This document discusses the roles of anticholinergics, leukotriene antagonists, and mast cell stabilizers in the treatment of bronchial asthma. It describes the mechanisms of action and side effects of different drugs in each class, including ipratropium bromide, montelukast, zafirlukast, sodium cromoglycate, and ketotifen. These drugs work through various pathways to reduce bronchospasm, inflammation, and symptoms of asthma. Common side effects are mild and include headaches, rashes, sedation, and dry mouth.

1. Role Of Anticholinergics,
leukotriene Antagonists and
Mast Cell Stabilizer...In
Bronchial Asthma ?
BY
M. AKHILA
INDU

2. ANTICHOLINERGICS-IPRATROPIUM
BROMIDE AND TIATROPIUM
BROMIDE.
 Distinct muscarinic receptors exist within the airways re M1 and M3
receptors.
 M1-presents in peribronchial ganglion cells where the preganglionic
nerves transmit to the postganglionic nerves.
 M3 are present on smooth muscle larger airways .
 Muscarinic receptor activation of these M3 receptors
 Intracellular cAMP levels contraction of airway
Smooth muscle bronchoconstriction.
 Postganglionic fibers supply the smooth muscle and sub mucosal glands of
the airways as well as the vascular structures.
 Motor nerves derived from the vagus form ganglia predominate in the
large and medium-sized airways.
 Atropinic drugs block these cholinergic innervations and bringd about
bronchodiatation.

3. ANTICHOLINERGICS-CONTD.
 Less efficacious than sympathomimetics.
 COPD, asthmatic bronchitis, psychogenic asthma-respond
better.
 Drug of choice in COPD.
 Slower response-for prophylaxis (2- 4 puffs 6 hrly).
 IB + sympathomimetics = marked longer lasting
bronchodilatation.
 Nebulized IB and Salbutamol-refactory asthma.

4. LEUKOTRIENE ANTAGONISTS
:DRUGS
 There are mainly two leukotriene anatagonist drugs,
they are:
 1. montelukast
 2.zafirlukast
 Both these two drugs are within the chemical family
of cysteinyl leukotriene antagonists

5. LEUKOTRIENE ANTAGONISTS :
PHARMACOKINETICS
 Both the drugs are well absorbed orally.
 They bond withj plasma very highly, so the volume of
distribution is very low.
 There are extensively metabolized by CYP2C9 and
CYP3A4 isoenzymes in liver.
 Plasma half life : montelukast :3-6 hours.
zafirlukast :8-12 hours.

6. LEUKOTRIENE ANTAGONISTS:
mechanism of action
 Both the drugs montelukast and zafirlukast act similarly.
 They competitively inhibit cysteinyl leukotriene receptors and causes :
 1.Bronchodilation.
 2.suppression of bronchial inflammation.
 3.Reduced sputum eosinophil count.
 They are used for prophylactic therapy of mild to moderate asthma as
alternatives of inhaled glucocoeticoids.
 In severe asthma they may be used to reduce dosage of steroids.
 They are not to be used for terminating episodes of asthmatic attack.
 They are effective in treatment of aspirin induced asthma.

7. LEUKOTRIENE ANTAGONISTS:SIDE
EFFECTS
 Montelukast and zafirlukast are very safe drugs.
 They produce very few side effects like headache and
rashes.
 Very few cases of churg-strauss syndrome (vasculitis
with eosinophilia) has been reported.

8. MAST CELL STABILIZERS
:DRUGS
Sodium cromoglycate.
Kitotifen.

9. MAST CELL STABILIZERS :
PHARMACOKINETICS
 1.SODIUM CROMOGLYCATE :
 Sodium cromoglycate is not absorbed orally.
 It is absorbed as an aerosol through metered dose inhaler.
 Only a small fraction is absorbed systemically.
 Rest of the portion is rapidly excreted unchanged in urine and bile.
 2.Kitotifen :
 It is absorbed orally.
 Bioavailability is 50% due to first pass metabolism.
 It is largely metabolized.
 Plasma half life is 20-22 hours.

10. MAST CELL STABILIZERS :mechanism
of action
 These drugs inhibit degranulation of mast cells.
 Release of mediators like Histamine, LT<PAF<IL is inhibited.
 This action may include delayed CI channel.
 Chemo taxis of inflammatory cells is inhibited.
 Bronchial hyperactivity is reduced.
 Bronchospan due to various stimuli (allergens, irritants, cold
air and ecercise) is prevented.
 It can’t be used to prevent attacks of asthma because it does
not affect the constrictor action of histamine.

11. MAST CELL STABILIZERS
:uses
 Sodium cromoglycate :
 1.Bronchial asthma : it is used as a long term prophylactic in
mild to moderate asthma. Decrease in frequency and severity
of attacks and improvement in lung function is more likely in
extrinsic asthma. Lasts 1-2 weeks after discontinuing.
 2.Allergic rhinitis : Sodium cromoglycate is not a nasal
decongesant. But 4times daily use as a nasal spray can
produce symptomatic improvement in 4-6 weeks.
 3.Allergic conjunctivitis : Regular use as eye drops is beneficial
in some chronic uses.

12. MAST CELL STABILIZERS
:uses
 KTOTIFEN :
 1.After 6-12 weeks of use, it reduces symptoms in
about 50% patients of bronchial asthma.
 But lung function improvement is marginal.
 It also produces symptomatic relief in patients with
Atopic dermatitis, Perennial rhinitis, Conjunctivitis,
Urticaria and food allergy. Thus, it is essentially
indicated in patients with multiple disorders.

13. MAST CELL STABILIZERS :Adverse
effects
 Sodium cromoglycate : It is poorly water soluble, so poorly
absorbed and systemic toxicity is minimal. Rare side effects
are :
 Bronchospam.
 Throat irritation.
 Cough.
 Headache.
 Dizziness.
 Arthralgia.
 Rashes.
 Dysuria.

14. MAST CELL STABILIZERS :Adverse
effects
 Ketotifen : Generally this drug is well tolerated. Rare
side effects are:
 Sedation.
 Dry mouth.
 Dizziness.
 Nausea.
 Weight gain.

15. THAN Q