Drugs used in Bronchial Asthma

1. Drugs for
Bronchial
Asthma
Dr. Sanooz Raheem

2. Objectives:
• Outline the various groups of drugs used in the management of Bronchial Asthma
• Describe the pharmacological properties of the following drugs
Salbutamol
Terbutaline
Salmeterol
•
List the pharmacological actions of Methyl xanthines
• Describe the pharmacological properties of Theophylline
• List examples of anticholinergics
• Describe the pharmacological properties of Ipratropium Bromide
• List examples of Mast cell stabilizers
• Describe the role of Mast cell stabilizers in the management of bronchial asthma
• Describe the pharmacological properties of Sodium chromoglycate
• Explain the role of Corticosteroids in the management of bronchial asthma
• List examples & their pharmacological properties of corticosteroids used in the management
of bronchial asthma
• Outline the management of Acute severe Asthma (Status asthmaticus)

3. Bronchial asthma
• An inflammatory condition
• Hyper responsiveness of tracheobronchial smooth muscles to variety of stimuli
• Results in
- Narrowing of air tubes
- Increased secretion
- Mucosal oedema
- Mucus plugging
• Symptoms:
- dyspnoea, wheezing, cough, limitation of activity

6. Pathophysiology

7. Bronchial asthma
Types of asthma based on etiology:
• Extrinsic asthma:
• Allergy-induced
• Commonly suffer from other atopic diseases
• Mostly episodic, Less prone to status asthmaticus
• Intrinsic asthma:
• No immunological basis for their condition
• Perennial
• More prone to status asthmaticus

8. Bronchial asthma
• Types of Asthma based on clinical condition:
• Mild episodic asthma:
• Seasonal asthma:
• Mild chronic asthma:
• Moderate asthma with frequent exacerbations:
• Severe asthma:
• Status asthmaticus/Refractory asthma

9. Approach for treatment of Asthma

10. Approaches to treatment
1. Prevention of AG:AB reaction- avoid antigen
2. Neutralization of IgE- Omalizumab
3. Suppression of inflammation and bronchial hyperactivity-
corticosteroids
4. Prevention of release of mediators- mast cell stabilizers
5. Antagonism of released mediators- leukotriene antagonists,
antihistamines, PAF antagonists
6. Blockade of constrictor neurotransmitter- anticholinergics
7. Mimicking dilator neurotransmitter- sympathomimetics
8. Directly acting bronchodilators- methylxanthines

11. Drug administration
• Inhalation:
- Directly delivers the drug to airways
- Dose required is less
- Side effects reduced
• Oral:
- If inhalation is not possible
- Systemic side effects
• Parenteral:
- Beta agonists, corticosteroids, aminophylline can be given
- Given when inhalational drugs are inadequate

12. Classification of drugs for asthma
• BRONCHODILATORS:
1. β2-Sympathomimetics: Salbutamol, Terbutaline, Bambuterol,
Salmeterol, Formoterol, Ephedrine
2. Methyl Xanthines: Theophylline, Aminophylline, Choline
theophyllinate, Hydroxyethyl theophylline, Doxophylline.
3. Anticholinergics: Ipratropium bromide, Tiotropium bromide
• LEUKOTRIENE ANTAGONISTS: Montelukast, Zafirlukast
• MAST CELL STABILIZERS: Sodium cromoglycate, Ketotifen
• CORTICOSTEROIDS
1. Systemic: Hydrocortisone, Prednisolone
2. Inhalational: Beclomethasone, Budesonide, Fluticasone,
Flunisolide
• ANTI Ig-E ANTIBODY: Omalizumab

13. Sympathomimetics
• Bronchodilataion
• Minimal effect on airway when inflammation is chronic
• Mechanism of action:
• β2 stimulation increased cAMP formation in bronchial muscle
cellrelaxation
• Increases cAMP in mast cells and other inflammatory cells
• Also decreases mediator release
• Should be used cautiously in hypertensives, IHD, ptn on digitalis
• Most effective and fast acting bronchodilator on inhalation
• E.g. Salbutamol, Terbutaline, Bambuterol, Salmeterol, Formoterol, Ephedrine
• Short acting used for immediate relief and long acting for prophylaxis with steroid

14. Short acting:
Mild to mod. Symptoms responds
rapidly to inhalation
Regular treatment with short acting
inhalation less effective
Not appropriate prophylactic Tx
Inhalation before exercise reduces
exercise induced asthma
EX: salbutamol, Terbutaline
Long acting:
Ex: Formoterol, Salmetrol
Given as inhalation
Used only in ptns with regular steroid
inhalation
Long term control of asthma and
nocturnal asthma control
Salmetrol no relief in asthma attack
Formoterol short term symptom
relief and prevention of exercise
induced bronchospasm

15. Find out the recommendations
to use long acting beta2
agonists in BA?

16. Sympathomimetics
Salbutamol
• Highly selective β2 agonist
• Less prominent cardiac side effects
• Inhaled Salbutamol produces bronchodilatation in 5 min and
action lasts for 2-4 hrs
• Side effects: Palpitations, restlessness, nervousness, throat
irritation, ankle edema, muscle tremors, Hypokalaemia
• Not suitable for round the clock prophylaxis, but terminates
attacks of asthma
• Oral preparations: presystemic metabolism, bioavailability 50%,
duration 4-6 hours
• Use of oral salbutamol: Reserved for patients who cannot
correctly use inhalers, Used as an adjuvant in severe asthma

17. Dose
• Oral
Adults 4mg 3-4 times/day, max single dose 8mg, elderly start with 2mg
Children 2-6yrs 3-4times/day, 6-12 yrs 2mg 3-4times/day
• IV injection- 250mic.g, repeat if necessary
• IV infusion- 5mic.g/minute initially, adjust according to response & HR
3-20mic.g/min range
• Aerosol- 100-200 mic.g upto 4 times/day, children 100-200mic.g upto
4 times/day
• Inhalation of powder- 200-400mic.g upto 4times/day
• Nebulize- 2.5-5mg 4times/day or more

18. Terbutaline:
• Similar to Salbutamol
• Dose:
Orally 2.5mg tds initially and upto 5mg tds later
• Inhaled Salbutamol and Terbutaline are currently the most popular
drugs for quick reversal of bronchospasm
• Regular use of both does not reduce bronchial hyperactivity – long
term use reduced responsiveness
• Beta2 receptors down regulated on long term use
• Long term use - long acting beta2 agonists
• Short acting drugs- symptomatic relief of wheezing

19. Sympathomimetics
Salmeterol:
• It is the first long acting selective β2 agonist (LABA) with slow onset of
action
• Used by inhalation on a twice daily schedule
• Used for maintenance therapy and nocturnal asthma
• Not useful for acute asthma
• More beta2 selective than salbutamol
• In long term used with corticosteroids
Dose: adult 50mic.g – 100mic.g twice daily
child 5-12 yrs 50mic.g twice daily

20. Formeterol:
• Another LABA
• Acts for 12 hrs
• Compared to Salmeterol it has faster onset of action

21. Preparations
• Inhalation:
Pressurized MDI- mild to moderate asthma
Adding a spacer device improve drug delivery
Salbutamol, terbutaline, fenoterol- 3-5 hrs of duration of action
Salmetrol, formoterol- 12hrs
Nebulizer- salbutamol/terbutaline solution used
Severe asthma with oxygen
• Oral: when inhalations can not be managed by ptns
• Parenteral: salbutamol/ terbutaline in severe or life threatening asthma
Monitor, adjust dose – response, HR

22. Cautions
• Hyperthyroidism
• Cardiovascular disease
• Arrhythmias
• Susceptibility to QT prolongation
• Hypertension
• Diabetes- monitor blood sugar
** can lead to hypokalemia, special concern

23. Methyl Xanthines
• Naturally occuring Methyl Xanthine alkaloids are Caffein,
Theophylline and Theobromine
• Mechanism of action:
• Inhibition of phosphodiesterase (PDE)  increased cAMP
Bronchodilatation, cardiac stimulation, vasodilation
• Blockade of adenosine receptorsrelaxes smooth muscles
• Release of Ca2+
from sarcoplasmic reticulum, especially in
skeletal and cardiac muscle (only at higher concentrations)
• E.g: Theophylline, Aminophylline, Choline theophyllinate,
Hydroxyethyl theophylline, Doxophylline

24. Methyl Xanthines
• Theophylline:
• Well absorbed orally
• T1/2 is 7-12 hrs
• Distributed in all tissues
• 50% plasma protein bound
• Metabolized in liver
• Toxic dose is close to therapeutic dose
• T ½ variation is important
• Aminophylline- theophylline+ ethylenediamine, given IV very slowly,
SE- convulsions, arrhythmia
• Caution: cardiac disease, Htn, hyperthyroidism, peptic ulcer, elderly, epilepsy,
hypokalemia

25. • Dose reduction needed in
- Age > 60 yrs
- CHF
- Pneumonia
- Liver failure , viral infections
• Has narrow margin of safety
• Additive effect with Beta2 agonist- increase SE, hypokalaemia
• Side effects: headache, nervousness, nausea, CNS toxicity in children, gastric
pain (with oral), rectal inflammation (with rectal suppositories), pain at site of
injection (i.m), Rapid IV can cause precordial pain, syncope and sudden death,
hypotension, palpitations, tremor, insomnia

27. Interactions:
metabolism is induced by smoking, phenytoin, rifampicin,
phenobarbitone
Metabolism is inhibited by erythromycin, ciprofloxacin, cimetidine,
OCPs, allopurinol
Theophylline induces the effects of- furosemide, sympathomimetics,
digitalis, oral anticoagulants, hypoglycaemics
Reduces the effects of- phenytoin, lithium
Uses: Bronchial asthma and COPD, Apnoea in premature infant,

28. Anticholinergics
• Atropinic drugs cause bronchodilatation by blocking M3 receptor
mediated cholinergic constrictor tone
• Short term relief
• Act primarily in larger airways
• Produce slower response than inhaled sympathomimetics
• Better suited for regular prophylactic use
• Combination of inhaled Ipratropium with β2 agonists produce more
marked and longer lasting bronchodilatation.
• Refractory asthma treated with combination preparations

29. • PK: maximal effect by 30-60min use, duration of action 3-6hrs,
• Caution: BPH, BOO, angle-closure glaucoma
• SE: dry mouth, constipation, cough, paradoxical bronchospasm,
headache, rarely N, AF, urinary retention,
• E.g: Ipratropium bromide- shorter acting,
Dose- aerosol inhalation20-40mic.g 3-4 times/day, powder inhalation-
40mic.g 3-4times/day, nebulize 250-500 mic.g 3-4 times/day
• Tiotropium bromide-longer acting

30. Leukotriene antagonists
• Cystenyl leukotrienes important mediators in bronchial asthma
• Competitively antagonize cysLT1 receptor mediated bronchoconstriction,
increased vasodilatation and recruitment of eisonophils
• Indicated for prophylactic therapy of mild to moderate asthma as alternative to
inhaled glucocorticoids- efficacy low
• May obviate need for inhaled glucocorticoids
• Additive effect with steroids and long acting beta2 agonists
• Safe drugs in children
• No value in COPD

31. • Side effetcs: headache, rashes, Churg-Strauss syndrome
• PK: well absorbed orally, highly plasma protein bound, T ½ Monte-3-6
hrs, Zafir- 8-12 hrs
• E.g: Montelukast, Zafirlukast
• Dose: Montelukast- adult 10mg once/day evening, 6-15 yrs 5mg/day

32. Mast cell stabilizers
Sodium Cromoglycate
•Given 4-6wks to assess response , dose adjusted according to response
•Dose withdrawal done gradually
•Inhibits degranulation of mast cells
•Release of asthma mediators inhibited
•Chemotaxis of inflammatory cells inhibited
•Long term Tx- decreases cellular immunity response, reduced bronchial hyperactivity,
•Less effective in prophylaxis compared to steroids
•No brochodilatation- not suitable for acute asthma

33. • PK: not absorbed orally, given as aerosol,
• Use: BA, Allergic rhinitis, Allergic conjunctivitis
• AR: systemic toxicity minimal, rarely nasal congestion, headache,
dizziness, arthralgia, rashes
• Dose: 10mg 4-8 times/day

34. Ketotifen
•An antihistamine
•Stimulation of immunogenic, inflammatory cells and mediator release are
reduced
•Not a bronchodilator
•Long term use can provide mild symptomatic relief
•Use: BA, atopic dermatitis, perennial rhinitis, conjunctivitis, urticaria, food
allergy
•AR: well tolerated, sedation, dry mouth, dizziness, nausea, weight gain

35. Corticosteroids
• These do not cause bronchodilatation,
• Reduce bronchial hyper-reactivity, mucosal edema, by
supressing inflammatory response to AG:AB reaction
• More complete and sustained symptomatic relief than
bronchodilators/ cromoglycate
• Improve airflow, reduce asthma exacerbations, influence
airway remodeling and retard disease progression
• Increase airway smooth muscle responsiveness to Beta2
agonists
• Takes 3-7 days to alleviate symptoms after starting Tx

36. Regular corticosteroid inhalation needed
• If ptn requires beta2 agonist more than twice a week
• If symptoms disturb sleep more than once a week
• If the patient has suffered exacerbations in last 2 years requiring a
systemic steroid or nebulized bronchodilator
** regular use of inhaled steroids reduce the exacerbtions

37. • Two forms are used Systemic and Inhalational
1. Systemic/Oral Cortico Steroid (OCS)
• Used in severe chronic asthma and Status asthmaticus
• E.g: Hydrocortisone, Prednisolone
1. Inhalational Cortico Steroid (ICS)
• Step one for all asthma patients- airway inflammation and bronchial remodeling
from beginning
• Safe during pregnancy
• Benefits: suppress bronchial inflammation, increase PEFR, reduce need for rescue
beta2 agonist inhalations, prevent acute episodes of asthma
• No role during acute asthma
• Peak effect by 4-7 days and effects last for few weeks after discontinuation of Tx
• Side effetcs:hoarseness of voice, dysphonia, sore throat, oropharyngeal candidiasis ,
systemic effects if higher doses inhaled for longer duration-adrenal suppression
• E.g: Beclomethasone, Budesonide, Fluticasone, Flunisolide

38. Oral corticosteroid Tx
• Acute attack with short course of oral steroid
• If ptn on inhalers can stop oral Tx abruptly
• Taper in ptns on several courses of steroids/ period of maintanence
• In chronic asthma if response to other drugs inadequate long term
administration of oral corticosteroid
• If ptns on long term oral steroid transfer slowly to inhalers
• Given as single dose in the morning

39. Budesonide:
•High topical systemic activity ratio
•Small amount absorbed and rapidly
metabolized
•Less systemic effects
•Dose: 200-400mic.g bd-qid
200-400mic.g/day in allergic
rhinitis
•SE: nasal irritation, sneezing,
crusting, itching of throat, dryness
•CI: presence of infection/nasal
ulcers
Fluticasone propionate:
•High potency
•Longer duration of action
•Negligible oral bioavailability
•Dose 100-250mic.g bd, max
1000mic.g/day

40. Pharmacokinetics of inhaled
corticosteroids

41. Anti-IgE antibody
Omalizumab:
Humanized monoclonal antibody against IgE
Given S.C
Neutralizes free IgE in circulation
Useful in severe extrinsic asthma

44. What is inhaler?
• An inhaler is a medical device used for delivering
medication into the body via the lungs.

45. Inhaler devices
Different inhaler devices suit different people. Inhaler
devices can be divided into four main groups:
•Pressurised metered dose inhalers (MDIs).
•Breath-activated inhalers - MDIs and dry powder inhalers.
•Inhalers with spacer devices.
•Nebulisers.

46. Devices
Metered-dose inhalers

47. Properties
A liquid propellant
Inhalation technique is critical for optimal drug delivery

49. Common errors include:
•Not shaking the inhaler before using it.
•Inhaling too sharply or at the wrong time.
•Not holding your breath long enough after breathing
in the contents.

50. How to use
Without chamber

51. To use an MDI:
•Shake the inhaler well before use (3 or 4 shakes)
•Remove the cap
•Breathe out, away from your inhaler
•Bring the inhaler to your mouth. Place it in your mouth between your teeth and
close you mouth around it.
•Start to breathe in slowly. Press the top of you inhaler once and keep breathing in
slowly until you have taken a full breath.
•Remove the inhaler from your mouth, and hold your breath for about 10 seconds,
then breathe out.
•Metered Dose Inhaler
•If you need a second puff, wait 30 seconds, shake your inhaler again, and repeat
steps 3-6. After you've used your MDI, rinse out your mouth and record the number
of doses taken.
•Store all puffers at room temperature

53. Cleaning Your MDI
To clean your MDI, follow the instructions that came with
it. In most cases, they will advise you to:
1.Remove the metal canister by pulling it out.
2.Clean the plastic parts of the device using mild soap
and water. (Never wash the metal canister or put it in
water.)
3.Let the plastic parts dry in the air (for example, leave
them out overnight).
4.Put the MDI back together.
5.Test the MDI by releasing a puff into the air.

54. Advantages Vs Disadvantages
Advantages
•Rapid application
•Handling
•Multidose
Disdvantages
•Hand-breathe
coordinations
•İneffective use in poor
ventilated patients
•Oropharyngeal
deposition and local
side effects

55. Spacers
Also known as aerosol-holding
chambers, add-on devices and spacing
devices, spacers are long tubes that
slow the delivery of medication from
pressurized MDIs.

56. With chamber

57. Using a Spacer:
1.Shake the inhaler well before use (3-4 shakes)
2.Remove the cap from your inhaler, and from your spacer, if it has
one
3.Put the inhaler into the spacer
4.Breathe out, away from the spacer
5.Bring the spacer to your mouth, put the mouthpiece between your
teeth and close your lips around it
6.Press the top of your inhaler once
7.Breathe in very slowly until you have taken a full breath. If you
hear a whistle sound, you are breathing in too fast. Slowly breath
in.
8.Hold your breath for about ten seconds, then breath out.

59. Cleaning Your Spacer
To clean your spacer, follow the instructions that come
with it. In most cases, they will advise you to:
1.Take the spacer apart.
2.Gently move the parts back and forth in warm water
using a mild soap. Never use high-pressure or boiling hot
water, rubbing alcohol or disinfectant.
3.Rinse the parts well in clean water.
4.Do not dry inside of the spacer with a towel as it will
cause static. Instead, let the parts air dry (for example,
leave them out overnight).
5.Put the spacer back together.

60. Dry powder inhalers

61. DISKUS®
A DISKUS® is a dry-powder inhaler that holds 60 doses.
It features a built-in counter,

62. using DISKUS®:
1.Open your DISKUS®: Hold it in the palm of your hand,
put the thumb of your other hand on the thumb grip and
push the thumb grip until it "clicks" into place
2.Slide the lever away from you as far as it will go to get
your medication ready
3.Breathe out away from the device
4.Place the mouthpiece gently in your mouth and close
your lips around it
5.Breathe in deeply until you have taken a full breath
6.Remove the DISKUS® from your mouth
7.Hold your breath for about ten seconds, then breathe
out
8.Always check the number in the dose counter window

63. If you drop your DISKUS® or breathe into it after its dose has been loaded, you may
cause the dose to be lost. If either of these things happens, reload the device before
using it.

64. Turbuhaler®
A Turbuhaler® is a dry-powder inhaler available in an easy-to-
use format.
Clean your
Turbuhaler® as
needed. To do this,
first wipe the
mouthpiece with a
dry tissue or cloth.
Never wash the
mouthpiece or any
other part of the
Turbuhaler® - if it
gets wet, it won't
work properly.

65. How to use a Turbuhaler®:
1.Unscrew the cap and take it off. Hold the inhaler upright
2.Twist the coloured grip of your Turbuhaler® as far as it will go.
Then twist it all the way back. You have done it right when you hear a
"click"
3.Breathe out away from the device
4.Put the mouthpiece between your teeth, and close your lips around
it. Breathe in forcefully and deeply through your mouth
5.Remove the Turbuhaler® from your mouth before breathing out
6.Always check the number in the side counter window under the
mouthpiece to see how many doses are left.
7. When finished, replace the cap.

66. Diskhaler®
A Diskhaler® is a dry-powder inhaler that holds small pouches (or
blisters), each containing a dose of medication, on a disk.
The Diskhaler® punctures each blister so that its medication can be
inhaled.

67. To use your Diskhaler®:
1.Remove the cover and check that the device and mouthpiece are clean.
2.If a new medication disk is needed, pull the corners of the white cartridge out as far as it
will go, then press the ridges on the sides inwards to remove the cartridge.
3.Place the medication disk with its numbers facing up on the white rotating wheel. Then
slide the cartridge all the way back in.
4.Pull the cartridge all the way out, then push it all the way in until the highest number on
the medication disk can be seen in the indicator window.
5.With the cartridge fully inserted, and the device kept flat, raise the lid as far as it goes, to
pierce both sides of the medication blister.
6.Move the Diskhaler® away from your mouth and breathe out as much as you can until no
air is left in your lungs.
7.Place the mouthpiece between your teeth and lips, making sure you do not cover the air
holes on the mouthpiece. Inhale as quickly and deeply as you can. Do not breathe out.
8.Move the Diskhaler® away from your mouth and continue holding your breath for about
10 seconds.
9.Breathe out slowly.
10.If you need another dose, pull the cartridge out all the way and then push it back in all
the way. This will move the next blister into place. Repeat steps 5 through 9.
11.After you have finished using the Diskhaler®, put the mouthpiece cap back on.

70. How to use a spacer
1.Take off the cap and shake the inhaler
2.Put the inhaler into the end of your spacer
3.Breathe out gently as long as feels comfortable
4.Put the mouthpiece between your teeth and lips, making a
seal so no medicine can escape
5.Press the canister to put one puff of your medicine into the
spacer
6.Breathe in slowly and steadily (not hard and fast) through
the mouthpiece
7.Remove the spacer from your mouth and hold your breath
for 10 seconds (or for as long as is comfortable) then breathe
out slowly
8.If you need a second dose, wait 30 seconds, remove the
inhaler, shake it and repeat the steps above.

72. How to help your child use a spacer
1.Explain to your child what's going to happen and what they need to do
2.Remove the cap and shake the inhaler - your child can help with this
3.Put the inhaler into the end of the spacer
4.Place the mouthpiece between your child's teeth and lips, making a seal so no
medicine can escape
5.Press the canister once to put one puff of your child's inhaler medicine into the
spacer
6.Get them to breathe in and out of the mouthpiece five times
7.Repeat from step 2 for each puff of the inhaler needed, remembering to take
out the inhaler and shake it before each puff

74. 1.Remove the cap and shake the inhaler
2.Place the inhaler in the end of the spacer
3.Put the mask over your child's nose and mouth, making a good seal so no
medicine can escape
4.Press the canister once so that one puff of medicine goes into the inhaler
5.Count to 10 slowly (in your head, say 'One, and two, and three, etc' to get
the timing right)
6.If you need to give further doses, repeat all the steps again, remembering to
remove the inhaler and shake it between puffs
7.Wipe your baby's face afterwards, to remove any medicine that might have
landed on their skin
How to use a spacer and a mask with your baby

75. Cleaning spacer
Wash your spacer once a month using detergent, such as washing-up liquid.
Don't scrub the inside of the spacer as this affects the way it works. Leave it
to air-dry as this helps to prevent the medicine sticking to the sides of the
chamber and reduces the static.
Wipe the mouthpiece clean of detergent before you use it again.
Don't worry if your spacer looks cloudy - that doesn't mean it's dirty.

79. AEROSOL DELIVERY METHOD AGE OF PATIENT
Dry powder inhaler Five years or older
MDI Older than five years
MDI with chamber Older than four years
MDI with chamber and mask Four years or younger
MDI with endotracheal tube Neonate
Small-volume nebulizer Two years or younger
General Age Requirements for Correct Use of Various Aerosol Delivery Devices