chapter 7 Pharmacology

Lung inflammation can result from
inhalation of toxic substances

(cont’d) The resulting
mucosal edema
increased mucus production can be life-threatening because of
increases in airway resistance from swelling
decreasing ventilation leading to poor gas exchange

Inflammation occurs in response to a stimulus that causes release of
chemical mediators that travel to the site of injury

Major function of the body’s natural defense mechanism (immune system) is to
neutralize, destroy and eliminate foreign materials called ANTIGENS
*Accomplishes this through the ability of white blood cells to produce specific antibodies to combat foreign invasion

Antigens stimulate both
immune and inflammatory processes

Immune system has two functional units
humoral (circulating) immunity
cell mediated immunity

Humoral immunity or cell mediated immunity can respond to an
antigen and activate the white blood cells Lymphocytes as well as Macrophages

Humoral immune response involves activation of
B lymphocytes

cell-mediated immunity involves production of
T lymphocytes

B LYMPHOCYTES produces antigen-specific antibodies called
Immunoglobulins that act to remove/destroy antigen

T LYMPHOCYTES remove or destroy antigens directly or may act indirectly, with help from
macrophages and neutrophils

Most common immune system-produced antibody involved in allergic asthma and rhinitis is

Once IgE becomes exposed to an antigen,
it fixes itself to the surface of a mast cell membrane

Mast calls can be found
thoughout the body

Once antigen attaches to the mast cell, the mast cell becomes
sensitized and awaits re-exposure of antigen

Upon reexposure, an antigen-antibody reaction occurs, which consists of a cascade of
chemical mediators

Spilling from ruptured mast cell (degranulation)
Chemical mediators

Mediators released include

Represents a disease of chronic inflammation

Used to illustrate inflammatory response

Inflammatory response
is a needed body response
it’s only HYPERACTIVATION of this response can cause serious consequences

2 main types of asthma
allergic asthma
nonallergic asthma

Most people have an
allergic kind

Allergic kind caused by
EXTERNAL antigen such as

External antigens lend itself to treatment with
immunotherapy (allergy shots)

Allergy shots work because an allergic individual exposed to small doses of an antigen or allergen
produces antibodies that are specific to this antigen

Antibodies are sensitized and can recognize and fight the antigen when it

Allergy shots only used when
drug therapy is not effective for allergies (this is because immunotherapy treatment can be lengthy, with symptom relief not occurring until after at least 6 months of therapy)

Patients who receive allergy shots always have a risk of
(believed that too many mast cells become sensitized and subsequent chemical mediator release can be too great)

Nonallergic asthma is precipitated by
cold air

No immune response involved, but
mast cells still degranulate, which then can result in acute asthma attack

lessening the frequency and severity of attacks from either nonallergic or allergic asthma is accomplished by
Prophylactic antiasthmatic agents, which stabilizes/desensitize mast cells, thus preventing rupture and chemical mediator release

Prophylactic antiasthmatic agents known as
mast cell stabilizers

Inflammatory response related to an asthmatic attack and mast cell degranulation have 2 distinct phases

Early phase reaction consists of
local vasodilation
increased vascular permeability
wheal (local, itchy swelling, or welt)

Immediate inflammatory response in asthma results in bronchial contraction, with
(resulting from mast cell degranulation and subsequent release of histamine and other chemical mediators)

Bronchodilators always reverse bronchospams in
early phase
in more difficult cases of asthma, episode launches a series of steps leading to SLOW inflammatory process that develops 6-8 hours later (LATE PHASE!)

Late-phase can be serious and treatment is aimed at
stopping inflammatory progression before it occurs at this stage

White cells infiltrate the asthmatic airways, as evidence by an
increase in eosinophils and neutrophils

Sloughing of airway cells and growth of goblet cells reults in
hypersecretion of mucus and mucosal swelling
Increased vascular permeability then occurs, causing further MUCUS SECRETION and MUCOSAL SWELLING, which results in MUCUS PLUGGING
(traffic jam of cellular debris and secretions pile up)

Destruction of phospholipid mast cell membrane and its breakdown by phospholipase produces
fatty acid arachidonic acid

Arachodonic acid produces two pathways that contribute to
late phase response

lipoxygenase pathways consist of
leukotriene release

cyclo-oxygenase releases

lipooxygenase, leukotriene, cyclo-oxygenase, prostaglandins add to late phase response of
submucosal edema
mucus production
hyperreactive airways

Drugs that block specific inflammatory pathways, such as
leukotriene inhibitors
prostaglandin inhibitos

Has a broad spectrum of activity and work on several of the different mediator pathways in both early-and late-phase inflammatory responses

can block both initial immune response and subsequent inflammatory process and are a treatment for ALLERGIC ASTHMA

body functions controlled by
nervous system
endocrine system

Endocrine system produces hormones, which are
chemical substances secreted into bloodstream that then circulate and exert physiologic effects on body cells and tissues

Adrenal glands contain
adrenal medulla
adrenal cortex

Adrenal cortex secretes
**related to sympathetic and autonomic nervous system

Adrenal cortex role secretion of
adrenocoritcal hormones/corticosteroids

Corticosteriods classified as

Mineralocorticoids are corticosteroids with salt-retaining activity that are important for
electrolyte balance and fluid volume

Aldosterone produced by
adrenal gland


Aldosterone and Fludocortisone
examples of mineralocorticoids

Aldosterone and Fludocortisone
Increase sodium and water reabsorption by kidney into bloodstream
hich decreases urine production and causes volume expansion within bloodstream

Glucocorticoids affect
fat metabolism

Glucocorticoids useful
pharmacologically for anti-inflammatory activity and their ability to suppress immunologic activity

Synthetic corticosteroids developed to
optimize anti-inflammatory activity (more glucocorticoid-like)
minimize mineralocorticoid activity

Hay fever, also known as allergic rhinitis, is an improper immune response to the introduction of an allergen such as pollen, mold or animal dander into the body. Allergic responses are an interaction between three factors; the allergen, mast cells …

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