.g. montelukast
– Cromones e.g. sodium cromoglycate

The University of Sydney eMIMS Product Information, April 2016 Page 12

 Short Acting β2 Receptor Agonists

– Examples include salbutamol and terbutaline

– They are used to provide rapid relief of
asthma symptoms
– They have a rapid onset of action (5-10
minutes) and a short duration of action (3-6
hours)
– They are referred to as reliever medications

The University of Sydney eMIMS Product Information, April 2016 Page 13

 Short Acting β2 Receptor Agonists

– Stimulate β2 receptors on bronchiole smooth muscle

and produce bronchodilation
– They may also inhibit mediator release e.g. from
mast cells, and increase mucus clearance by an
action on cilia
– When taken prior to exercise they are also used to
prevent exercise induced asthma
– They should not be used on a regular basis, and the
need to increase their use to control symptoms
indicates a deterioration of asthma control
Therapeutic Guidelines, Respiratory
The University of Sydney eMIMS Product Information, April 2016 Page 14
 Short Acting β2 Receptor Agonists

– They are generally

administered directly into
the lungs by pressurised
metered dose inhalers
(puffers) or by breath
activated devices
– Check patient technique
– Can be given by nebuliser,
and orally

The University of Sydney eMIMS Product Information, April 2016; http://www.clubwarehouse.com.au/505685 Page 15
 Short Acting β2 Receptor Agonists

– Adverse effects of β2 agonists may include

- tremor (of the hands)
- nervousness and tenseness
- hypokalaemia
- tachycardia and palpitations (stimulation of β1 receptors
in the heart may also occur as the selectivity of β2
agonists for β2 receptors is not absolute)
- hyperactivity in children

The University of Sydney eMIMS Product Information, April 2016 Page 16

 Long Acting β2 Receptor Agonists (LABAs)

– Examples include eformoterol and salmeterol

– Eformoterol has rapid onset of action (within
minutes) and a long duration of action (12 hours)
– Salmeterol has an onset of action around 10-30
minutes and a long duration of action (12 hours)
– Stimulate β2 receptors on bronchiole smooth muscle
and produce bronchodilation
– They may also inhibit mediator release e.g. from
mast cells, and increase mucus clearance by an
action on cilia
The University of Sydney eMIMS Product Information, April 2016 Page 17
 Long Acting β2 Receptor Agonists (LABAs)
– Their longer duration of action is thought to be
due to the fact that they are more lipid soluble
than the short acting β2 agonists
– They should not be used as monotherapy
- uncontrolled airway inflammation
- increased risk of asthma attack/death
– Use long acting β2 agonists in combination with a
corticosteroid
– They have a similar side effect profile to the short
acting β2 agonists
Therapeutic Guidelines, Respiratory
The University of Sydney Page 18
eMIMS Product Information, April 2016
 Corticosteroids
– Corticosteroids are the cornerstone treatment for patients
with chronic asthma
– They exert an anti-inflammatory effect on the airways and
reduce airway hyper-reactivity
– They are the first line therapy for achieving and maintaining
symptom control
– They are not direct acting bronchodilators
– They are used prophylactically to reduce the
incidence and severity of asthma symptoms and
attacks
– They mimic endogenous cortisol (adrenal cortex),
but with minimal mineralocorticoid activity
(aldosterone)
The University of Sydney eMIMS Product Information, April 2016 Page 19

https://www.integrativepro.com/Resources/Integrative-Blog/2016/The-HPA-Axis
 Corticosteroids

– They are used on a continual basis even though a

patient’s asthma is well controlled
– A patient’s asthma is well controlled because of
the use of the corticosteroids
– They are referred to as preventer medications
– Examples of those given by inhalation include
beclomethasone, budesonide, ciclesonide and
fluticasone
– Examples of those given orally include
prednisone and prednisolone
The University of Sydney eMIMS Product Information, April 2016 Page 20
 Corticosteroids

– Inhaled corticosteroids should be used in the lowest

possible dose as systemic side effects may occur
even though the medication has been delivered
directly into the lung
– A long acting β2 receptor agonist may be added
if good asthma control has not been achieved
– The combined use with a β2 receptor agonist may
allow the dose of the corticosteroid to be reduced

The University of Sydney Therapeutic Guidelines, Respiratory Page 21

eMIMS Product Information, April 2016
 Corticosteroids
– Adverse effects of inhaled corticosteroids may
include
- oropharyngeal candidiasis (thrush) and hoarseness which
may be reduced or eliminated by advising patients to
rinse their mouth out with water after each inhalation
- reduced bone mineral density and osteoporosis
- cataracts and glaucoma (rare)
- retardation of growth in children and adolescents
(children catch up with no long term effects)

The University of Sydney eMIMS Product Information, April 2016 Page 22

 Questions
– What are the main drugs used for the treatment of asthma?
– What is the onset of action and ~t1/2 for salbutamol?
– What are other actions of β2 adrenoceptor agonists ?
– What are some common side effects of β2 adrenoceptor agonists?
– What should β2 adrenoceptor agonists not be used for?
– What is the main difference between salbutamol and salmeterol?
– What is the main difference between eformoterol and salmeterol?
– Can LAβAs be used for monotherapy?
– What is the main difference between bronchodilators and
corticosteroids and with the later explain its therapeutic role?
– What do corticosteroids mimic and what is the major difference
between them and what is released from the adrenal cortex?
– What is the main route of administration for corticosteroids?
– Can you name some corticosteroids?
– What is prendnisolone used for?
– How quickly do corticosteroids work and why might this be an issue
with respect to adherence?
– Can you name some side effects with corticosteroid treatment?
The University of Sydney Page 23
 M3 Receptor Antagonists
– Referred to as anticholinergics (antimuscarinics)
– They competitively inhibit M3 muscarinic receptors
on bronchiole smooth muscle and produce
bronchodilation
– Examples include ipratropium and tiotropium
– They are inhaled and are mainly used in the
treatment of chronic obstructive pulmonary disease
(COPD), although ipratropium is used in the
treatment of asthma
– May produce anticholinergic (antimuscarinic) side
effect e.g. dry mouth, blurred vision
The University of Sydney eMIMS Product Information, April 2016 Page 24
 Leukotriene Receptor Antagonists

– The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are

potent inflammatory mediators released from
various cells including mast cells and eosinophils
– In asthma cysteinyl leukotrienes can produce
bronchoconstriction, mucous secretion, increased
vascular permeability and eosinophil recruitment
– Montelukast is a leukotriene receptor antagonist
which inhibits cysteinyl leukotriene receptors in the
airways and produces bronchodilation

The University of Sydney eMIMS Product Information, April 2016 Page 25

 Leukotriene Receptor Antagonists
– Montelukast is used primarily in children
– It may also be of benefit in the treatment of those
patients who suffer from aspirin (NSAID) induced
asthma
– It is taken orally
– Adverse effects include
- abdominal pain and headache
- aggressive behaviour, anxiousness, depression (suicidal
tendencies, disorientation, disturbance in attention,
dream abnormalities, hallucinations, insomnia and
memory impairment

The University of Sydney eMIMS Product Information, April 2016 Page 26

 Cromones
– Examples include sodium cromoglycate and nedocromil
sodium
– Inhibit the release of inflammatory mediators from
mast cells
– They are used in the prophylactic treatment of
bronchial asthma, including the prevention of exercise
induced bronchospasm
– Administered by inhalation
– Generally less effective than corticosteroids and are
not widely used

The University of Sydney eMIMS Product Information, April 2016 Page 27

inPharmation, Optimising asthma management 12(5), June 2011
 Asthma Management
– Patients taking preventer/prophylactic therapy e.g.
corticosteroids to control their asthma should have access
to reliever medication in case they experience asthma
symptoms
– Rapid onset short acting β2 receptor agonist e.g.
salbutamol or terbutaline
– Rapid onset long acting β2 receptor agonist e.g.
eformoterol (only available in combination with a
corticosteroid - regular maintenance treatment and as
needed in response to symptoms)
– Symbicort Maintenance and Reliever Therapy (SMART)

The University of Sydney Page 28

 Asthma Action Plan

– The aim of an asthma action plan is to help the person with

asthma and/or their carer to take early action to prevent or
reduce the severity of an asthma attack

– An asthma action plan helps the person with asthma and/or

their carer to recognise worsening asthma, and gives clear
instructions on what to do if this happens

https://www.nationalasthma.org.au/health-professionals/asthma-action-plans
The University of Sydney Page 29
 Asthma Plan

Asthma Buddy smartphone app

The University of Sydney
https://www.nationalasthma.org.au/living-with-asthma/asthma-action-plans/asthma-action-plan-examples Page 30
https://www.nps.org.au/australian-prescriber/articles/rational-prescribing-for-asthma-in-adults-written-asthma-action-plans
 Chronic Obstructive Pulmonary Disease (COPD)

– Chronic obstructive pulmonary disease (COPD) is an

umbrella term for a number of serious, progressive and
disabling lung diseases that prevent proper breathing
– COPD is associated with inflammatory responses within
the lungs and includes emphysema (shortness of breath)
and chronic bronchitis (cough and sputum)
– In 2013 COPD was the fifth leading cause of death in
Australia

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/lung-conditions-chronic-
obstructive-pulmonary-disease-copd
eTG Respiratory
The University of Sydney Page 31
http://www.asthmahandbook.org.au/clinical-issues/copd
– In the lungs the alveoli
are the sites of gas
exchange (O2 and CO2)
between the inspired air
and the blood
– Each lung contains
approximately 150
million alveoli

http://millbasindoctor.com/copd-chronic-
obstructive-pulmonary-disease/
The University of Sydney http://www.nhlbi.nih.gov/health/health-topics/topics/copd
Page 32
 Chronic Obstructive Pulmonary Disease (COPD)

– The major cause of COPD is cigarette smoking

– Symptoms of COPD include
- breathlessness - fatigue
- cough - wheezing
- sputum production - cyanosis
- respiratory tract infections

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/lung-
The University of Sydney conditions-chronic-obstructive-pulmonary-disease-copd Page 33
eTG Respiratory; http://www.asthmahandbook.org.au/clinical-issues/copd
 Chronic Obstructive Pulmonary Disease (COPD)

– Treatment options include

- smoking cessation
- short acting β2 receptor agonists
- Long & ultra-long acting β2 receptor agonists
- M3 receptor antagonists
- corticosteroids
- influenza and pneumococcal vaccination

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/lung-conditions-
chronic-obstructive-pulmonary-disease-copd
The University of Sydney eTG Respiratory; http://www.asthmahandbook.org.au/clinical-issues/copd Page 34
The University of Sydney Page 35