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Part 5: Drugs Affecting
the Respiratory System.
Drugs affecting the URT:
Antihistamines:
Older:
I. Anti-histamines
Histamine is a bodily substance that performs many
functions. It is involved in nerve impulse transmission in
the central nervous system CNS, dilation of capillaries,
contraction of smooth muscles, stimulation of gastric
secretion, and acceleration of the heart rate.
There are two types of cellular receptors for histamine.
Histamine 1 H1 receptors mediate smooth muscle
contraction and dilation of capillaries, and histamine 2 H2
receptors mediate acceleration of heart rate and gastric
acid secretion. This explains why the release of excessive
amounts of histamine can lead to anaphylaxis and severe
allergic symptoms and may result in any or all of the
following physiologic changes:
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Chlorpheniramine.
Clemastine.
Diphenhydramine.
Promethazine.
Hydroxyzine.
Nonsedating or Second generation:
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Loratadine.
Cetrizine.
Desloratidine.
Levocetrizine.
Fexofenadine.
Constriction of smooth muscle, especially in the stomach and lungs.
Increase in body secretions.
Vasodilation and increased capillary permeability, which results in the movement of fluid out
of the blood vessels and into the tissues and thus causes a drop in blood pressure and
edema.
Antihistamines are drugs that directly compete with histamine for specific receptor sites. They also
called histamine antagonists. Antihistamines that compete for the H2 receptors are called H2
antagonists and include such drugs as ranitidine and famotidine, they are discussed in detail in
GIT. This chapter focuses on the H1 antagonists; these are the drugs more commonly known by
the name antihistamines.
The clinical efficacy of the different antihistamines is very similar, although they have varying
degrees of antihistaminic, anticholenergic, and sedating properties. The particular actions of
particular antihistamines are determined by its specific chemical makeup. These drugs also differ
from each other in their potency and their adverse effects, especially in the degree of drowsiness
they produce.
Mechanism of action:
 The binding of H1 blockers to the histamine receptors prevents the adverse consequences of
histamine stimulation
 More effective in preventing the actions of histamine rather than reversing them
 Should be given early in treatment, before all the histamine binds to the receptors
Antihistamine effects:
Cardiovascular (small blood vessels)
 Histamine effects: Dilation and increased permeability (allowing substances to leak into
tissues)
 Antihistamine effects: Reduce dilation of blood vessels and Reduce increased permeability
of blood vessels
Smooth muscle (on exocrine glands)
 Histamine effects : Stimulate salivary, gastric, lacrimal, and bronchial secretions
 Antihistamine effects: Reduce salivary, gastric, lacrimal, and bronchial secretions
Immune system (release of substances commonly associated with allergic reactions)
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Histamine effects: Mast cells release histamine and other substances, resulting in allergic
reactions
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Antihistamine effects: Binds to histamine receptors, thus preventing histamine from
causing a response
Skin : Reduce capillary permeability, wheal-and-flare formation, itching
Anticholinergic : Drying effect that reduces nasal, salivary, and lacrimal gland secretions (runny
nose, tearing, and itching eyes)
Sedative : Some antihistamines cause drowsiness
Indications:
 Management of:
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Nasal allergies
Seasonal or perennial allergic rhinitis (hay fever)
Allergic reactions
Motion sickness
Sleep disorders
 Also used to relieve symptoms associated with the common cold
 Sneezing, runny nose
 Palliative treatment, not curative
Side effects:
 Anticholinergic (drying) effects, most common: Dry mouth, Difficulty urinating, Constipation,
and Changes in vision
 Drowsiness: Mild drowsiness to deep sleep
Types of antihistamines:
1- Traditional antihistamines or First generation:
 Older and Work both peripherally and centrally.
 Have anticholinergic effects, making them more effective than nonsedating drugs in some
cases
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Chlorpheniramine.
Clemastine.
Diphenhydramine.
Promethazine.
Hydroxyzine.
2- Nonsedating or Second generation:
 Developed to eliminate unwanted adverse effects, mainly sedation
 Work peripherally to block the actions of histamine; thus, fewer CNS adverse effects
 Longer duration of action (increases compliance)
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Loratadine.
Cetrizine.
Desloratidine.
Levocetrizine.
Fexofenadine.
Nursing implications:
 Gather data about the condition or allergic reaction that required treatment; also assess for
drug allergies
 Contraindicated in the presence of acute asthma attacks and lower respiratory diseases,
such as pneumonia
 Use with caution in increased intraocular pressure, cardiac or renal disease, hypertension,
asthma, COPD, peptic ulcer disease, BPH, or pregnancy
 Instruct patients to report excessive sedation, confusion, or hypotension
 Instruct patients to avoid driving or operating heavy machinery; advise against consuming
alcohol or other CNS depressants
 Instruct patients not to take these medications with other prescribed or over-the-counter
medications without checking with prescriber
 Best tolerated when taken with meals—reduces GI upset
 If dry mouth occurs, teach patient to perform frequent mouth care, chew gum, or suck on
hard candy (preferably sugarless) to ease discomfort
 Monitor for intended therapeutic effects
II: Bronchodilators and Other Respiratory
Drugs.
Diseases of the lower respiratory system:
 Asthma.
 Emphysema.
 Chronic bronchitis
Chronic obstructive pulmonary disease COPD is the name applied collectively to emphysema and
chronic bronchitis. Asthma that is persistent and present most of the time despite treatment is also
considered a COPD.
Asthma:
Bronchial asthma is defined as a recurrent and reversible shortness of breath and occurs when the
airways of the lung become narrow as a result of bronchospasm, inflammation and edema of the
bronchial mucosa, and the production of viscous mucus. Wheezing and difficulty breathing are
symptoms. When an episode has a sudden and dramatic onset, it is referred to as an asthma
attack.
Most asthma attacks are short, and normal breathing is subsequently recovered. However, an
asthma attack may be prolonged for several minutes to hours and may not respond to typical drug
therapy. This is a condition known as status asthmaticus and often requires hospitalization.
Asthma is an inflammatory disease of the airways characterized by episodes of acute
bronchoconstriction causing shortness of breath, Cough, Wheezing, and Chest tightness.
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The cause of the disease is unknown.
Asthma is a chronic inflammatory disease.
 The attacks are precipitated by trigger factors such as Infections, Exercise, Food, Strong
odors, Smoking, Allergens, and Medications like aspirin and NSAIDs
Chronic bronchitis:
Chronic bronchitis is a continuous inflammation of the bronchi. The inflammation in the associated
bronchioles is responsible for most airflow obstruction. Chronic bronchitis involves the excessive
secretion of mucus and certain pathologic changes in the bronchial structure. The disease can arise
as a result of repeated episodes of acute bronchitis or in the context of chronic generalized diseases.
It is usually precipitated by prolonged exposure to bronchial irritants. One of the most common is
cigarette smoke.
Emphysema:
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Air spaces enlarge as a result of the destruction of alveolar walls
The surface area where gas exchange takes place is reduced
Effective respiration is impaired
Cigarette smoke appears to be the primary irritant responsible for precipitating the
underlying inflammation that leads to the development of emphysema.
Treatment of diseases of the lower respiratory tract system:
Pharmacology overview:
A. Bronchodilators:
They are able to relax bronchial smooth bans to dilate the bronchi and bronchioles that are narrowed
as a result of the disease process. There are three classes of such drugs: beta agonists,
anticholinergics, and xanthine derivatives.
1- Beta-Adrenergics Agonists:
Mechanism of action:
The beta agonists dilate airways by stimulating the beta2 adrenergic receptors located throughout
the lungs. There are two types of these drugs:
1- Nonselective adrenergics drugs, which stimulating the beta1 and beta2 receptors,
example: Epinephrine (given by subcutaneous).
2- Selective beta2 drugs, which primarily stimulate the beta2 receptors, example:
salbutamol, terbutalin, salmetrol, and formetrol.
Activation of beta2 receptors activates adenylate cyclase, which is an enzyme needed to make cyclic
adenosine monophosphate (cAMP), this results in produce more cAMP which relaxes smooth
muscle in the airway and results in bronchial dilation and increased airflow
 Short acting: Salbutamol: Oral or by inhalation. Terbutalin: Oral.
 Long acting: Formetrol and salmetrol: inhalation.
Indications:
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Relief of bronchospasm related to asthma, bronchitis, and other pulmonary diseases
Used in treatment and prevention of acute attacks (inhaled salbutamol).
Used in hypotension and shock (epinephrine)
Used to produce uterine relaxation to prevent premature labor (oral salbutamol and oral
terbutalin)
Adverse effects:
 Alpha and beta (epinephrine): Insomnia, Restlessness, Anorexia, Vascular headache,
Hyperglycemia, Tremor, Cardiac stimulation
 Beta 2 agonists: Hypotension OR hypertension, Vascular headache, Tremor, and
tachycardia.
Drug profile:
Salbutamol:
 At large doses lose their selectivity, this lead to adverse effects like nausea and palpitation.
 Used in acute attack by inhalation because the rapid onset of action (immediate), half-life up
to 3-4 hours.
Salmetrol:
 Used for maintenance treatment of asthma and COPD.
 Given twice daily (half-life 12 hours).
2- Anticholenergics:
Ipratropium and tiotropium.
Mechanism of action:
 Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways
 Anticholinergics bind to the ACh receptors, preventing ACh from binding
 Result: bronchoconstriction is prevented, airways dilate
Indications:
Because their actions are slow and prolonged, anticholinergics are used for prevention of the
bronchospasm associated with chronic bronchitis or emphysema and not for the management of
acute symptoms.
Adverse effects:
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Dry mouth or throat
Heart palpitations
Gastrointestinal distress
Headache
Coughing
Anxiety
Drug profile:
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These drugs can’t be taken by mouth, but taken by inhalation.
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Ipratropium (Atrovent):
 Onset of action: 15 min
 Duration: 4 hours.
 Dosage form: aerosol, solution for inhalation.
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Tiotropium (Spiriva):
 Long acting up to 20 hours.
 Given once daily.
 Dosage form: powder for inhalation.
3- Xanthine derivatives (Aminophylline (given parentrally) and theophylline
(given orally).)
Mechanism of action:
 Increase levels of energy-producing cAMP, this is done competitively inhibiting
phosphodiesterase (PDE), the enzyme that breaks down cAMP.
 Result: decreased cAMP levels, smooth muscle relaxation, bronchodilation, and
increased airflow
 Also cause cardiovascular stimulation: increased force of contraction and increased
heart rate, resulting in increased cardiac output and increased blood flow to the kidneys
(diuretic effect)
 Also cause CNS stimulation.
Indications:
Xanthines may be used in mild to moderate cases of acute asthma and as an adjunct drug in the
management of COPD. However, xanthines are now deemphasized as treatment for milder asthma
because of their greater potential for drug interactions and narrow therapeutic index. They are often
used for the prevention of asthmatic symptoms than for relief of acute asthma attacks.
Adverse effects:
 Nausea, vomiting, anorexia
 Tachycardia.
B. Nonbronchodilating respiratory drugs:
1- Leukotriene respiratory antagonists (LRAs):
 Montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo). Montelukast is the
only one found in the market.
Mechanism of action:
 Leukotrienes are substances released when a trigger, such as cat hair or dust, starts a
series of chemical reactions in the body. Leukotrienes cause inflammation,
bronchoconstriction, and mucus production this result in coughing, wheezing, and
shortness of breath
 LRAs As prevent leukotrienes from attaching to receptors on cells in the lungs and in
circulation Inflammation in the lungs is blocked, and asthma symptoms are relieved
 By blocking leukotrienes:
 Prevent smooth muscle contraction of the bronchial airways
 Decrease mucus secretion
 Prevent vascular permeability
 Decrease neutrophil and leukocyte infiltration to the lungs, preventing
inflammation
Indications of montelukast:
 Prophylaxis and chronic treatment of asthma in adults and children ages 2 and older, and for
treatment of allergic rhinitis. NOT meant for management of acute asthmatic attacks
Adverse effects:
 Zileuton: Headache, dyspepsia, nausea, dizziness, insomnia, liver dysfunction
 Zafirlukast: Headache, nausea, diarrhea, liver dysfunction
 Montelukast has fewer adverse effects
2- Corticosteroids:
They also had known as glucocorticoids and used in the treatment of pulmonary diseases for their
anti-inflammatory effects. They can be given by inhalation, orally, or even intravenously in severe
cases of asthma. Inhalation prevents systemic adverse effects of corticosteiods. Corticosteroids may
take several weeks before full effect can be seen.
Corticosteroids given by inhalation:
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Beclomathasone.
Budesonise.
Flunisolide.
Fluticasone.
Systemic effects:
 Dexamethasone: oral or parenteral.
 Prednisone: oral.
 Methylprednisonlone I.V or oral.
Mechanism of action:
The exact mechanism of action of the corticosteroids has not been determined. They have the dual
effect of both reducing inflammation and enhancing the activity of beta agonists. They work by
stabilizing the membranes of leukocyte cells that normally release very harmful bronchoconstricting
substances. They also have been shown to increase the responsiveness of bronchial smooth muscle
to beta-adrenergic receptor stimulation, which results in more pronounced stimulation of the beta2
receptors by beta agonist drugs.
Indications:
They are used concurrently with bronchodilators, primarily beta-adrenergic agonists. Systemic
corticosteroids are generally used only to treat acute exacerbations, or severe asthma.
Adverse effects:
 Pharyngeal irritation, Coughing, Oral fungal infections.
 Systemic effects are rare because low doses are used for inhalation therapy
Inhalers:
First-line drugs for treatment of asthma:
 Beta-Agonists, and corticosteroids.
Alternative drugs to treat asthma:
 Leukotriene antagonists, anticholinergics, xanthine derivaties, omalizumab (monoclonal
antibody antiasthmatic, given by injection)
Drugs used to treat COPD:
 Anticholinergics and beta-Agonists (can be used as combination)
Nursing implications:
 Encourage patients to take measures that promote a generally good state of health so as to
prevent, relieve, or decrease symptoms of COPD
 Avoid exposure to conditions that precipitate bronchospasm (allergens, smoking, stress, air
pollutants)
 Adequate fluid intake
 Compliance with medical treatment
 Avoid excessive fatigue, heat, extremes in temperature, caffeine
 Encourage patients to get prompt treatment for flu or other illnesses, and to get vaccinated
against pneumonia or flu
 Perform a thorough assessment before beginning therapy, including:
Skin color, Baseline vital signs, Respirations (should be between 12 and 24 breaths/min), Sputum
production, Allergies, History of respiratory problems, Other medications
 Teach patients to take bronchodilators exactly as prescribed
 Ensure that patients know how to use inhalers and MDIs, and have patients demonstrate use
of the devices
 Monitor for adverse effects
 Monitor for therapeutic effects
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Decreased dyspnea
Decreased wheezing, restlessness, and anxiety
Improved respiratory patterns with return to normal rate and quality
Improved activity tolerance
Decreased symptoms and increased ease of breathing
Beta-agonist derivatives
 salbutamol, if used too frequently, loses its beta2-specific actions at larger doses
 As a result, beta1 receptors are stimulated, causing nausea, increased anxiety,
palpitations, tremors, and increased heart rate
 Ensure that patients take medications exactly as prescribed, with no omissions or
double doses
 Inform patients to report insomnia, restlessness, palpitations, chest pain, or
any change in symptoms
Xanthine derivatives:
 Contraindications: history of PUD or GI disorders
 Cautious use: cardiac disease
 Timed-release preparations should not be crushed or chewed (cause gastric irritation)
 Report to physician: Palpitations, Weakness, Convulsions, Nausea, Dizziness,
Vomiting, and Chest pain
 Be aware of drug interactions with cimetidine, oral contraceptives, allopurinol, certain
antibiotics, others
Leukotrien receptor antagonists LRAs:
 Ensure that the drug is being used for chronic management of asthma, not acute asthma
 Improvement should be seen in about 1 week
 Advise patients to check with physician before taking over-the-counter or prescribed
medications—there are many drug interactions
 Assess liver function before beginning therapy
 Teach patient to take medications every night on a continuous schedule, even if symptoms
improve
Inhaled corticosteroids:
 Contraindicated in patients with psychosis, fungal infections, AIDS, TB
 Teach patients to gargle and rinse the mouth with lukewarm water afterward to prevent the
development of oral fungal infections
 If a beta-agonist bronchodilator and corticosteroid inhaler are both ordered, the
bronchodilator should be used several minutes before the corticosteroid to provide
bronchodilation before administration of the corticosteroid
 Encourage use of a spacer device to ensure successful inhalations
 Teach patient how to keep inhalers and nebulizer equipment clean after uses
Inhalers: Patient Education
 For any inhaler prescribed, ensure that the patient is able to self-administer the medication
 Provide demonstration and return demonstration
 Ensure that the patient knows the correct time intervals for inhalers
 Provide a spacer if the patient has difficulty coordinating breathing with inhaler
activation
 Ensure that the patient knows how to keep track of the number of doses in the inhaler
device