This ppt gives information about the introduction to asthma disease its causes, pathophysiology and classification of antiasthmetic drugs with its stucture , the ppt is made for basic knowledge of antiasthemetic drugs on medicinal chemistry point of veiw for B. pharmacy students.

1. ANTIASTHAMATICS
BY: PRIYA SHUKLA
DRUG ACTINGON RESPIRATORYTRACT

2. INTRODUCTION:
 The term asthma is derives from the greek
word aazein meaning to exhale with open
mouth.( Difficulty in breathing)
 Asthma is a chronic inflammatory allergic
disease , the patients suffer with reversible
episodes of airways obstruction due to
bronchial hyper responsiveness.
 In the early (acute)phase there are smooth
muscle spasm and excessive broncial
secretion of mucus.

3.  In the late (chronic or delayed) phase,
inflamation continues accompaines by
fibrosis oedema and necrosis of broncial
epithelial cell.

4. SYMPTOMS:
 Symptoms of asthma are breathlessness,
wheezing, cough and cheast tightness with
worsening of these symptoms at night.
 In the acute asthma there are rapid
respiratory rate and tachycardia.
 The majority of patients suffer with atopic
extrinsic asthma, which is associated with
expossure to specific allergen( pollen or
house dust, etc).

5.  In nonatopic extrinsic asthma the attack may be
stimulated with some non specific stimulus ,Ex
chemical irritants, In such cases IgG and Ig
antibodies circulate in the blood but are not
attach to the mast cell or basophills.
 Neutrophils destroy these antigen- antibody
complex as a result, the liberated lysosomal
enzymes can digest the remaining
mucoprotiens.
 Many patients have no identifiable external
precipitating or immunological basis for
asthamatic attack this can be described as
intrinsic asthma.

6.  Extrinsic asthma is episodic and less prone to
status asthmaticus.
 Status asthmatics is a sever acute asthma,
which is a life threatening condition involving
exhaustion, cynosis, bradycardia,
hypotension, dehydratin and metabolic
acidosis.

7. [PATHOPHYSIOLOGY OF ASTHMA
 Antigen (pollen and house dustmites) sensitive
patients by eliciting the production of IgE type of
antibodies.
 They become attach to mast cells of nasal or
bronchial tissues and basophils.
 On re exposure with same antigen, reulting
antigent- antibody reaction in the early phase
cause degranulation of lung mast cells and
releasing powerfull bronchoconstrictors
histamine, -HT, PGD2 AND Cysteinyl
leucotrienes( LTB4, LTC4, LTD4).

8.  Lungs mast cells also release Ils( IL-4, IL-5 &
IL-13) in the late phase of asthma, these
mediator activate inflammatory cells,
eosinophils, basophils, alveolar,
macrophases) which also release LTs & ILs .
 Other mediators of inflammation in delayed
phase are adenosine, neuropeptidases, etc.

9. Why asthma makes hard to
breath:
 In an asthamatic person the broncial tubes
are tighten and thicken and the air passage
become inflammes and mucuos filled,
making it difficult for air to move, which
make patients hard to breath.

10. Classification of
Antiasthamatic drugs:
 The drugs are classified into following
classes:
I . BRONCHODILATORS
a. Selective ß2- agonists
b. Nonselective ß-agonist
c. M- cholinolytics
II . ANTI INFLAMMATORY AGENTS
2. Mast cell stabilizers
3. Glucocorticoids

11. 4. Leukotriene modulators
5. Monoclonal anti-IgE antibody
1. BRONCHODILATORS:
a. Selective ß2 – Agonists:
MOA:
Beta- 2 receptor/ G- protein complex increase c-
AMP production.
Increase c-AMP activate proteinkinase A(PKA)
PKA phosphorylates myosin light chain
kinase(MLCK).
Phosphorylated MLCK was decreased affinity for
calcium- calmodium complex.

12.  Less phosphorylation of myosin light chain
decrease activity of smooth muscle actin/
myocin & cause bronchodialation.
 Examples:
1. Salbutalol

13. 2. CLENBUTEROL:

14. 3. FENOTEROL

15. 4. INDUCATEROL:

16. 5. SALMETEROL:

17. 6. TERABUTALINE:

18.  b. Nonselective ß- agonists:
 examples:
1. Epinephrine

19. 2. ISOPRENALINE

20. 3. EPHEDRINE:

21. 4. ORCIPRENALINE:

22. c. M-CHOLINOLYTICS:
Examples:
1. Ipratropium bromide

23. 2. TIOTROPIUM:

24. 3. OXITROPIUM:

25.  MOA:Atropinic drugs cause bronciodilation
by blocking cholinergic constrictor tone, act
primarily in large airways.
4. Methyl xanthines derivatives:
Example:
Theophylline

26. 2. AMINOPHYLLINE:

27. (a) Inhibit phosphodiasterase-III & IV
The two specific isoenzymes responsible for
degradation of Camp.
(b) Block the adenosine-1- receptors on airway
musle and adenosine-3 receptors, present
on mast cells

28.  MAST CELL STABILISERS:
 Example: - sodium cromoglucose

29. 2. KETOTIFEN(H1
antihistaminic mast cell
stabilizer):

30. 3. NEDOCROMIS:

31. Cromolyn works by preventing the release of
mediators that would normally attract
inflammatory cell & becoz it stabilies the
inflammatory cells.

32.  3. GLUCOCORTICOIDS (GCS)
Provides long term stabilization of the symptoms
due to their Anti-inflammatory effects GCS
inhibit the release of PG 4 LTs thus block smooth
muscle contraction vascular permeability airway
mucus secretion.
GCS produces eiosinopenia which prevents
cytotoxicity of the merditors released from
eosinophills.
The anti-inflammatory actions of GCS are
mediated by simulation of synthesis of lipocortin
which inhibits pathway for production of PGs,
LTs & PAF.
This mediators normally increase vascular
permeability & subsequent change including
odema leucocyte and fibrin deposition.

33. Examples:
Prednisone

34. 2. METHYLPREDNISOLONE:

35. 3. BETAMETHASONE:

36. 4. BECLOMETHASONE:

37. 5. BADESONIDE:

38. 6. FLUTICUSONE:

39. 7. TRIAMEINOLONE:

40. 4. LEUKOTRIENE MODULATORS:
 Metabolism of archidonic acid via 5-lipoxygenase
pathway yields the cysteinye LTs-C4, D4 & E4
which activate cysteinyl leukotriene receptors to
cause bronchoconstriction, stimulate mucus
sence & increase capillary permeability leading
to pulmonary oedema.
 Zeleuton inhibit the 5- lipoxygenase &block
synthesis of LTs.
 Zarfiralakust , Monolakust and pranulakust block

41.  Cystiene LT- receptors and used with inhales
GCS in poorly respond asthmatic patient.

42. Ex: ZILEATONE:

43. 2. MONTELEUCASE:

44. 5. MONOCLONAL ANTI-IgE
ANTIBODY:
 Ex: Omalizumab is a recombinent humanized
monoclone antibody
1. It inhibit the binding of IgE to mast cell
2. It inhibit the binding of IgE to basophills
3. It inhibit activation of IgE to prevent mast
cell degranulation.