6. Salbutamol (Albuterol):
highly selective β2 agonist
not suitable for round-the-clock prophylaxis
Pharmacokinetic & pharmacodynamics:
Oral bioavailability is 50%
Duration of action: 4-6 hrs(oral), 2-3 hrs(inhalational)
Oral therapy reserved for patients unable to use inhalers correctly/adjunct
drug for severe asthma
8. Terbutaline:
Similar to salbutamol
Should not be used on any regular schedule
bronchial hyperreactivity: may even worsen
diminished responsiveness seen after long-term use
Restricted to symptomatic relief of wheezing
9. Bambuterol:
Biscarbamate ester prodrug of terbutaline
hydrolysed in plasma and lungs by pseudocholinesterase - release the
active drug over 24 hours
Reversible inhibition of pseudocholinesterase
It is indicated in nocturnal and chronic asthma
10. Salmeterol:
Long acting selective β2 agonist(more lipophilic)
Slow onset of action
Inhalation on a twice daily schedule for
maintenance therapy and for
nocturnal asthma
Concurrent inhaled steroid:
Reduces risk of life-threatening asthma attacks
11. COPD:
• superior to short-acting β2 agonists
• equivalent to inhaled anticholinergics
• prevent expiratory closure of peripheral airways and
• abolish the reversible component of airway obstruction
12. Formoterol:
faster onset of action
used on a regular morning-evening schedule for round-the-clock
bronchodilatation
Ephedrine:
has α + β1 + β2 actions
mild slowly developing bronchodilatation lasting for 3–5 hours
not preferred now
low efficacy
frequent side effects
13. PHOSPHODIESTERASE INHIBITORS:
Methyl xanthines:
Theophyline and its compounds
Mechanism of action:
1. Inhibition of phosphodiesterase (PDE)
2. Blockade of adenosine receptors
3. Interleukin-10 release
4. Effects on gene transcription
5. Effects on apoptosis
6. Histone deacetylase activation
15. Theophylline:
Pharmacokinetics:
Well absorbed orally
Crosses placenta & Secreted in milk
V = 0.5 l/kg
50% plasma protein bound
metabolized in liver by demethylation and oxidation(CYP1A2)
t½ in adults is 7–12 hours(3–5 hours in children)
Saturable kinetics
Dose reduction needed: age>60yrs, CHF, pneumonia, liver failure
18. Uses:
Bronchial asthma and COPD:
Benefits by
• bronchodilatation
• by decreasing release of inflammatory mediators
• promoting eosinophil apoptosis
• Improved mucociliary clearance
• stimulation of respiratory drive and
• Augmentation of diaphragmatic contractility
But rarely used now:
• narrow margin of safety
• limited efficacy
• 3rd line or alternative/adjuvant
21. Ipratropium bromide:
short acting(4-6hr)
Inferior to β2 sympathomimetics in asthma but superior in:
asthmatic bronchitis,
COPD(drug of choice)
and psychogenic asthma
Regular prophylactic use(2–4 puffs 6 hourly)
Additive with β2 agonist(combination used in severe asthma)
Tiotropium bromide:
longer acting(24hrs)
More effective in severe COPD (FEV1<50%)
24. INHALED STEROIDS:
high topical and low systemic activity
indicated in all cases of persistent asthma
Started with 100–200 μg BD
titrated upward every 3–5 days(max-400 μg QID)
Have no role in: acute attack & status
Peak effect in 4-7days
COPD:
Not much effective
High dose in advanced COPD
26. Beclomethasone dipropionate:
pMDI & rotacaps
Intranasal spray (50 μg in each nostril BD–TDS): perennial rhinitis
Budesonide:
high topical: systemic activity ratio(high first pass metabolism)
preferred in more severe cases
Fluticasone propionate:
high potency(double of beclomethasone)
Longer duration and negligible oral bioavailability
inhalational dose is 100–250 μg BD (max 1000 μg/day).
27. Flunisolide:
seasonal and perennial rhinitis
Ciclesonide:
a prodrug that is cleaved by esterases in the bronchial epithelium to
release the active moiety
oral bioavailability is <1%
extensively bound to plasma proteins in circulation
28. SYSTEMIC STEROID THERAPY:
1. Severe chronic asthma:
prednisolone 20-60mg/day
dose reduction afeter 1-2 wk attempted
2. Status asthmaticus:
high dose of a rapidly acting i.v. glucocorticoid
generally act in 6-24 hrs
shift to oral for 5-7 days & then inhalational
3. COPD:
short course (1–3 week) of oral glucocorticoid for exacerbation
30. Montelukast and Zafirlukast:
Competitively antagonize cysLT1 receptor
There are ‘responders’ and ‘non responders’ to anti-LT therapy
prophylactic therapy - mild-to-moderate asthma as alternatives to
inhaled glucocorticoids
In severe asthma - additive effect with inhaled steroids
no value in COPD
Side effects:
Headache and rashes
Eosinophilia and neuropathy
Churg-Strauss syndrome
33. MAST CELL STABILIZERS:
Sodium cromoglycate: (Cromolyn sodium)
Inhibits degranulation of mast cells
May involve a delayed Cl¯ channel in the membrane of these cells
Not effective in acute attack
Pharmacokinetics:
not absorbed orally
administered as an aerosol through metered dose inhaler
1 mg per dose: 2 puffs 4 times a day
34. Uses:
1.Bronchial asthma:
prophylactic in mild-to-moderate asthma
Beneficial in extrinsic (atopic) and exercise-induced asthma,
especially in younger patients
Therapeutic benefit develops slowly
Less effective than steroids & seldom used now
2.Allergic rhinitis
3.Allergic conjunctivitis
35. ANTI-IgE ANTIBODY:
Omalizumab:
Humanized monoclonal antibody against IgE
Administered subcutaneously
In severe extrinsic asthma: reduce exacerbations and steroid
requirement
No benefit: nonallergic asthma
very expensive
reserved for resistant asthma with positive skin tests or raised IgE
levels
39. Characteristics:
Acute exacerbation of asthmatic attack which can be life threatening.
Symptoms like:
increasing chest tightness
Wheezing
Dyspnea
Increased ventilation
Hyperinflation
Tachycardia
Poorly relieved by inhalers
40. Management:
i. Hydrocortisone hemisuccinate 100 mg i.v. stat, followed by 100–
200 mg 4–8 hourly infusion(may take upto 6 hours to act)
ii. Nebulized salbutamol (2.5–5 mg) + ipratropium bromide (0.5 mg)
intermittent inhalations driven by O2
iii. humidified oxygen inhalation
iv. Salbutamol/terbutaline 0.4 mg i.m./s.c. may be added
v. Intubation and mechanical ventilation, if needed.
vi. intensive antibiotic therapy for chest infection
vii. Saline + sod. bicarbonate/lactate infusion for dehydration and
acidosis management