Duration of action: SABA: 6 h LABA: 12 h Ultra LABA: 24 h Indacaterol is considered an ultra long acting beta agonist Bambuterol is converted in the body to terbutaline
SABD: short acting bronchodilator LABD: long acting bronchodilator
3 Asthma and COPD Management
• It is an asthma episode characterized by progressive
increase in symptoms and progressive decline in lung
functions sufficient to require a change in treatment.
• Occasionally occurs as the 1st
presentation of asthma.
• Usually occurs in response to exposure to an external
agent (viral infection, allergen) or poor adherence to
• Exacerbations may be poorly perceived by persons in
whom respiratory function declines out of proportion to
• Management may be started by the patient (self
management) until hospital care, if needed, is provided.
Asthma Exacerbation Self Management
• Repeated dosing with inhaled SABA provides temporarily
relief until the cause of worsening symptoms passes or
increased controller treatment had time to make effect.
• Higher ICS may help prevent worsening asthma
progressing to a severe exacerbation.
• High dose ICS for 7 – 14 days have an equal effect to
a short course of OCS.
Combined ICS + Rapid Onset LABA (Formeterol) Inhaler
• Used as both controller and reliever.
• If used during early stage of worsening asthma, it may
• For most patients, the written asthma action plan should
provide instructions for when and how to start OCS.
o Failed response to ↑ controller and reliever
medications for 2 – 3 days.
o Rapid deterioration of symptoms.
o FEV1 or PEF < 60% of predicted or personal best.
o History of sudden severe exacerbation.
o Previous exacerbation requiring OCS.
• Dose: Prednisone or equivalent, once daily in the morning
o Adults: 40 – 50 mg / day for 5 – 7 days.
o Children 1 – 2 mg/kg/day (up to 40 mg) for 3 – 5 days.
Asthma Exacerbation Hospital Management
• By nasal cannula or mask to achieve SO2 93 – 95%
• The most cost effective and efficient delivery system is by
pMDI with a spacer. Nebulizer may be used in the critically ill.
Adrenaline SC or IM may be used only for treatment of
asthma associated with anaphylaxis or angioedema.
OCS should be used in all but the mildest exacerbations in
adults; should be given within 1 hour of presentation.
IV route may be used in case of vomiting or severe dyspnoea
eg, Hydrocortisobe 100 – 200 mg / 6 – 8 h
Ipratropium inhaled with other bronchodilators
(Ventolin + Atrovent + Pulmicort)
Magnesium Sulphate 2 gm IV infusion over 20 mins.
It may be used in patients with persistent hypoxemia who
fail to respond to initial treatment.
Antibiotics Not recommended unless there is strong
evidence of infection.
Do NOT Give:
• Poor efficacy, high toxicity.
• IV aminophylline is associated with severe and potentially
fatal SE, particularly in patients already treated with
sustained release theophylline.
Sedatives / Narcotics should be strictly avoided as they
cause respiratory depression.
Patients should not be seadted in order to receive ventilation.
Aspirin Exacerbated Respiratory Disease
In addition to guideline based management of asthma and sinus disease:
NSAID Avoidance Alternatives are selected according to their
potential to cross react with aspirin (and cause the same problem).
This potential is based on the degree of COX1 inhibition.
Leukotriene Receptor Antagonists (LTRAs)
• Should be part of any treatment course of AERD to deal
with the actual dysregulation of leukotriene production and
safeguard patients from severe reaction to accidental NSAID
• If patients do not improve after using LTRAs for 4 – 6 days,
Zileuton (5 lipoxygenase inhibitor) may be added. This
drug was recognized by AERD patients as “very effective”
more frequently than LTRAs, but it requires periodic
monitoring of liver functions.
Group Potential of Cross Reaction with
At time of 1st
with low dose
Occasional, with high dose Paracetamol
With high dose, mild reaction Meloxicam
Should not cross react
(no controlled trial)
No potential to cross react Tramadol
• Almost all AERD patients can be effectively desensitized to aspirin.
• Effects on rhinosinusitis are usually more dramatic than on BA.
o Nasal polyposis that recurs or becomes worse after surgery
despite LTMAs and nasal steroids.
o Inflammatory disease requiring daily NSAIDs, eg, RA.
o Compelling indications for aspirin as CVD, recurrent headache.
• Aspirin is given daily for 1 month, eg, 650 mg twice daily, then dose is
• Patient specific optimal doses are not predictable.
Omalizumab 4 – 8 doses given in line with dosing recommendations for
BA (according to serum IgE level and body weight) → substantial
reduction in total endoscopic nasal polyposis score.
Mepolizumab 2 IV doses, 4 weeks apart also significantly ↓ nasal
Sympathomimetics used as Bronchodilators
Adrenaline amp 1 mg Adrenaline (Epinephrine)
Isoprenaline amp 0.2 mg Isuprel / Isoprenol
Salbutamol inhaler, syp, tab, cap Ventolin / Vental
i soln Farcolin
Terbutaline syp, tab, cap Bricanyl / Aironyl
Bambuterol syp, tab Bambec
Fenoterol inhaler, syp, tab Berotec
Salmeterol inhaler Serevent / Metrovent
Formeterol inhaler, i cap Foradil / Metrohaler
Indacaterol i cap Onbrez
Short Acting (6 h)
Long Acting (24 h)
Ipratropium inhaler, vial for nebulizer Atrovent
Tiotropium i cap Spiriva
Aminophylline amp 500 mg Aminophylline
Theophylline cap 100, 200, 300 mg Theo SR
tab 300 mg Quibron
supp 100, 300 mg Amriphylline
syp 100 mg/5mL Amriphylline
Budesonide i vial 0.25, 0.5 mg (2) Pulmicort
Beclomethasone inhaler Beclosone
• Inhaled steroids are the most effective anti-
inflammatory medications for treatment of asthma.
• Most of the clinical benefit from ICS is seen at low
• Add on therapy with another controller (eg, LABA) is
preferred over increasing the dose of ICS.
• However, some patients with severe asthma may
benefit from long term treatment with higher doses of
LABA + ICS
SABA + SAMA
SABA + Expectorant
Formeterol + Budesonide Symbicort Turbohaler
Salmeterol + Fluticasone Seretide Diskus
Salbutamol + Ipratropium Combivent Inhaler
Salbutamol + Guaiphenesin Ventolin Expectorant
Salbutamol + Ammonium Chloride Farcolin
Leukotriene Modifying Agents (LTMAs)
• Cysteinyl leukotrienes (CyLts) are 1000 times more potent than
histamine in causing airway obstruction and their effect lasts
• LTRAs are particularly useful in
o EIB: If given 2 hours before exercise, they ↓ FEV1 decline after
o To improve asthma control not completely achieved with
steroids and also as steroid sparing drugs. Since LTRAs are
given systemically, they suppress the airway inflammation
beyond the reach of inhaled steroids.
Side effects are not significantly different from placebo.
Commonest SE: headache, GIT upset
Effect of Food on
Drug Interactions ---------- ↑ Plasma level of
Use in Hepatic
• Severe persistent allergic asthma with elevated serum IgE
(confirmed IgE dependent allergic asthma).
• Chronic idiopathic urticaria which remains symptomaic despite
treatment with antihistaminics.
- Not Indicated for:
• Other forms of urticaria or other allergic conditions.
• Acute bronchospasm or status asthmaticus.
- Mechanism of Action:
• ↓ IgE receptors (Fc receptors) on surface of mast cells,
• ↓ Binding of IgE to its receptors on these cells.
• ↓ Serum free IgE.
• Requires regular injection and observation after each injection.
• Boxed Warning: Anaphylaxis, presenting as bronchospasm,
hypotension, syncope, angioedema of throat or tongue occurred
after administration. It has occurred after the 1st
dose and also
beyond one year after start of treatment. Patient should be
closely observed after injection with available facilities to
manage anaphylaxis which can be life threatening.
- Reconstitution of Lyophilized Vial:
• The powder takes 15 – 20 mins to dissolve.
• The solution is viscous and slightly opalescent.
• It should be used within:
o 4 h (room temp).
o 8 h (2 - 8 O
• Administration should be slow and forceful enough.
- Dose: 75 – 375 mg SC every 2 – 4 weeks.
- Dose and dosing frequency are determined according to body
weight and serum IgE level measured before start of treatment.
- IgE levels remain elevated for up to 1 year after discontinuation of
treatment, so, retesting during treatment can not be used as a guide
- Follow Up:
• The main outcome measure is frequency and severity of
asthma attacks and exacerbations.
• If the patient does not respond within 4 months of starting
treatment, it is unlikely that further administration will be
- Adverse Reactions:
- Anaphylaxis which may be life threatening.
- Serum sickness: fever, arthralgia, rash.
- Eosinophilc conditions: eosinophilia, vasculitic rash, worsening
- Commonest reactions: arthralgia, pain, fatigue, dizziness,
- Injection site reactions: redness, warmth, burning sensation.
These generally ↓ at subsequent doses.
- Malignancy: was observed in clinical studies.
Chest X-ray: Seldom diagnostic but valuable to
exclude alternative diagnoses and establish
presence of significant comorbidities.
Diffusing Capacity: to characterize severity.
Arterial Blood Gases: in advanced cases.
Alpha-1 Antitrypsin Level: required when:
• COPD develops under 45.
• COPD develops in non- smoker.
• Strong family history of COPD.
N: > 150 mg/dL . In disease: < 45 mg/dL
Reduction of exposures in the workplace.
Reduce indoor air pollution eg, from heating in poorly
Smoking cessation has the greatest capacity to improve
the natural history of COPD.
Pharmacologic Treatment of
• Inhaled bronchodilators (mainly long acting, LABDs) should be given
on a regular basis to ↓ resting and dynamic hyperinflation and prevent
or reduce symptoms.
• Use of SABDs on regular basis is not generally recommended, except
for patients with only occasional dyspnoea.
• LABA use does not preclude additional benefit from as needed SABA.
• SE of Beta Agonists (tend to ↓ over time: tachyphylaxis)
o Sinus tachycardia → palpitations.
o ↑ myocardial oxygen consumption
They may precipitate myocardial ischemia and decompensation,
particulary in presence of pre-existing coronary heart disease.
o Tremors (exaggerating the senile tremor).
o Hypokalemia (may be intentionally used to treat hyperkalaemia).
• They have a small advantage over beta agonists (contrary
to the situation in BA). (Why? Better response and more
favorable adverse effect profile noting the hazards of beta
agonists in middle aged and elderly people with pre-
existing heart disease).
• SAMA are better than SABA for immediate relief.
• LAMA are better than LABA for reduction of exacerbation
• Side Effects
o Dryness of mouth (main SE).
o Difficult micturition (particularly in presence of prostatic
o ↑ Intra-ocular pressure → may precipitate acute angle closure
glaucoma if given by face mask due to direct contact with the eye.
• Not recommended unless other LABDs are unavailable.
• Mechanism of Benefit controversial:
o Non- selective inhibition of phosphodiesterase → ↑ cAMP which
o Improved respiratory muscle function (? 1ry or 2ry to ↓ hyperinflation).
o Respiratory stimulant.
o Mild diuretic.
Adverse Effects: dose related
Therapeutic window is narrow.
Most of the benefit occurs near the toxic doses.
- Tachyarrhythmias: atrial tachycardia or fibrillation, ventricular tachycrdia or
fibrillation (last 2 rapidly fatal)
- Tremors, convulsions: even grand mal convulsions irrespective of prior
- Insomnia, headache.
- Nausea, vomiting, heart burn.
Mucolytics: Only in patients with viscid sputum; overall benefits
are very small.
Antitussives: Not recommended.
Macrolide Antibiotics: Decrease exacerbation rate, possibly due to
both antibacterial and immune-modulating action.
Combinations of Bronchodilators
• Combination of SABA/SAMA is superior to either medication alone.
• Combination of LABA/LAMA ↓ exacerbation rate to a greater extent
Long term monotherapy with ICS is generally not recommended, but it
may be considered in association with LABA for patients with a history
of exacerbation despite appropriate treatment with LABA.
Alpha-1 antitrypsin augmentation (replacement) therapy:
• The only specific therapy for
1 antitrypsin deficiency.
• Prepared from pooled plasma of
• Given as weekly IV infusion (60
• Not well tolerated (fever, chills,
flu like symptoms.
• Very expensive.
Non-Pharmacologic Treatment of
• Intermittent domiciliary oxygen ↑ survival in patients with
severe resting hypoxemia.
• It aims to keep SaO2 > 90%.
• Caution: may ↑ CO2 due to reduction of ventilatory drive
caused by hpoxemia.
Bullectomy and Lung volume reduction surgery
• Exacerbations are acute episodes of worsening
symptoms and airway obstruction that require additional
• Exacerbation contribute to disease progression,
especially if recovery from exacerbation is slow.
• Frequent exacerbations: having > 2 exacerbations/year.
The best predictor for having frequent exacerbations is the
number of previous exacerbations.
o Mild: treated with SABA, SAMA only (SABDs).
o Moderate: Treated with SABDs + antibiotics and/or
o Severe: requires hospital care.
• DD: comorbid events as acute coronary syndrome, and
worsening heart failure.
o ↑ Dose and/or frequency of SABDs.
o Combine SABAs and SAMAs.
o Consider LABDs when the pt becomes stable.
o Use spacers or nebulizers as needed.
o OCS (eg, Prednisone 40 mg once daily) may be used
for no more than 5 – 7 days.
o Antibiotics may be used if signs of bacterial infection
are present (sputum ↑ in amount and purulence).
Methyxanthines are not recommended due to ↑ risk profile.
o O2 Therapy: targeting SaO2 88 – 92%.
COPD and Comorbidities
• Lung Cancer is frequently seen in COPD and is a main
cause of death.
• Hypertension is the most frequently occurring
comorbidity with COPD. There is no evidence that
hypertension should be treated differently in presence of
COPD, apart from avoidance of non- cardioselective beta
• Obstructive Sleep Apnoea → overlap syndrome →
more severe and more prolonged sleep time hypoxia and
hypercapnoea → worse prognosis.
Cardiovascular Disease with COPD
Heart Failure Atrial Fibrillation
CVD is commonly associated with COPD.
Any one of these conditions can be a cause or a
consequence of the other. Any can cause worsening
• Although all beta agonists and muscarinic antagonists may
potentially precipitate AF or make rate control difficult, it seems that
the risk is significant only with SABA.
• Theophylline should not be used in COPD exacerbations as it may
precipitate AF and make control of ventricular rate difficult.
• Treatment with beta blockers improves survival in heart failure.
However, beta blockers are often not prescribed in COPD patients
despite available evidence showing that their use in COPD is safe.
• Selective beta 1 (cardioselective) agents should be preferred.
Cardioselective (Beta 1)
Propranolol amp 1 mg, tab 10, 40 mg Inderal
Atenolol tab 50, 100 mg Tenormin
Metoprolol tab 50, 100 mg Blokium
Bisoprolol tab 2.5, 5, 10 mg Concor
α, β Blocker Carvedilol tab 6.25, 25 mg Dilatrend