Asthma is a chronic lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath, and coughing. The coughing often occurs at night or early in the morning

1. ASTHMA
PREPEARED BY ZUHAIB AKHTAR BALOCH
A PHARM – D STUDENT OF 5TH SEMSTER
IN UNIVERSITY OF BALOCHISTAN SUB CAMPUS MASTUNG
FOR ANY QUESTION YOU CAN CONTACT ME ON INSTAGRAM :- ZUAIB_BALOC

2. ASTHMA
Asthma comes from a greek word for (panting) which makes sense because it
causes
Chronic inflammation of the airway , making them narrow & more difficult to
breath enough
Asthma :- A condition in which your airways narrow , swell & produce extra mucus
which can make breathing difficult and trigger coughing, wheezing and shortness
of breath
Or
Asthma :- A disease characterized by airway inflammation & episodic reversible of
bronchiospam with severe shortness of breath .

3. THERE ARE TWO TYPES OF ASTHMA
ATOPIC AND NON-ATOPIC
ATOPIC ASTHMA
• known as Extrinsic asthma
(means it’s triggered by the environment like
Dust , mites , molds , pollen , fur and e.t.c)
• It’s the most common type
• It’s caused by inflammation mediated by
systemic IgE production
• It’s also know as Allergic asthma
NON-ATOPIC ASTHMA
• Know as Intrinsic Asthma
(Means it’s trigged by natural action like vagal
reflex , cold , NSAIDs , Stress viral infections and
e.t.c)
• It’s not common type
• It’s caused by inflammation mediated by local
IgE production
• Also known as non Allergic asthma

4. CAUSE OF ASTHMA
It’s caused by something in the environment which causes immune cell to generate
inflammation in the lungs which make them even more narrow & potentially be
life-threating this environmental substance could be any thing we will discuss it on
next page which substance triggers Asthma .

5. CAUSES OR TRIGGERS OF ASTHMA
Asthma triggers are different from person to peraon
They can include
1. Airborne – Substances (Pollen , dust , mites , mold spores , e.t.c)
2. Respiratory infection (common cold)
3. Physical activity (exercise)
4. Cold air
5. Air pollutants (smoke of cigerette , cars , factories , burning of plastic e.t.c)
6. Medications like (Beta blockers , aspirin , iburofen , and naproxen)
7. Strong emotions & stress
8. Food (Sulfites and preservatives added to some types of foods and beverages, including shrimp, dried fruit, processed potatoes, beer and
wine)
9. Genetic

7. PATHOPHYSIOLOGY OF ASTHMA
Trigger particles (environmental particles) are picked up by Dendritic cells which
present them to (Th2) cell which then produces cytokines (IL4 & IL5)
IL4 :- leads the production of IgE antibodies which coat Mast cells & stimulate
them to release Granules containing things like (histamine , prostaglandin ,
leukotriens)
IL5 :- leads to activate eosinophils which promotes an immune response by
releasing more cytokines and leukotriens .
As we can see igE antibodies are being produced so this is know as the example
of type 1 hypersenstivity .

10. Early on minutes - after the exposures of Allergens the Smooth muscles around the
bronchioles start to spasm and there’s an increased of mucus secretion which starts to
narrow the airway making it difficult to breath . This is why asthma is considered to be
a type of obstructive pulmonary disease . There’s also an Increase in vascular
permeability & recruitment of additional immune cells from the blood . So a Few
hours after the exposures , these immune cells particularly eosinophils release
chemical mediators that physically damage the endothelium of the lungs .

12. ASTHMAIC BRONCHIALS
In asthmaic bronchial the lumen inside is much narrower because in asthmaic
bronchial there’s increase in mucus production so there’s an increase as well as
Goblet cells which secrets mucus also there’s increase in esonophils in the mucus
and tissue . With in lamina propria we find An increase number of mast cell which
than secretes histamine , prostaglandins and leukotriens . We also find increse of
other cells inner side of limina proparia like neutrophils during inflammation as
well as the T helper cells . In next picture you will find out smooth muscles cells are
increased in size due to the constrictions occurred .

15. SYMPTOMS OF ASTHMA
• Wheezing :- Wheezing occurs when the small airways of the lungs become
narrow or constricted. This makes it difficult to breathe, and can cause a whistling
sound when breathing out .
• Cough :- In asthma the cough is nonproductive cough is a dry cough . It’s a
response to an irritant that forces the bronchial tubes to spasm (or constrict).
Swelling (inflammation) and constriction of the airways, which prompts this type of
nonproductive cough, characterize asthma.
• Shortness of breath :- Shortness of breath caused by allergies or other
common asthma triggers

16. • Trachycardia :- In the case of asthma, your lung volume, capacities, and
flow rates are compromised and can affect your exercise. This could indirectly affect
your heart rate because asthma might cause a lower amount of oxygen in the blood
stream, so the heart cardiac output will be higher to combat this
• Difficulty breathing :- In asthma airways are narrowed (skinny), so less air can move
in and out of the lungs So during an asthma attack, air gets trapped inside the lungs
making it harder and harder to breathe .
• Pale & wet skin :- Paleness itself is essentially caused by a decreased level of
oxyhaemoglobin within the skin or mucus membranes. The lack of this compound will
drain the color from the skin and cause your appearance to appear pale .

17. • Chest tightness :- If you have asthma, your immune system can cause your
airways to become inflamed and swollen when you're around certain irritants.
This can lead to chest tightness, pressure, or pain.
• Dyspnea :- when you couldn’t breathe in enough air, you’ve experienced a
condition known medically as dyspnea it happens when you have trouble
breathing in enough oxygen to meet your body’s increased demand due to
narrow airways of lung

19. BRONCHIODILATORS
(MODE OF ACTION)
• These drugs stimulates Beta 2 receptors which are Gs linked receptors . This causes activation
of the enzyme Adenyl cyclase and therefore increased conversion of ATP into cAMP (which is
the major second messenger of beta Receptor activation)
• cAMP then produces relaxation of smooth muscles of the bronchi (Bronchiodilation) . This
involves phosphorylation of myosin light chain kinase to an inactive form causing inhibition of
contraction of smooth muscle .
• Beta receptor activation also inhibit release of bronchoconstricting and inflammtory mediators
from mast cells .
• They may also inhibit microvascular leakage .
• Increase mucociliary transport by increasing cikiary muscles .

20. • Inhibit vagal tone (minor effect)
• Inhibit phospholipase 2 , the enzyme that liberates arachidonic acid , the source
of inflammatory products like prostaglandins and leukotrienes (minor effect)

22. PHARMACOKINETICS OF BRONCHIODILATORS
Route of administration
• Inhalational route :- most commonly used : rapid action : less Adverse
effects
• Oral :- orally in tablets form including Sr tablets - (Modified-release dosage
and its variants are mechanisms used in tablets (pills) and capsules to dissolve a
drug over time in order to be released slower and steadier into the bloodstream)
Onset of action is Slow produce bronchiodilation after about 30minutes .
• Subcutaneous :- onset of action is rapid
• Intravenous :- Onset of action is rapid Occuring in a few minutes .

23. • Metabolism :- When swallowed may undergo conjugation in
Gut as well as in Liver .
• Excretion :- Relatively small quantities of these drugs are
excreted unchanged by the kidney & dosage modification Is
unnecessary in renal insufficuency .
• Contraindication :- slightly Penetrate the blood brain barrier
And also cross the placenta so that oral medication is perhaps
better avoided in pragnancy

24. SIDE EFFECTS
• Nausea and vomiting
• Diarrhoea & Myocardial ischemia
• Palpitations & Dry mouth
• a rapid heartbeat (tachycardia)
• an irregular heartbeat (arrhythmia)
• Headaches , anxiety & Nervousness
• problems sleeping (insomnia)

25. CORTICOSTEROIDS
(MODE OF ACTION)
• Coticosteroids reduce airway inflammation thereby decreasing mucus secretion & reducing
bronchial activity .
• The use of oral or parentral corticosteroids reduces hospitalization & imprives lungs function , can
lead to control of airway inflammation & prevention of relapses .
• Systemic steroids are slow to take effects (6 to 12) hours because they depends on complex cellular
mechanism (Genomic effects)
• Corticosteroids have no direct effect on the airway smooth muscles , rather inhaled glucocorticoids
decrease the number & activity of cell involved in airway inflammation such as macrophages ,
eosinophils & T-lymphocytes . Glucocorticoids are drugs of 1st choice in patient with moderate to
severe asthma
• No other medications are as effective as inhaled corticosteroids in the long term control of asthma
in children and adults .

28. PHARMACOKINETICS
Route of administration
. Oral :- dosage forms (elixir, oral solution, tablets) onset of action is slow
• Parentral route of administration is also used
• Inhalation form :- relief of acute attack is rapid

29. • Absorption :- All are rapidly cleared from the body but they show varying levels of
oral bioavailability and more importantly variation in the rate of absorption after
inhalation .
• Metabolism :- Corticosteroid metabolism occurs primarily in the liver.
• Excretion :- Cortisol excretion in urine is relatively low, 100 μg/d, primarily because 80
to 90% of filtered cortisol is reabsorbed, mostly from the distal tubule of the kidney.

30. SIDE EFFECTS
1. Oropharyngeal candidiasis
2. Dysphonia
3. Hoarseness of voice
4. Osteoporosis & increased vulnerability to infection,
5. Hyperglycemia & diabeties
6. Hypertension & weight gain
7. Peptic ulcer
8. Features of cushing’s syndrometic
9. Inhaled glucocorticoide can slow growtg rate in children
10. Cataracts and glaucoma (eye disorders),
11. thinning of the skin,

31. MAST CELLS STABLIZERS
• Mast cell stabilizers work to prevent allergy cells called mast cells from breaking
open and releasing chemicals that help cause inflammation.
• Mast cell stabilizers are not rescue medicines.
• They work slowly over time, taking two to six weeks to become effective.
• Mast cell stabilizers come in metered dose inhalers and in a solution for
nebulizers.
• They must be taken two to four times a day to work.

32. • Cromolyn & Nedocromil are effective prophylatic anti-nfammatory agents.
• however they are not useful in managing an acute asthmatic attack because
they are not direct bronchodilators. .
• These agents can block the initiation of unmed‘ate & delayed asthmatic
reactions.
• They appear to stabilize the mast cell membrane and to inhibit release of
inflammatory mediators

33. MAST CELL STABLIZER
(PHARMACODYNAMICS)
• Cause Alteration in function of delayed chloride ion Channels in the cell
membranes , thus inhibiting cellular activation .
• Airway nerve & irritant receptors : decreased neuronal reflexes — inhibition of
cough .
• Mast cells : inhibition of the early response to antigen challenge ; thus decreased
release of bronchospasmic and inflammatory mediators substances .
• Eosinophils : inhibition of the inflammatory response to inhalation of allergens ;
decreased influx of eosinophils into the lungs .

34. PHARMACOKINETICS
• Cromolyn and nedocromil are poorly absorbed after oral administration (0.5%)
a. after inhalation (5%).
• The absorbed portion is rapidly eliminated unchanged in urine & bile.

35. USES OF MAST CELL STABLIZER
• Effective only When inhaled directly into the airways ; only used as prophylaxis
and only used by route of Inhalatuon .
• Used prophylactically in asthma (seasonal or non–seasonal)
• Used to prevent seasonal increases in bronchial reactivity in patients with asthma
& COPD
• Used to prevent exercise induced asthma

36. SIDE EFFECTS OF MAST CELL STABILIZER
1. Bitter taste
2. Throat irritation
3. Cough
4. Mouth dryness
5. Chest tightness
6. Wheezing
7. Rarely dermatitis
8. Myosits
9. Gastroenteritis
10. Anaphylaxis

37. MECHANISM OF ACTION AND USE OF ANTI-IGE
ANTIBODIES
OMALIZUMAB
• New approach to treatment of asthma that exploits the advances in molecular
biology to target lgE antibodies .
Mode of Action :- A monoclonal antibody is selected that targets that
portion of lgE that binds to its receptors on mast cells & other inflammatory cells .
• This anti-lgE antibody inhibits the binding of lgE to mast cells but does not
activate lgE already bound to these cells & thus does not provoke mast cell
degranulation .
• They may also inhibit lgE synthesis by B Lymphocytes .

38. Action :- it has shown to decrease plasma lgE levels to undetectable levels over 10 weeks &
reduce the magnitude of both the early & late bronchospastic response to antigen challenge .
Uses :-
• Bronchial asthma, especially those with a clear environmental antigen precipitating factor .
• Also used in Patients with Seasonal Allergic Rhinitis to improve nasal & conjunctival symptoms
.
• Reduces the frequency and severity of asthma attacks .
• Decreases doses/requirement of corticosteroids .
• Most useful in resistant cases in patients with increased frequency & severity of attacks and
those needing high doses of corticosteroids .