Download The role of medicine in respiratory diseases

The role of medicine in
respiratory diseases management
Eti Nurwening Sholikhah
Department of Pharmacology and Therapy
Faculty of Medicine
Universitas Gadjah Mada
Yogyakarta
• The respiratory system is subject to
many disorders that interfere with
respiration and other lung functions,
including
– Respiratory tract infections
– Allergic disorders
– Inflammatory disorders
– Conditions that obstruct airflow (e.g.
asthma and chronic obstructive pulmonary
disease, COPD)
2
Learning Objectives
The students understand the drugs that act
on the respiratory system include
– Bronchodilators
– Corticosteroids
– Cromoglycates
– Leukotriene receptor antagonists
– Antihistamines
– Cough preparations
– Nasal decongestants
3
Bronchodilators
• Drugs used to relieve bronchospasms
associated with respiratory disorders
• Includes:
– Adrenoceptor agonists
• Selective β2-agonists & other adrenoceptor agonists
– Antimuscarinic bronchodilators
– Xanthine derivatives
9
• Adrenoceptor agonists
– (i) Selective beta2 agonists
• Stimulate beta2 receptors in smooth muscle of the lung,
promoting bronchodilation, and thereby relieving
bronchospasms
• They are divided into short-acting & long acting types
10
Short-acting β-2 agonists
Drug
Salbutamol
Terbutaline
Formulation
Dosage
Adult
Child
Oral tablet (C.R)
8 mg twice daily
4 mg twice daily
Inhaler (MDI), 100mcg/dose
100-200mcg up to three to
four times daily
Same as adult
Syrup, 2mg/5ml
4 mg three to four times
daily
1-2 mg three to four times
daily (≥2 yr)
Oral tablet (S.R)
5-7.5 mg two times daily
-
Inhaler 500mg / dose
( Turbuhaler)
500 mcg up to four times
daily
-
Inhaler 250mg / dose (MDI)
250-500mcg up to 3-4 times
daily
Same as adult
11
Long-acting β-2 agonists
Drug
Formoterol
Formulation
Inhaler 4.5mcg / dose
(Turbuhaer)
Dosage
Adult
Child
4.5-9 mcg once or twice
daily
Same as adult
50-100 mcg twice daily
Same as adult
Inhaler 9mcg / dose
(Turbuhaer)
Salmeterol
Inhaler 25mcg / dose
(MDI)
50 mcg / dose (Accuhaler) 50 mcg twice
Same as adult
12
• Adverse effects
– Tachycardia and palpitations
– Headache
– Tremor
13
– (ii) Other adrenoceptor agonists
• Less suitable & less safe for use as bronchodilators
because they are more likely to cause arrhythmias &
other side effects
– Ephedrine
» Adults: 15-60 mg tid po
» Child: 7.5-30 mg tid po
• Adrenaline (epinephrine) injection is used in the
emergency treatment of acute allergic and anaphylactic
reactions
14
• Antimuscarinic bronchodilators
– Blocks the action of acetylcholine in bronchial
smooth muscle, this reduces intracellular GMP, a
bronchoconstrictive substance
– Used for maintenance therapy of
bronchoconstriction associated with chronic
bronchitis & emphysema
15
Drug
Formulation
Dosage
Adult
Child
Ipratropium
Inhaler 20 mcg /
dose (MDI)
20-80 mcg three
to four times a
day
20-40 mcg three
to four times a
day (≥6yrs)
Tiotropium
Inhaler 18 mcg
/dose
18 mcg daily
Not
recommended in
children and
adolescents
• Adverse effects:
– Dry mouth
– Nausea
– Constipation
– Headache
17
• Xanthine Derivatives
– Main xanthine used clinically is theophylline
– Theophylline is a bronchodilator which relaxes
smooth muscle of the bronchi, it is used for
reversible airway obstruction
– One proposed mechanism of action is that it acts
by inhibiting phosphodiesterase, thereby
increasing cAMP, leading to bronchodialtion
18
Drug
Formulation
Dosage
Adult
Theophylline
Aminophylline
Child
Tablet 200 / 300 200 – 300 mg twice
mg (S.R.)
daily
10 mg / kg ((≥2yrs) twice
daily
Capsule 50 /
100 mg (Slow
release)
7-12 mg/ kg / day in
two divided doses
10-16 mg / kg / day in two
divided doses (9–16yrs)
13-20 mg / kg / day in two
divided doses (30
months – 8 yrs)
Syrup 80 mg /
15 ml
25 ml q6h
1 ml / kg (Max 25 ml) q6h
(≥2yrs)
Injection 25 mg
/ ml
10 ml
500 mcg / kg / hr IV
infusion, adjust when
necessary
1 mg / kg /hr (6 months –
9 years)
800 mcg / kg /hr (10 – 16
yrs)
IV infusion, adjust when
necessary
19
– Adverse effects:
• Toxicity is related to theophyline levels (usually 5-15 µg/ml)
• 20-25 µg/ml : Nausea, vomiting, diarrhea, insomnia,
restlessness
• >30 µg/ml : Serious adverse effects including dysrhythmias,
convulsions, cardiovascular collapse which may result in
death
20
METHYLXANTHINES POSSIBLE ACTIONS
1. Relaxation of smooth muscle, particularly bronchial
smooth muscle
2. Stimulate the central nervous system
3. Weakly positive chronotropes and inotropes
4. Mild diuretics.
Corticosteroids
• Used for prophylaxis of chronic asthma
• Suppressing inflammation
– Decrease synthesis & release of inflammatory
mediators
– Decrease infiltration & activity of inflammatory cells
– Decrease edema of the airway mucosa
• Decrease airway mucus production
• Increase the number of bronchial beta2 receptors &
their responsiveness to beta2 agonists
22
Drug
Formulation
Dosage
Adult
Beclometha
sone
Child
Inhaler 50 mcg /
dose
(MDI)
200 mcg twice daily 50 – 100 mcg two
/ 100mcg three to
to four times daily
fours times daily
Up to 800 mcg daily
Inhaler 250 mcg /
dose
(MDI)
500 mcg twice daily Not recommended
/ 250 mcg four
times daily
23
Drug (Cont’d)
Budesonide
Formulation
Inhaler 50 mcg / dose
(MDI)
Dosage
Adult
Child
200 mcg twice daily
Up to 1.6 mg daily
50 – 400 mcg twice
daily
Up to 800 mcg daily
200-800 mcg once daily
in evening
Up to 1.6 mg daily in
two divided doses
200-800 mcg daily in
two divided doses /
200-400 mcg once
daily in evening
(<12 yrs)
Inhaler 200mcg / dose
(MDI)
Inhaler 100 mcg / dose
(Turbuhaler)
Inhaler 200 mcg / dose
(Turbuhaler)
Inhaler 400 mcg / dose
(Turbuhaler)
24
Drug (Cont’d) Formulation
Fluticasone
Inhaler 25mcg / dose (MDI)
Inhaler 50 mcg / dose (MDI)
Inhaler 125 mcg / dose (MDI)
Dosage
Adult
Child
100 – 1000
mcg twice
daily
50-100 mcg twice
daily (4-16 yrs)
Inhaler 250 mcg / dose (MDI)
Inhaler 50 mcg / dose
(Accuhaler)
Inhaler 100 mcg / dose
(Accuhaler)
Inhaler 250 mcg / dose
(Accuhaler)
Acute attacks of asthma should be treated with short courses of
oral corticosteroids, starting with a high dose for a few days 25
• Adverse effects
– Inhaled corticosteroids:
•
•
•
•
Candidiasis of the mouth or throat
Hoarseness
Can slow growth in children
Adrenal suppression may occur in long-term, high dose
therapy
• Increases the risk of cataracts
26
Cromoglycates
• Stabilise mast cells & prevent the release of
bronchoconstrictive & inflammatory
substances when mast cells are confronted
with allergens & other stimuli
• Only for prophylaxis of acute asthma attacks
27
Drug
Formulatio Dosage
n
Adult
Cromoglycate
Na
Nedocromil
Sodium
Child
Inhaler (1
mg &
5mg/dose)
10 mg four times daily,
Same as adult
may be increased to six to
eight times daily
Nebuliser
solution 10
mg / ml 2
ml
20 mg four times daily,
may be increased six
times daily
Same as adult
Inhaler 2
mg / dose
(MDI)
4 mg two to four times
daily
Sames as adult
(>6 yrs)
28
Leukotriene receptor antagonists
• Act by suppressing the effects of leukotrienes,
compounds that promote bronchoconstriction
as well as eosinophil infiltration, mucus
productions, & airway edema
• Help to prevent acute asthma attacks induced
by allergens & other stimuli
• Indicated for long-term treatment of asthma
29
• Dosage:
– Montelukast (5 & 10 mg tablets)
• Adult: 10 mg daily at bedtime
• Child:
– (2-5yrs) 4 mg daily at bedtime
– (6-14yrs) 5 mg daily at bedtime
30
• Adverse effects:
– GI disturbances
– Hypersensitivity reactions
– Restlessness & headache
– Upper respiratory tract infection
– Manufacturer advises to avoid these drugs in
pregnancy & breast-feeding unless essential
31
Management of Chronic Asthma for adults &
schoolchildren above 5yrs
Step 1: Occasional relief short-acting
beta2 agonist
Step 2: Add regular preventer therapy
Standard-dose inhaled corticosteroid
Step 3: Add long-acting inhaled beta2 agonist;
dose of inhaled corticosteroid may also be increased
Step 4: Add high dose of inhaled corticosteroids
Step 5: Add regular oral corticosteroid
E.g. prednisolone
• Stepping down:
– Review treatment every 3 months
– If symptoms controlled, may initiate stepwise
reduction
• Lowest possible dose oral corticosteroid
• Gradual reduction of dose of inhaled corticosteroid to
the lowest dose which controls asthma
35
Antihistamines
• H1 receptor antagonists
– Inhibit smooth muscle constriction in blood
vessels & respiratory & GI tracts
– Decrease capillary permeability
– Decrease salivation & tear formation
• Used for variety of allergic disorders to
prevent or reverse target organ inflammation
36
• All antihistamines are of potential value in the
treatment of nasal allergies, particularly
seasonal allergic rhinitis (hay fever)
• Reduce rhinorrhoea & sneezing but are
usually less effective for nasal congestion
• Are also used topically in the eye, in the nose,
& on the skin
37
• First-generation H1 receptor antagonists
– Non-selective/sedating
– Bind to both central & peripheral H1 receptors
– Usually cause CNS depression (drowsiness,
sedation) but may cause CNS stimulation (anxiety,
agitation), especially in children
– Also have substantial anticholinergic effects
38
Drug
Dosage
Adult
Child
Chorphenirami 4 mg q4-6hr, max: 24
ne (4 mg tablet, mg daily
2mg/ml Elixir &
expectorant)
1-2yrs: 1 mg twice daily
2-12yrs: 1- 2 mg q4-6h, Max:12
mg daily
Hydroxyzine
(25 mg tablet)
6 months-6yrs: 5-15 mg daily;
50 mg daily in divided dose if
needed
>6yrs: 15-25 mg daily; 50-100
mg daily in divided dose if
needed
25 mg at night; 25mg
three to four times
daily when necessary
Diphendramine 25-50 mg q4-6h
(10 mg/5ml
Elixir)
6.25-25 mg q4-8 hr ( >1 yr)
39
Drug
Dosage
Adult
Child
Promethazine
(10 & 25 mg
tablets,
5mg/5ml Elixir)
25 mg at night; 25 mg
twice daily if needed
2-10yrs: 5-25 mg daily in 1 to
2 divided dose
Azatadine (1 mg
tablet)
1 mg twice daily
1-12 yrs: 0.25-1 mg twice
daily
• Adverse effects:
– Sedation
– Dry mouth
– Blurred vision
– GI disturbances
– Headache
– Urinary retention
– Hydroxyzine is not recommended for pregnancy &
breast-feeding
• Second-generation H1 receptor
antagonists
– Selective/non-sedating
– Cause less CNS depression because they are
selective for peripheral H1 receptors & do not
cross blood-brain barrier
– Longer-acting compared to first-generation
antihistamines
42
Drug
Dosage
Adult
Child
Acrivastine
(Semprex)
8 mg three times
daily
Not recommended
Cetirizine (Zyrtec)
10 mg daily
5 mg daily / 2.5 mg twice daily
(2-6 yrs)
Desloratadine
(Aerius)
5 mg daily
1.25 mg daily (2-5 yrs)
2.5 mg daily (6-11yrs)
Fexofenadine
(Telfast)
120-180 mg daily
Not recommended
Loratadine
(Clarityne)
10 mg daily`
5 mg daily (2-5 yrs)
43
• Adverse effects:
– May cause slight sedation
– Some antihistamines may interact with antifungal,
e.g. ketoconazole; antibiotics, e.g. erythromycin;
prokinetic drug-- cisapride or grapefruit juice,
leading to potentially serious ECG changes e.g.
Terfenadine
44
Cough preparations
• There are three classes of cough preparations:
– Antitussives
– Expectorants
– Mucolytics
45
• Antitussives
– Drugs that suppress cough
– Some act within the CNS, some act peripherally
– Indicated in dry, hacking, nonproductive cough
that interfere with rest & sleep
46
Drug
Dosage
Codeine phosphate 25mg/5ml 15-30 mg three to four times
syrup
daily
Pholcodine 5mg/5ml Elixir
5-10 mg three to four times
daily
Dextromethorphan 10mg/5ml
in Promethazine Compound
Linctus
10-30 mg q4-8h
Diphenhydramine 10 mg/ 5ml
25 mg q4h, Max:150 mg daily
47
• Adverse effects:
– Drowsiness
– Respiratory depression (for opioid
antitussives)
– Constipation (for opioid antitussives)
– Preparations containing codeine or similar
analgesics are not generally recommended in
children & should be avoided altogether in
those under 1 year of age
48
• Expectorants
– Render the cough more productive by stimulating
the flow of respiratory tract secretions
– Guaifenesin is most commonly used
– Available alone & as an ingredient in many
combination cough & cold remedies
49
• Mucolytics
– Reacts directly with mucus to make it more watery.
This should help make the cough more productive
50
• Dosage
– Acetylcysteine
• 100 mg two to four times daily
• 200 mg two to three times daily
• 600 mg once daily
– Bromhexine
• 8-16 mg three times daily po
– Carbocisteine
• 750 mg three times daily, then 1.5 g daily in
divided doses
51
Nasal Decongestants
• Sympathomimetics are used to reduce
nasal congestion
• Stimulate alpha1-adrenergic receptors
on nasal blood vessels, which causes
vasoconstriction & hence shrinkage of
swollen membranes
52
• Topical administration:
– Response is rapid & intense
• Oral administration:
– Response are delayed, moderate & prolonged
53
Drug
Oxymetazoline
Formulation
Nasal Drops
0.025% 20 ml
Dosage
Adult
Child
-
2-3 drops q12h
(2-5 yrs)
Nasal Spray 0.05% 2-3 sprays q12h
15 ml
Phenylephrine
Nasal Drops 0.5%
10 ml
Xylometazoline
Nasal Drops 0.05% 2-3 drops q8-10h
/ 0.1%
(0.1%)
Same as adults
for children >6
yrs
Several drops q2- 4h
2-3 drops q8-10h
(2-12 yrs) (0.05%)
54
• Adverse effects:
– Rebound congestion develops with topical
agents when used for more than a few days
– CNS stimulation (such as restlessness,
irritability, anxiety and insomnia) occurs
with oral sympathomimetics
55
• Adverse effects (Cont’d):
– Sympathomimetics can cause vasoconstriction by
stimulating α-1 adrenergic receptors. More
common with oral agents
– Sympathomimetics cause CNS stimulation, and
can produce effects similar to amphetamine.
Hence, these drugs are subject to abuse
56
• Intranasal Corticosteroids
– Most effective for treatment of seasonal and
perennial rhinitis
– Have inflammatory actions and can prevent or
suppress all major symptoms of allergic rhinitis
including congestion, rhinorrhea, sneezing, nasal
itching and erythema
57
Drug
Beclomethasone
Dipropionate
Formulation
Nasal Spray
50 mcg /
dose
Dosage
Adult
Child
1 spray in
each nostril
four times
daily
Max. 10
sprays / day
4-6 sprays /
day
Nasal Spray 2 applications
50 mcg dose into each
(Aqueous)
nostril twice
to four times
daily
Max. 400 mcg
daily
Same as adult
(>6 yrs)
Not
recommended
in children
<6yrs
58
Drug (Cont’d)
Budesonide
Formulation
Dosage
Adult
Child
Nasal Spray 50
mcg / dose
(Aqueous)
1-2 sprays into
each nostril
twice daily; after
2-3days: 1
spray into each
nostril twice
daily
Not
recommended
for age 12 yrs or
below
Turbuhaler
100mcg / dose
400 mcg in the
morning given
as 2
applications into
each nostril;
then reduce to
the smallest
amount
necessary
-
Drug
Formulation
Dosage
Adult
Child
1 spray into each
nostril in the
morning (4-11yrs)
Max: 4
sprays/day
Fluticasone
Nasal Spray 50
mcg / dose
(Aqueous)
2 sprays into
each nostril in
the morning
Max: 8
sprays/day
Mometasone
Nasal Spray 50
mcg / dose
2 sprays in each
1 spray in each
nostril once daily; nostril once daily
1spray in each
(3-11yrs)
nostril as
maintenance
Max: 8
sprays/day
• Adverse effects:
– Mild
– Most common effects are drying of nasal
mucosa & sensations of burning or itching
61
Chronic Obstructive Pulmonary Disease (COPD)
• Umbrella term for various conditions characterized by
limitation of airflow that is not fully reversible
• Chronic airflow limitation caused by a mixture of small airway
disease and parenchymal destruction
• Airflow limitation is often progressive
• Associated with an abnormal inflammatory response of lungs
to noxious substances
• PREVENTABLE and TREATABLE disease
62
Relationship between COPD and
emphysema/chronic bronchitis
• Emphysema
– Destruction of the gas exchanging surfaces of the lung (alveoli)
– Pathological term that describes only one of several structural
abnormalities present in patients with COPD
• Chronic bronchitis
– Presence of cough and sputum production for at least 3 months in each of
two consecutive years
– Remains a clinically and epidemiologically useful term, but does not
reflect the major impact of airflow limitation on morbidity and mortality in
COPD patients
• The emphasis on these conditions are not included in the definition of
COPD in current relevant clinical guidelines
63
Asthma and COPD
• Underlying cause is different
– Asthma: eosinophilic inflammation
– COPD: neutrophilic inflammation
• COPD can coexist with asthma
• While asthma can usually be distinguished
from COPD, in some individuals with chronic
respiratory symptoms and fixed airflow
limitation it remains difficult to differentiate
the two diseases
64
Pharmacotherapy
• None of the current available medications can alter the
natural course of COPD or modify the rate of decline in lung
function
• Aims (as per GOLD report)
–
–
–
–
–
–
–
Relieve symptoms
Prevent disease progression
Improve exercise tolerance
Improve health status
Prevent and treat complications
Prevent and treat exacerbations
Reduce mortality
65
Bronchodilators
• Bronchodilator medications are central to
symptom management in COPD
• Inhaled therapy is preferred
• The choice between beta agonist,
anticholinergic, theophylline, or combination
therapy depends on availability and individual
response in terms of symptom relief and side
effects
66
• Bronchodilators are prescribed on an asneeded or on a regular basis to prevent or
reduce symptoms
• Long-acting inhaled bronchodilators are more
effective and convenient
• Combining bronchodilators may improve
efficacy and decrease the risk of side effects
compared to increasing the dose of a single
bronchodilator
67
Corticosteroids
• Effects of oral and inhaled corticosteroids in
COPD are much less dramatic than in asthma,
and their role in the management of stable
COPD is limited to specific indications
68
Oral corticosteroids
• Use of a short course (two weeks) of oral
corticosteroids to identify COPD patients who
might benefit from long-term treatment with
oral or inhaled corticosteroids is
recommended
• Due to lack of evidence of benefit, and the
issue of side effects, long-term treatment with
oral corticosteroids is not recommended in
COPD
69
Inhaled corticosteroids
• Regular treatment is appropriate for
symptomatic Stage III and Stage IV CPOD and
repeated exacerbations (for example, 3 in the
last 3 years)
• Treatment has been shown to reduce the
frequency of exacerbations and thus improve
health status
• More effective when combined with a longacting beta agonist
70
• Drugs acting on the respiratory system,
especially for asthma, can be administered by
inhalation, the advantages are:
– Enhance therapeutic effects
– Minimize systemic effects
– Rapid relief of acute attacks
71
• There are various types of inhalation devices:
– Metered-dose inhalers (MDIs)
• Pressurized devices that deliver a measured dose of
drug with each activation
• With CFC or non-CFC propellant
• Hand-mouth coordination is required
72
• Spacers:
– Use with MDIs
– Increase delivery of drug to the lungs & decrease deposition
of drug on the oropharyngeal mucosa
– Especially important for inhaled corticosteroids
73
– Dry-powder inhalers (DPIs)
•
•
•
•
Include Turbuhalers & Accuhalers
Drugs are in the form of dry, micronized powder
No propellant is employed
Breath activated, much easier to use
74
– Nebulizers
• Small machine to convert a drug solution into mist
• Droplets in the mist are much finer than those
produced by inhalers
• Through face mask or mouth piece held between the
teeth
• Take several minutes to deliver the same amount of
drug contained in 1 puff from an inhaler
75