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White Blood Cells
White blood cells, or leukocytes, are cells of the immune system
defending the body against both infectious disease and foreign There
are 2 main types of Leukocytes:
• Granulocytes
• Agranulocytes
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Mast Cells
• Resides in tissues of airways and bronchial tubes
• Part of body’s immune system
• Produce cytokines to mount inflammatory response
• Histamine and Leukotriene are most common mast cell mediators
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INFLAMMATION
Inflammation is one of the first responses of the immune system to
infection/invasion.
It is characterized by
• Increased blood flow
• Increased temperature
• Redness
• Swelling
• Pain
• Loss of function
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Leukotriene
• Mast Cell Mediators
• Secreted from mast cell upon antigen-antibody exposure
• 1000 time more potent in inflammatory responses than histamine
• Converted into different analogs such as LTA4, LTB4, LTC4, LTD4.
• LTC4 and LTD4 are called Cysteinyl Leukotriene
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Histamine
• Histamine is a chemical released from allergic cells in the body such
as mast cells and basophils.
• When histamine is released by allergic cells in the nose and eyes, the
result is:
• Sneezing
• Runny nose
• Itchy eyes/nose/throat
• Nasal congestion
• Post-nasal drip
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Asthma
• Asthma is a disease that affects the breathing passages of the lungs (bronchioles).
• Asthma is caused by chronic inflammation of these passages. This makes the breathing
passages or airways highly sensitive to various "triggers."
• When the inflammation is "triggered" by any number of external and internal factors, the
passages swell and fill with mucus.
Muscles within the breathing passages contract (bronchospasm), causing even further
narrowing of the airways.
This narrowing makes it difficult for air to be breathed out (exhaled) from the lungs.
• This resistance to exhaling leads to the typical symptoms of an asthma attack.
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Classification of Asthma Symptoms
• Mild intermittent: This includes attacks no more than twice a week and
nighttime attacks no more than twice a month. Attacks last no more than a
few hours to days.
• Mild persistent: This includes attacks more than twice a week, but not
every day, and nighttime symptoms more than twice a month.
• Moderate persistent: This includes daily attacks and nighttime symptoms
more than once a week. More severe attacks occur at least twice a week
and may last for days.
• Severe persistent: This includes frequent severe attacks, continual daytime
symptoms, and frequent nighttime symptoms.
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Measurement of Asthma
• Spirometer: This device measures how much air you can exhale and
how forcefully you can breathe out. The test may be done before and
after you take inhaled medication.
• Peak flow meter: This is another way of measuring how forcefully you
can breathe out during an attack.
• Oximetry: A painless probe, called a pulse oximeter, will be placed on
your fingertip to measure the amount of oxygen in your bloodstream.
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Treatment
Controller medications:
• These are for long-term control of persistent asthma. They help to
reduce the inflammation in the lungs that underlies asthma attacks.
These are medication that are taken daily regardless of symptoms
• Montelukast
Rescue medications:
• These are for short-term control of asthma attacks, taken only when
an attack of asthma takes place -- for example, when you have an
infection in your respiratory tract.
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Allergy
• Allergy is a response of immune system to harmless foreign particles – antigens
• Allergy is one of four forms of hypersensitivity and is called type I (or immediate)
hypersensitivity.
• It is characterized by excessive activation of certain white blood cells called mast
cells and basophils by a type of antibody known as IgE, resulting in an extreme
inflammatory response.
• Common allergic reactions include eczema, hives, hay fever, asthma attacks, food
allergies, and reactions to the venom of stinging insects such as wasps and bees.
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Pathophysiology
• Allergen Exposure to IgE attachment of antigen with
mast cell Mast Cell Sensitization mast cell
degranulation Secretion of mast cell mediators such as
Histamine
• Histamine produce inflammatory responses
• Dilates the blood vessels
• Increase the permeability of blood vessels
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Symptoms
• Rhinorrhea
• Itchy nose
• Sore Throat
• Sneezing
• Redness of the eyes
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Montelukast
• Montelukast is a drug used as control and maintenance therapy for
asthma.
• It also relieves symptoms of seasonal allergic rhinitis (SAR).
• It’s a Leukotriene receptor antagonist (LRTA)
• It binds with Cysteinyl Leukotriene Receptor in the lung and bronchial
tubes thus blocks the action of LTD4 – Bronchial constriction, accumulation
of mucosa and infiltration of inflammatory cells in the air ways
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Mechanism of Action
• Montelukast is a Leukotriene Receptor Antagonist.
• It binds with CysLT1 receptor site on the mast cell thus block the
secretion of Leukotriene (LTD4).
• This blockage helps in relieving symptoms that were caused by
Leukotriene such as broncho constriction, obstruction in air ways and
infiltration of inflammatory cells into air ways.
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PK/PD
Mean Peak Plasma Concentration Cmax 667ng/ml
Mean Peak Plasma Concentration Tmax 3-4 hrs
Protien Binding 99%
Half Life 2.7-5.5 hrs
Metabolism Hepatic
Elimination 87% from Feaces
Montelukast PK/PD
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Dosage
• Adults and adolescents 15 years of age and older:
one 10-mg tablet a day
• Pediatric patients 6 to 14 years of age:
one 5-mg chewable tablet a day
• Pediatric patients 2 to 5 years of age:
one 4-mg chewable tablet a day
• Pediatric patients 12 to 23 months of age: one packet of 4-mg oral granules