Respiratory Agents

Drugs Affecting Upper Respiratory Tract

Antihistamines- drugs that block the release of or action of

histamine, a chemical released during inflammation that
increases secretions and narrows airways
Antitussives- drugs that block the cough reflex
Degongestants- drugs that decrease the blood flow to the upper
respiratory tract and decrease overproduction of secretions
Expectorants- drugs that increase productive cough to clear
airways
Mucolytics- drugs that increase or liquefy respiratory secretions
to aid the clearing of the airways.
How do drugs work?

“drugs always alter normal body function”

You have to know how your body works!

Antihistamine

during allergic reactions:

Antigens circulate in the blood

Histamine and other substances are released from mast cells,

basophils, and other cells in response to antigens circulating in
. the blood.

Histamine molecules then bind to Histamine1 receptor to

activate cells in the nose eyes, ears, respiratory tract, GI
tract and skin producing the characteristic allergic signs and
symptoms

Circulating histamine molecules bind to histamine receptors on

basophils and mast cells. This stimulates further release of histamine
stored within the cells thus producing more allergic reactions.
 How do antihistamines work?
The two types of histamine receptors, H1 and H2, cause different responses.

Antihistamines or H1 blockers/H1 antagonists, work by blocking the histamine

receptors on the surfaces of basophils and mast cells, thereby preventing the
release and actions of histamine stored within the cells.
 They do not push of histamine that is already bound to a receptor but
compete with histamine for unoccupied receptors.
 Therefore, they are most beneficial when given early in a histamine –
mediated reaction, before all free histamine molecules bind to cell
membrane receptors.
 The binding of h1 blockers to these receptors prevents the adverse
consequences of histamine binding: vasodilation, increased GI, respiratory,
salivary and lacrimal secretions and increased capillary permeability with
resultant edema.
 Antigens circulate in the blood

Histamine and other substances are released from mast cells,

basophils, and other cells in response to antigens circulating in
the blood.

Histamine molecules then bind to histamine1 receptor to

activate cells in the nose eyes, ears, respiratory tract, GI
tract and skin producing the characteristic allergic signs and
Antihistamine symptoms

Circulating histamine molecules bind to histamine receptors on

basophils and mast cells. This stimulates further release of histamine
stored within the cells thus producing more allergic reactions.
Classification
1. First Generation- have greater anticholinergic effects
with resultant drowsiness, dizziness, fatigue, blurred
vision, disturbed coordination, urine retention, dry
mouth, nose and throat
Common examples: chlorphenamine, diphenhydramine,
hydroxyzine

2. Second Generation - Usually have less drowsiness,

sedation and lesser anticholinergic symptoms
Common examples: cetirizine, levoceterizine, loratadine
Patient Teaching General

Warn patients to avoid driving a motor vehicle and performing other

dangerous activities if drowsiness occurs or until stabilized on the drug.
• Advise patients to avoid alcohol and other central nervous system
depressants.
• Encourage patients to take drugs as prescribed. Notify a health care
provider if confusion or hypotension occurs.
• Teach patients on prophylaxis for motion sickness to take the drug at
least 30 minutes before the offending event and also before meals and
at bedtime during the event.
• Inform breastfeeding mothers that small amounts of drug pass into
breast milk. Because children are more susceptible to the side effects of
antihistamines (e.g., unusual excitement or irritability), breastfeeding is
not recommended while using these drugs.
Side Effects
• Advise family members or parents that children are more
sensitive to the effects of antihistamines. Nightmares,
nervousness, and irritability are more likely to occur in
children.
• Inform older adults that they are more sensitive to the
effects of antihistamines and are more likely to experience
confusion, difficult or painful urination, dizziness, drowsiness,
feeling faint, and dryness of the mouth, nose, or throat.
• Suggest using sugarless candy or gum, ice chips, or a saliva
substitute for temporary relief of mouth dryness.
 Antitussives

• The cough is a naturally protective way to

clear the airway of secretions or any collected
material. If the cough is nonproductive and
irritating, an antitussive may be taken
Presence of respiratory disorders such as common cold, sinusitis,
pharyngitis and pneumonia (diseases that are accompanied by
uncomfortable, unproductive cough )

Receptors in the bronchi, alveoli and pleura(lining of the lungs )

are stretched

Signal is sent to the cough center of the brain, medulla,

stimulating cough reflex
 So how do Antitussives work?

Antitussives work by acting on the cough-

control center in the medulla to suppress the
cough reflex
 Presence of respiratory disorders such as common cold, sinusitis,
pharyngitis and pneumonia (diseases that are accompanied by
uncomfortable, unroductive cough )

Receptors in the bronchi, alveoli and pleura(lining of the lungs ) are

stretched

Signal is sent to the

cough center of the brain, medulla, stimulating cough reflex

Antitussives
Types

Opioid
Nonopioid
 Combination preparations
Opioid
Works by suppressing the cough reflex through direct
action at the cough center in the CNS (medulla )
• All opoid drug has antitussive effect but only codeine
and hydrocone are used as antitussives. Also causes
analgesia, drying effect in the mucosa which increases
viscosity in the oral mucosa.
• If taken in prescribed manner, will not lead to
dependency
• Opoid drugs are commonly incorporated to various
combinations
Nonopioid

Works in the same way as opoid but does not

cause analgesia or CNS depression.
Example: dextromethorphan
Adverse Effects
Because they affect the centers in the brain,
antitussives are associated with CNS adverse
effects, including drowsiness, sedation,
respiratory depression.
Traditonal antitussives have drying effect on
the mucuos membranes and can increase the
viscosity of respiratory tract secretions. This
may lead to nausea, constipation, and
complaints of dry mouth.
Expectorants
Drugs that aid expectoration ( coughing
up/spitting out). It increase productive cough to
clear airways

Productive cough caused by cold, bronchitis,

laryngts, influenza, etc.

Production and accumulation of excessive

mucus secretions in the lungs
Expectorants
 How do expectorants work?
Depending on the drug either ...

a) a. Reflex stimulation in which loosening and

thinning of respiratory tract secretions occur
in response to irritation of GI Tract produced
by the drug
b) Direct stimulation of secretory glands in the
respiratory tract.
• The most common expectorant is guaifenesin.
It works by enhancing output of the
respiratory tract fluids by reducing the
adhesiveness and surface tension of these
fluids allowing easier movement of less
viscous secretions.
Adverse Effects

• Most common adverse effects associated with

expectorants are GI symptoms: nausea,
vomitting, anorexia. Some experience,
dizziness, headache or both.
Considerations
• Hydration is the best natural expectorant. When
taking an expectorant, patients should increase fluid
intake to at least 8 glasses per day to help loosen
mucus.
• May mask important symptoms of underlying
disorder therefore it should not be taken for more
than 1 week. If cough persists, encourage pt to seek
healthcare.
Mucolytics- works by increasing or liquefying respiratory secretions
to break down mucus and aid the clearing of the airways.
Example: Acetylcysteine

Patients suffering from conditions such as COPD,

cystic fibrosis, pneumonia and tuberculosis.

Production of thick, tenacious mucus secretions in

the lungs

Mucolytics
Degongestants- drugs that decrease the blood flow to the upper
respiratory tract and decrease overproduction of secretions

Dilation of nasal blood vessels caused by

infection, inflammation or allergy

Transudation of fluid into tissue spaces, resulting

into swelling of nasal cavity

Excessive nasal secretion and inflamed, swollen

nasal mucosa

Nasal congestion
Classificatons
1. Adrenergics ( sympathomemetics)- works by stimulating the alpha
adrenergic receptors producing vascular constriction
(vasoconstriction) of capillaries within nasal mucosa. Once swollen
blood vessels shrink, nasal secretions are better able to drain either
externally (nostril) or internally through absorption into blood stream.
2. Topical corticosteroids (Intranasal steroids- ) aimed at the
inflammatory response elicited by invading organisms ( viruses and
bacteria) or other antigens (e.g. allergens ). The body responds to
these antigens by producing inflammaton in an effort to isolate or wall
off the area and by attracting various cells of the immune system to
consume and destroy the offending antigens. Steroids exert their
antiinflammatory effect by causing these cells to be turned off or
rendered unresponsive.
Considerations
• Decongestants can be taken orally to produce a systemic effect, inhaled or
can be administered topically to the nose.
• Drugs administered via oral route produce prolonged decongestant
effects, but the onset of action is more delayed and the effect less potent
that for decongestants applied topically.
• Clinical problem of rebound congestion may occur with repeated use of
inhaled corticosteroids because of the very rapid absorption of drugs
through mucus membranes followed by the rapid decline in therapeutic
activity.
• This rebound congestion may lead to overuse and dependence on the
nasal spray, as patients take it frequently due to the rapid decline in
activity.
• Commonly used intranasal steroids include the
following:
Budesonide (rhinocort)
Flunisolide (nasalide)
Fluticasone (flonase)
• The only intranasal anticholinergic drug in use is
ipratropium nasal spray (atrovent)
Side effects/adverse reactions
– Excessive dosages of these medications are likely to
cause systemic effects elsewhere in the body. These
may include cardiovascular effects such as headache,
dizziness, nervousness. These sytemic effects are the
result of alpha-adrenergic stimulaton of the heart,
blood vessels, CNS.
– Rebound nasal congestion if use is prolonged
Chronic Obstructive Pulmonary
Disease (COPD)
• Pathophysiologic changes
 Airway obstruction with increased airway resistance
of airflow to lung tissues
• Major causes
 Chronic bronchitis
 Bronchiectasis
 Emphysema
 Asthma

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Chronic Obstructive Pulmonary
Disease (COPD) (Cont.)

Signs and Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Conditions

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 Restrictive Lung Disease
• Pathophysiologic changes
 Decrease in total lung capacity due to fluid
accumulation and loss of elasticity of lung
tissues
• Etiology
 Pulmonary edema
 Pulmonary fibrosis
 Pneumonitis
 Lung tumors
 Thoracic deformities (scoliosis)
 Myasthenia gravis

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 Asthma
• Inflammatory disorder of the airway walls
associated airway obstruction
• Triggers
– Stress
– Allergens
– Pollutants
• Signs/symptoms
 Bronchospasm, dyspnea, mucus secretions
 Wheezing, coughing, tightness in the chest

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 Bronchial Asthma
• Pathophysiologic changes
– Allergens attach to mast cells and basophils
causing antigen-antibody reaction on mast cells.
– Mast cells stimulate release of chemical mediators.
– Inflammatory process occurs.
– Resistance to airflow from airway obstruction.
• Signs/symptoms
– Bronchospasm, wheezing
– Dyspnea, mucus secretions

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Bronchial Asthma (Cont.)

Factors Contributing to Bronchoconstriction

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Fig. 36.2 shows factors that contribute to
bronchoconstriction. Cyclic adenosine
monophosphate (cyclic AMP, or cAMP), a cellular
signaling molecule, is involved in many cellular
activities and is responsible for maintaining
bronchodilation. When histamine, ECF-A, and
leukotrienes inhibit the action of cAMP,
bronchoconstriction results.
 Chronic Bronchitis
• Pathophysiologic changes
– Bronchial inflammation and excessive mucus
secretions lead to airway obstruction.
• Causes
– Smoking
– Chronic lung infections
• Signs/symptoms
– Excessive mucous secretion, productive cough
– Rhonchi, hypercapnia, respiratory acidosis
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 Bronchiectasis
• Pathophysiologic changes
– Abnormal dilation of bronchi and bronchioles
– Bronchioles become obstructed by the
breakdown of epithelium of bronchial mucosa.
– Tissue fibrosis may result.
• Causes
– Frequent infection
– Inflammation

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 Emphysema
• Pathophysiologic changes
– Proteolytic enzymes released in the lung by
bacteria or phagocytic cells.
– Terminal bronchioles become plugged with
mucus leading to a loss in fiber and elastin
network in alveoli.
– Alveolar walls are destroyed.
– Air trapped in enlarged, overexpanded alveoli.
– Resulting in an inadequate gas exchange.

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 Emphysema (Cont.)
• Causes
– Cigarette smoking
– Atmospheric contaminants
– Lack of the alpha1-antitrypsin protein

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Treatment Of Diseases In The Lower
Respiratory Tract
• The tracheobronchial tube is
composed of smooth muscle
whose fibers spiral around the
tracheobronchial tube, becoming
more closely spaced as they near
the terminal bronchioles

• Beta2 adrenergic receptors are

located throughout the lungs

• When the beta2 receptors in the

bronchial smooth muscle are
stimulated , it results in
bronchodilation.
• The tracheobronchial tube is
composed of smooth muscle
whose fibers spiral around the
tracheobronchial tube, becoming
more closely spaced as they near
the terminal bronchioles

• Cyclic adenosine monophosphate

(cyclic AMP, or cAMP) in the
cytoplasm of brochial cells, a
cellular signaling molecule, is
involved in many cellular
activities and is responsible for
maintaining bronchodilation by
relaxing the bronchial smooth
muscles.
• When histamine, ECF-A, and
leukotrienes inhibit the action of
cAMP, bronchoconstriction
results.
• The pulmonary enzyme
phosphodiesterase can inactivate
cAMP.
Bronchodilators: Beta Adrenergic Agonists

(Mechanism of action: When beta2 adrenergic receptors is

stimulated by B2 agonists, level of cAMP is increased resulting to
bronchial dilation and increased airflow to the lungs.

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There are 3 subtypes of these drugs based on
selectivity for B2 receptors:
1. Non selective adrenergic drugs which stimulate beta1 (cardiac ) and beta2 (
respiratory) receptors.
Example: Epinephrine
– Side effects
• Dizziness, nervousness, tremors, hypertension
• Palpitations, tachycardia, dysrhythmias, angina

2. Non selective beta adrenergic drugs which stimulate beta1 and beta2
receptors.
Example: metaproterenol
• Common side effects
– Headache, tremor, nausea, Palpitations, tachycardia
3. Selective beta2 drugs whch primarily stimulate beta2 receptors.
Example: albuterol
• Common side effects
– Headache, rhinitis, excitability, tremors, Bronchospasm, palpitations,
tachycardia
Bronchodilators: Anticholinergics

Currently, there are four anticholinergc drugs used in

the treatment of COPD: Ipratropium (Atrovent),
Triotropium ( Spiriva), Aclidinum ( Tudorza), Vilanterol
( Anoro Ellipta)

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• The tracheobronchial tube is composed
of smooth muscle whose fibers spiral
around the tracheobronchial tube,
becoming more closely spaced as they
near the terminal bronchioles
• Contraction of these muscles constricts
the airway.
• The sympathetic and parasympathetic
nervous systems affect the bronchial
smooth muscle in opposite ways.
• On the surface of the bronchial tree
are receptors of acetylcholne ( ACh).
• When the vagus nerve
(parasympathetic nervous system)
releases acetylcholine it binds to the
ACh receptors on the bronchial tree
which causes bronchial constriction and
narrowing of the airways
 Anticholinergic Mechanism of action:

When the PSNS releases ACh from its nerve endings,

anticholnergic drugs bind to the ACh receptors on the
surface of the bronchial tree, which results n bronchial
constriction and narrowing of the airways.
Anticholineric drugs block the Ach receptors to prevent
bronchoconstrction.
Bronchodilators: Xanthine Derivatives

• Methylxanthine (xanthine) derivatives, include

aminophylline, theophylline, and caffeine.
• Because of their effect on respiration and pulmonary
vessels, xanthines are used in the treatment of asthma.

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• The tracheobronchial tube is
composed of smooth muscle
whose fibers spiral around the
tracheobronchial tube, becoming
more closely spaced as they near
the terminal bronchioles

• Cyclic adenosine monophosphate

(cyclic AMP, or cAMP) in the
cytoplasm of brochial cells, a
cellular signaling molecule, is
involved in many cellular
activities and is responsible for
maintaining bronchodilation by
relaxing the bronchial smooth
muscles.
• When histamine, ECF-A, and
leukotrienes inhibit the action of
cAMP, bronchoconstriction
results.
• The pulmonary enzyme
phosphodiesterase can inactivate
cAMP.
Mechanism of action:

 Xanthine derivatives competetively inhibt

phosphodiesterase, the enzyme responsible
for breaking down cAMP.
 Higher intracellular levels of cAMP contribute
to smooth muscle relaxation and also inhibit
IgE induced release of chemical mediators that
drive allergic reactions
Mechanism of action:

 Theophylline is metabolized to caffeine and

aminophylline is metabolized to theophylline.
 Theophylline and other xanthines stimulate the CNS,
but to a lesser degree than caffeine.
 This stimulation of the CNS has the beneficial effect
of acting directly on the medullary respratory center
to enhance medullary drive.
• In large doses, theophylline may stimulate the
cardiovascular system, which results in both
increased or of contracton ( positive inotropy) and
ncreased heart rate (positive chronotropy). The
increased force of contraction raises cardiac output
and hence, increased blood flow in the kdneys. This,
in combination of the xanthines ability to dilate
blood vessels in and around the kidney increases
glomerular filtration rate , which produces diuretic
effect.
• Side effects/adverse effects
– Dizziness, headache, irritability
– Nervousness, irritability, hyperreflexia
– GI distress, intestinal bleeding
– Seizure, insomnia, hyperglycemia
– Tachycardia, palpitations
– Hypotension, dysrhythmias

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General Nursing Interventions for Bronchodilators

 Monitor vital signs.

 Provide adequate hydration.
 Observe for side effects.
 Administer medication at regular intervals around the
clock to have a sustained therapeutic level.
 Advise patient having asthmatic attacks to wear an
identification bracelet or MedicAlert tag.

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Non-bronchodilating Respiratory Drugs

Other than bronchodilators, there are also other

drugs that are effective in supressing the various
underlying causes of respiratory drugs.
1. Leukotriene Receptor Antagonists

• Leukotriene (LT) is a chemical mediator that

can cause inflammatory changes in the lung.
The cysteinyl leukotrienes promote an
increase in eosinophil migration, mucus
production, and airway wall edema, which
result in bronchoconstriction.

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Factors Contributing to Bronchoconstriction

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Mechanism of Action

• Leukotriene receptor antagonists selectively and

copetetively block ( e.g zafirlukast, montelukast)
or antagonize (e.g zileuton) receptors for the
production of leukotrines D4 and E4 as a result,
these drugs block many of the signs and symptoms of
asthma.
2. Glucocorticoids (Steroids)
Glucocorticoids, members of the corticosteroid family,
are used to treat respiratory disorders, particularly
asthma. These drugs have an antiinflammatory action
and are indicated if asthma is unresponsive to
bronchodilator therapy or if the patient has an
asthmatic attack while on maximum doses of
theophylline or an adrenergic drug.
Mechanism of Action

• Corticosteroids produce antiinflammatory effects

through a complex sequence of actions.
Corticosteroids essentially work by stabilizing the
membranes of cells that normally release
bronchoconstricting substances. These cells include
five types of WBCs who has a role in the
inflammatory process.
Mechanism of Action
Corticosteroids have also been shown to restore
or increase the responsiveness of bronchial
smooth muscle to beta adrenergic receptor
stimulation, which results in more pronounced
stimulaton of beta2 receptors by beta agonist
drugs such as albuterol.
• Administration
– MDI inhaler, tablet, intravenous
• Side/Adverse effects
– Immunosuppresson
– Dry mouth, throat irritation, hoarseness
– Headache, euphoria, confusion, depression
– Hyperglycemia, GI distress, hypertension
– Electrolyte imbalance, fluid retention
– Osteoporosis, psychosis, superinfections
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 Cromolyn
• Action
Cromolyn sodium is used for prophylactic treatment of bronchial
asthma, and it must be taken daily. It is not used for acute
asthmatic attacks. Cromolyn does not have bronchodilator
properties but instead acts by inhibting release of histamine and
other inflammatory mediators from mast cells to prevent an
asthma attack.
• Common side effects
– Cough, bad taste
• Adverse effect
-- The drug should not be discontinued abruptly because a
rebound asthmatic attack can result.
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