3. Drugs Affecting the Respiratory
Bronchodilators
Beta 2 agonists:
Anticholinergics:
Theophylline
Steroids ( inhaled !)
Antileukotriene drugs
BIOLOGIC therapies
Anti-IgE medicine
Anti eosinophilic therapy
4. Bronchodilators
► Bronchodilators are medications used to relieve
breathing problems such as shortness of breath or
wheezing, and the sensation of chest tightness.
They are often prescribed for people suffering from
asthma, chronic obstructive pulmonary disease
(COPD), emphysema or other lung conditions.
6. Beta 2 agonists = β adrenoreceptor agonists
Short- acting SABA
Long- acting LABA
Ultra LABA- allowing for once-daily dosing. They are
considered to be ultra-long-acting β adrenoreceptor agonists
11. β2 adrenergic receptor agonists
a class of drugs that act on the β2 adrenergic
receptor.
they cause:
smooth muscle relaxation - dilation of bronchial
passages,
vasodilation in muscle and liver,
relaxation of uterine muscle,
release of insulin.
13. LABA
►Long acting beta – receptor agonist, are
analogs of albuterol and are long acting
(12 hrs) , more affinity to the beta 2
receptor, has slow onset of action.
► Salmeterol
► Formeterol
14. Why is inhaled formoterol unique
among ß2-agonists?
SABA & LABA
15.
16. Why is inhaled formoterol unique
among ß2-agonists?
Formoterol is the only available long-acting ß2 - agonist
to offer the important benefit of a fast onset of action,
so it can be used for the immediate relief of asthma
symptoms.
Amongst ß2 -agonists, only inhaled formoterol is
suitable for both rescue use and long-term relief in
asthma !!!!!!!!!!!!!!
17. Ultra LABA - have a duration of action of 24 h
►INDACATEROL approved by the EMA in 2009
under the trade name Onbrez Breezhaler. by
the FDA under the trade name Arcapta
Neohaler in 2011
►OLADEROL : 2014 Striverdi Respimat
►VILANTEROL not available by itself but only as a
component of combination drugs:
With fluticasone iGKS: Breo Ellipta (US),
Relvar Ellipta (EU). 2013 as once-daily inhaled
therapy for the treatment of COPD
With umeclidinium - LAMA: Anoro Ellipta.
2013/2014 for the long-term maintenance
treatment of COPD, now in asthma too
18. Indacaterol
► once-daily long-acting beta2 –
adrenergic agonist (LABA)
► Indacaterol may provide an
alternative treatment option in
patients with moderate to severe
chronic obstructive pulmonary disease
(COPD), who may be better suited to a
once-daily dose, compared to the
twice-daily dosing required by other
LABAs. However, this benefit needs to be weighed against a lack of
long-term safety data, a significantly higher cost than twice-daily alternatives
and no evidence supporting improvement in patient orientated outcomes.
22. Anticholinergics are drugs that block the
action of acetylcholine. Acetylcholine is a
neurotransmitter, or a chemical messenger.
It transfers signals between certain cells to
affect how your body functions.
Anticholinergics can treat a variety of
conditions, including:
COPD
Urinary incontinence
Overactive bladder
Parkinson’s disease
certain types of poisoning
23.
24. From atropine and belladonna alkaloids
to „ modern „ inhaled medications for
COPD ( asthma )
26. SAMA: Ipratropium bromide (Atrovent)
- Is a quarternary ammonium derive of atropine that is
given by aerosol. It does not cross Bld-Brain barrier and
is poorly absorb from GIT , thus minimizing Anti-
cholinergic side effects.
-Useful special for patients who cannot tolerate Beta
receptors agonist.
-The effect of this agent starts after 1-2 hours and it is
known to last only from 4 to 6 hours
Combivent – combination of albuterol + ipratropium bromide
Berodual - combination of fenoterol + ipratropium bromide
27. Side effects of inhaled
anticholinergic drugs 1
The most common adverse effect in clinical
trials was dry mouth, which occurred in
16 percent of patients taking ipratropium.
This side effect was considered mild and
typically resolved during the course of
therapy.
Additional side effects included
constipation, blurred vision, glaucoma,
increased heart rate, and urinary
retention.
28. Side effects of inhaled
anticholinergic drugs 2
Anticholinergics are known to cause confusion,
memory loss, and worsening mental function in
people who are older than 65 years increased
risk of dementia.
•
29. LAMA: Tiotropium SPIRIVA
Tiotropium is the first anticholinergic drug
that has been approved for children
and adults with poorly controlled
asthma and is currently considered as an option
for steps 4 and 5 of the Global Initiative for Asthma.
The first for the long-term, once-daily,
maintenance treatment of bronchospasm
associated with COPD
33. 1. Inhibits cAMP phosphodiesterase
which leads to cAMP – smooth muscle
relaxation bronchodilation
xanthine
5’ AMP
Cyclic AMP
phosphodiesterase
Cyclic 3’5
AMP
Mechanism of action
34. Pharmacologic Effects:
Respiratory system
1. Rapid relaxation of bronchial sm. Muscle –
bronchodilation
2.Decrease histamine release
3.Stimulate ciliary transport of mucus
4. Improve respiratory performances by
improving contractility of the diaphragm and
by stimulating the medullary respiratory
center.
35. Pharmacologic Effects:
Effects on other systems
1. Heart : chronotropic and inotropic effect
cardiac stimulation.
2. Pulmonary and peripheral vasodilatation
( B.P)
3. Diuresis
36. Adverse Effects
1. nausea , vomiting and GI bleeding
2. Cardiac arrhythmais
3. Nervousness , seizures , behavioral problems
in children
4. loss of appetite
5. headache, trouble in sleeping, irritability
tremor
37. Pharmacokinetics Theophylline
• rapidly and completely absorb from GIT
metabolize in the liver by oxidation and
demethylation:
Drug and Substance Interactions:
Phenytoin, Allopurinol, The toxic effects of
allopurinol are increased by the simultaneous use of
erythromycin, cimetidine, and fluoroquinolones
Cimetidine
Oral contraceptives
Caffeine,
SSRIs (antidepressants lithium), (barbiturans)
Beta-blockers
Alcohol
40. Theobromine: CAFFEINE:
gentle mild effect
very slow onset
long lasting
50% in bloodstream after 6 to 10 hrs
increases feeling of well being
mild antidepressant
gentle, smooth, sensual stimulation
stimulates cardiovascular system
stimulates muscular system
mild effect on central nervous system
not addictive
no withdrawal symptoms
mild diuretic
stimulates the kidneys
intense strong effect
fast acting
rapid dissipation
50% in bloodstream after 2 to 5 hrs
increases alertness
increases emotional stress
jagged, nervous stimulation
stimulates cardiovascular system
stimulates respiratory system
strong effect on central nervous system
physically addictive
many proven withdrawal symptoms
extreme diuretic
requires large intake of fluids to balance the
diuretic effect
49. Problems with inhaler technique
• Poor asthma control may result from selecting
an inappropriate device or incorrect use of the
right device.
• over 24% of patients made at least one
essential mistake in their inhalation technique.
• Dry powder inhaler devices (DPI) require less
coordination than a pressurised metered dose
inhaler and can improve the delivery of the
drug to the lungs.
56. DEFINITION – the nineties-1993
Asthma is a chronic inflammatory disorder of the
airways.
In susceptible individuals this inflammation causes
reccurent episodes of wheezing,
breathlessness, chest tightness, and cough,
particularly at night and/or in the early morning.
These symptoms are usually associated with
widespread but variable airflow limitation that is
at least partly reversible either spontanously or
with treatment.
The inflammation also causes an associated
increase in airway hyperresponsiveness to a
variety of stimuli.
59. No sleep disruption
No missed school/work
Normal activity levels
No need for ER/hospital visits
Normal (near normal) lung function
Satisfaction with asthma care received
GINA Guidelines:
goals for treatment
61. Why must I use my steroid inhaler
every day even when I am well?
Even when you feel well, the mucus and swelling
continues in the air passages. If you stop using your
steroid inhaler, the air passages in the lungs become
more swollen and produce a lot of sticky mucus.
Therefore you are at risk of having an asthma attack
if you are exposed to the things you are allergic to.
This is because the effect of the steroid inhaler is
slow. It may take up to 4 weeks before it is fully
effective in controlling swelling and reducing mucus
in the air passages.
63. MEDICATIONS for asthma are divided to:
CONTROLLERS
Must be taken daily on
a long-term therapy
and keeping asthma
under control
RELIEVERS
Bronchodilating
medications that act
quickly to relieve
bronchoconstriction
70. Side effects of steroid inhalers :
The dose of inhaled steroid per day is a lot smaller
and the side effects are less frequent and less
severe than steroid tablets.
For example, 2 puffs of Pulmicort inhaler (200
micrograms) a day delivers 400 micrograms of
inhaled steroid. In acute asthma attack, six 5
milligrams of steroid tablets a day will be given-
30,000 micrograms , 75 times more than inhaled
steroid.
74. Side effects of systemic
steroid :
• short course
• long- term therapy
75. Rescue steroids tablets
Short courses of steroid tablets, also called
rescue steroids, are necessary to treat
acute asthma attacks. They are usually
prescribed for 1 to 2 weeks
During an asthma attack, steroid tablets
are given to quickly control swelling and
reduce mucus in the air passages to
prevent severe asthma attack.
76. Side effects of steroid tablets:
Only a very small number of people with
troublesome asthma symptoms, who need to
take long- term steroids tablets over months
or years, will have serious side effects. These
include osteoporosis, high blood pressure,
cataract, weight gain, bruising and prone to
infection. There is a much greater risk of side
effects when taken small doses of steroid tablets
over a long period than high doses for 1- 2
weeks.
83. Side effects of steroid inhalers :
Side effects are uncommon, mild and
temporary.
Possible side effects are:
hoarse voice ,
throat irritation,
fungay infection.
You can avoid by rinsing your throat well
after inhaling the medicine.
85. MEDICATIONS
for asthma are divided to:
CONTROLLERS
Must be taken daily on
a long-term therapy
and keeping asthma
under control
RELIEVERS
Bronchodilating
medications that act
quickly to relieve
bronchoconstriction
92. INTERACTIONS BETWEEN CORTICOSTEROIDS
AND ß2-AGONISTS
Glucocorticoid
receptor
ß2-Adrenoceptor
• Effect of corticosteroids on ß2-adrenoceptors
Corticosteroid
Anti-inflammatory effect
• Effect of ß2-agonists on glucocorticoid receptors
ß2-Agonist
Bronchodilatation
Barnes Nice 2001
Other
combinations
than with
budesonide
93.
94.
95.
96.
97.
98.
99.
100.
101.
102. Alvesco® (ciclesonide)
•a new generation inhaled corticosteroid
(ICS) for the treatment of persistent
asthma
•Alvesco® is a once-daily treatment for
most patients and is unique because it
activates on-site in the lungs with little
activation in the mouth and throat.
•Patients using Alvesco® in clinical
studies experienced an oral side-effect
profile (oral thrush, hoarseness of voice)
similar to that of placebo
106. leukotriene inhibitors
These medications block the effects of
leukotrienes, immune system chemicals that
cause asthma symptoms. Leukotriene
modifiers can help prevent symptoms for up
to 24 hours. Examples include:
Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (Zyflo)
107. What side effects may occur?
More common side
effects may include:
•Headache
•diarrhea
•nausea
Montelukast or Singulair is
generally well tolerated.
108. Leukotriene modifiers
In rare cases, montelukast is linked to
psychological reactions, such as agitation,
aggression, hallucinations, depression and
suicidal thinking.
109. What conditions or indications might
treat with leukotriene inhibitors?
Allergic Rhinitis and asthma
Aspirin induced asthma
EOSINOPHILIC RHINITIS AND ASTHMA
110. Asthma phenotypes: the evolution from
clinical to molecular approaches
BIOLOGICAL TREATMENT
121. Are there any side effects or
adverse reactions to Xolair?
Common side effects of Xolair include a
reaction at the injection site, viral
infections, upper respiratory tract infection,
sinusitis, headache and sore throat.
Several rare, yet severe side effects were
reported in the original studies. They
include malignancy and anaphylaxis
127. Global Initiative for Chronic
Obstructive Lung Disease
In collaboration with:
National Heart, Lung, and
Blood Institute, NIH
and
World Health Organization
130. Percent Change in Age-Adjusted
Death Rates, U.S., 1965-1998
0
0.5
1.0
1.5
2.0
2.5
3.0
Proportion of 1965 Rate
0.0
0.5
1.0
1.5
2.0
2.5
3.0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
–59% –64% –35% +163% –7%
Coronary
Heart
Disease
Stroke Other CVD COPD All Other
Causes
Source: NHLBI/NIH/DHHS
131. Of the six
leading causes
of death in the
United States,
only COPD has
been increasing
steadily since
1970
Source: Jemal A. et al. JAMA 2005
132. Risk Factors for COPD
Nutrition
Infections
Socio-economic
status
Aging Populations
133. Definition of COPD
COPD is a preventable and treatable disease with
some significant extrapulmonary effects that may
contribute to the severity in individual patients.
Its pulmonary component is characterized by airflow
limitation that is not fully reversible.
The airflow limitation is usually progressive and
associated with an abnormal inflammatory response
of the lung to noxious particles or gases.
151. The Immunomodulatory
Effects of Macrolides
decrease in the number of neutrophils, and
the concentrations of neutrophil elastase,
IL-8, IL-6, IL-1,TNF-alpha, eosinophilic
cationic protein, and matrix
metalloproteinase 9. Inhibition of neutrophil function was reported
more frequently than eosinophil function
decrease in Th 2 cells, cytokines: IL-4, IL-5,
IL-6 was reported more frequently than a
decrease in Th1 cytokines :IL-2, INF-
gamma.
152.
153. Causes of Airflow Limitation
Irreversible
Fibrosis and narrowing of the
airways
Loss of elastic recoil due to
alveolar destruction
Destruction of alveolar support
that maintains patency of
small airways
154. Causes of Airflow Limitation
Reversible
Accumulation of inflammatory
cells, mucus, and plasma
exudate in bronchi
Smooth muscle contraction in
peripheral and central airways
Dynamic hyperinflation during
exercise
155. Objectives of COPD
Management
Prevent disease progression
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat exacerbations
Prevent and treat complications
Reduce mortality
Minimize side effects from treatment
156. Manage Stable COPD
None of the existing medications for COPD
has been shown to modify the long-term
decline in lung function that is the hallmark
of this disease .
Therefore, pharmacotherapy for COPD is
used to decrease symptoms and/or
complications.
157. IV: Very Severe
III: Severe
II: Moderate
I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70%
FEV1 > 80%
predicted
FEV1/FVC < 70%
50% < FEV1 < 80%
predicted
FEV1/FVC < 70%
30% < FEV1 <
50% predicted
FEV1/FVC < 70%
FEV1 < 30%
predicted
or FEV1 < 50%
predicted plus
chronic respiratory
failure
Add regular treatment with one or more long-acting
bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add long term
oxygen if chronic
respiratory failure.
Consider surgical
treatments
158. Management of Stable COPD
Other Pharmacologic Treatments
Mucolytic agents, Antitussives:
Not recommended in stable COPD !!!!!!!!!!
VACCINATION : YES !!!!!!!!
Influenza Vaccine. Individuals with COPD should receive the annual flu
vaccination.Flu season typically lasts from October to May, peaking from
December to February. However, the flu can be transmitted at any time during
the year.
Pneumococcal Vaccine. PCV13 and PPSV23, are recommended for all
adults 65 years or older, particularly those with chronic lung conditions like
COPD. They are also specifically recommended for younger individuals with
COPD. These vaccines provide protection against various pneumococcal
bacteria that can cause pneumonia, among other conditions.
159. Management of Stable COPD
Non-Pharmacologic Treatments
Rehabilitation: All COPD patients benefit from
exercise training programs, improving with
respect to both exercise tolerance and
symptoms of dyspnea and fatigue
Oxygen Therapy: The long-term administration
of oxygen (> 15 hours per day) to patients with
chronic respiratory failure has been shown to
increase survival .
160. Manage Stable COPD
Bronchodilator medications are central to the
symptomatic management of COPD . They are
given on an as-needed basis or on a regular
basis to prevent or reduce symptoms.
The principal bronchodilator treatments are Beta2-
agonists, anticholinergics, theophylline, and a
combination of these drugs .
161. Manage Stable COPD
Regular treatment with inhaled glucocortico-
steroids should only !!!! be prescribed for
symptomatic COPD patients with an FEV1
< 50% predicted and repeated
exacerbations requiring treatment with
antibiotics and/or oral glucocorticosteroids
162. Manage Stable COPD
The long-term administration of oxygen
(> 15 hours per day) to patients with
chronic respiratory failure has been
shown to increase survival .
163. Manage Exacerbations
The most common causes of an
exacerbation are infection of the
tracheobronchial tree and air pollution
164. Manage Exacerbations
Patients experiencing COPD
exacerbations with clinical signs of
airway infection (e.g., increased
volume and change of color of
sputum, and/or fever) may benefit
from antibiotic treatment
165.
166.
167. Oxygen
Oxygen is a powerful symbol of medical care that
is probably more important than its actual
therapeutic value in the relief of breathlessness.
It is widely available and commonly prescribed
by medical and paramedical staff but is often
given without careful evaluation of its potential
benefits and side effects. Like any drug therapy
there must be clear indications for treatment with
oxygen, appropriate prescription, vigilant
monitoring and appropriate methods of delivery.
168. Definitions - Hypoxaemia
The following laboratory values, obtained
while breathing ambient air:
Arterial partial pressure of oxygen (PaO2)
£55 mm Hg
Arterial oxygen saturation (SaO2) £88%
In the presence of secondary
polycythaemia and pulmonary
hypertension:
PaO2 between 55-60mm Hg
169. Long Term Oxygen Therapy
(LTOT)
Provision of oxygen therapy for continuous
use at home for patients with chronic
hypoxaemia. The flow rate must be
sufficient to raise the waking oxygen
tension in adults to above 60mm Hg.
It is nighttime
170. In the literature Long Term
Oxygen Therapy
Is often used as a synonymous of:
Continuous Oxygen Therapy (COT)
Home Oxygen Therapy (HOT)
171. Home oxygen therapy
Home oxygen therapy is an effective but
potentially expensive and inconvenient
intervention. It should be prescribed only
for patients in whom there is evidence of
benefit, such as those whose disability
relates to a chronic reduced arterial
oxygen concentration (chronic
hypoxaemia).
174. 1. Oxygen concentrators
Electrically powered
Uses molecular sieve beds to
filter and concentrate oxygen
molecules from ambient air,
generating oxygen
concentrations of 90% to 98%
Maximum flow of 3-5 L/min
Backup oxygen supply with a
cylinder is necessary
175. 2. Compressed gas cylinders
H-sizedLarge and
heavy (about 150lbs)
Provides oxygen for
about 57 hours at flow
of 2 L/min
176. 3. Liquid oxygen reservoirs
Can be used to refill
portable units
Last 5-7 days at 2 L/min
Relatively high cost /
occasional “freezing” of
the valve at flow of about
8 L/min / evaporation of
the liquid oxygen when
not in use.
177. Asthma,COPD and SARS-CoV-2
No evidence of a beneficial effect of regular
ICS use among people with COPD and
asthma on COVID-19-related mortality.
Results of studies do not support any
change to the current clinical guidelines for
the routine treatment of people with COPD
or asthma with ICS during outbreaks of
SARS-CoV-2 infection.
178. Asthma,COPD and SARS-CoV-2
A new study found no benefit of inhaled
corticosteroid use in protecting against
COVID-19-related mortality in patients with
asthma and COPD.
179. Asthma,COPD and SARS-CoV-2
Use of inhaled ICS protects against COVID-
19 is still unknown, but to dismiss this
hypothesis as nonsense is premature. ICS
as a therapeutic intervention still need to
studied and clinical trials assessing their
efficacy in COVID-19 are ongoing in
various clinical settings, the results of
which are eagerly awaited.
180. August 2021 Lancet
Are Inhaled Steroids Effective
for Treating Patients with
COVID-19?
David J.Amrol MD
181. This study was limited by lack of a placebo
control, poor follow-up, and failure to find a
significant difference in the most important
endpoint of fewer hospitalizations and
deaths. However, it suggests that older
patients and those with comorbidities
might benefit from ICS if they have mild
COVID-19. Monoclonal antibody treatment
is preferable but ICS is a simple and
inexpensive option with little apparent
downside, and offering it to select higher-
risk patients (similar to those in this trial)
would be reasonable.
182. The Lancet
September 2021,
Inhaled budesonide for COVID-19 in people
at high risk of complications in the
community in the UK (PRINCIPLE): a
randomised, controlled, open-label,
adaptive platform trial
183. Inhaled budesonide improves time to
recovery, with a chance of also reducing
hospital admissions or deaths (although
our results did not meet the superiority
threshold), in people with COVID-19 in the
community who are at higher risk of
complications.
