2. Respiratory Drugs
The respiratory agents presented here are divided into two primary categories.
The first group includes drugs that treat acute and relatively minor problems, such as
and seasonal allergies.
The second category includes drugs that treat more chronic and serious airway obstructions,
Antitussive drugs are used to suppress coughing associated with the common cold and other
minor throat irritations.
Antitussives are usually recommended for short-term use in relieving symptomatic coughing
Coughing is a type of defense mechanism that can help expel mucus and foreign material from
the upper respiratory tract
Antitussives may be helpful in treating an annoying dry cough, but use of these drugs to treat an
active and productive cough may not be justified
codeine and similar opiate derivatives suppress the cough reflex by a central inhibitory effect
Other nonopioid antitussives work by inhibiting the irritant effects of histamine on the respiratory
mucosa or by a local anesthetic action on the respiratory epithelium.
Congestion within and mucous discharge from the upper respiratory tract are familiar symptoms
of many conditions.
Allergies, the common cold, and various respiratory infections often produce a runny nose and a
stuffy head sensation
Decongestants used to treat these symptoms are usually alpha-1–adrenergic agonists
MOA: These agents bind to alpha-1 receptors located on the blood vessels of the nasal mucosa
and stimulate vasoconstriction, thus effectively drying up the mucosal vasculature and
decreasing local congestion in the nasal passages
Depending on the preparation, these agents may be taken systemically or applied locally to the
nasal mucosa via aerosol sprays
The primary adverse effects associated with decongestants are headache, dizziness,
nervousness, nausea, and cardiovascular irregularities (increased blood pressure, palpitations).
Histamine is an endogenous chemical that is involved in the normal regulation of certain
physiologic functions (gastric secretion, CNS neural modulation), as well as various
hypersensitivity (allergic reactions).
Histamine exerts its effects on various cells through four primary receptor subtypes:
and H4 receptors
Antihistamines are drugs that specifically block the H1 subtype of histamine receptors; that is, the
effects of histamine during allergic reactions, respiratory infections, and so forth are mediated
primarily through the H1 receptor located on vascular, respiratory, and other tissues.
H2 receptors are involved primarily in the regulation of gastric acid secretion. Drugs that
selectively block the H2 receptor (referred to simply as H2 antagonists) may help control gastric
secretion in conditions such as peptic ulcer;
A third receptor subtype, the H3 receptor, has been identified, and this subtype may be involved in
the local regulation of histamine release from CNS nerve terminals
► a new H4 receptor has been identified on blood cells or cells derived from blood cells.
► The clinical and pharmacologic significance of H3 and H4 receptors remains to be determined.
Therapeutic indications of Antihistamines
By blocking the effects of histamine on the upper respiratory tissues, these drugs help
Nasal congestion, mucosal irritation and discharge (rhinitis, sinusitis), and conjunctivitis that are
caused by inhaled allergens.
Similarly, antihistamines may decrease the coughing and sneezing associated with the common
Antihistamines may be used as an adjunct in patients with asthma to help control rhinitis and
The primary adverse effects associated with antihistamines are sedation, fatigue, dizziness,
blurred vision, and incoordination.
Gastrointestinal distress (nausea, vomiting) is also quite common. Certain side effects, however,
are related directly to each drug’s ability to cross the blood-brain barrier
The original or “first-generation” antihistamines readily cross the blood-brain barrier and enter
the brain, thus causing CNS-related side effects such as sedation and psychomotor slowing
Do not easily cross the blood brain barrier, and the risk of sedation and other CNS side
effects is reduced
15. Mucolytics and Expectorants
Mucolytic drugs attempt to decrease the viscosity of respiratory secretions
Expectorant drugs facilitate the production and ejection of mucus.
These drugs are used to prevent the accumulation of thick, viscous secretions that can clog
respiratory passages and lead to pulmonary problems.
The primary mucolytic drug currently in use is acetylcysteine.
This drug is thought to work by splitting the disulfide bonds of respiratory mucoproteins, thus
forming a less viscous secretion.
Acetylcysteine is usually administered directly to the respiratory mucosa by inhalation or
intratracheal instillation (through a tracheostomy)
The primary adverse effects associated with this drug include nausea, vomiting, inflammation
of the oral mucosa (stomatitis), and rhinorrhea. However, serious adverse effects are relatively
Several expectorant agents have been used in the past, but guaifenesin is the only drug
currently acknowledged by the FDA to have evidence of therapeutic effects
This drug is administered to increase the production of respiratory secretions, thus
encouraging ejection of phlegm and sputum
The primary adverse effect associated with guaifenesin is gastrointestinal upset, which is
exacerbated if excessive doses are taken or if this drug is taken on an empty stomach.
18. Chronic Obstructive
Chronic obstructive pulmonary disease, or COPD,
refers to a group of diseases that cause airflow
blockage and breathing-related problems
Chronic bronchitis irritates your bronchial tubes,
which carry air to and from your lungs. In response,
the tubes swell and mucus (phlegm) builds
up along the lining. The buildup narrows the tube’s
opening, making it hard to get air into and out of your
19. Chronic Obstructive
Emphysema is the breakdown of the walls of the tiny air sacs (alveoli) at the end of the bronchial
tubes, in the “bottom” of your lung.
Drugs used are;
Bronchodilators (beta-adrenergic agonists)
and anti-inflammatory agents (glucocorticoids,others)
20. Beta-Adrenergic Agonists
Respiratory smooth-muscle cells contain the beta-2 subtype of adrenergic receptors.
Stimulation of these beta-2 receptors results in relaxation of bronchiole smooth muscle.
Hence, drugs that stimulate these beta-2 adrenergic receptors (i.e., betaadrenergic agonists) produce
bronchodilation and can be used to prevent or inhibit airway obstruction in bronchospastic diseases
Beta-adrenergic drugs can be administered orally, subcutaneously, or by inhalation.
Another method of inhaling beta agonists is through a nebulizer. These devices mix the drug with air to form a
fine mist that is inhaled through a mask, thus reaching the lungs over a more prolonged period (10 minutes).
23. Beta-Adrenergic Agonists
Adverse Side Effects
Prolonged use of beta-2 drugs may also cause tolerance; the dose must be increased to achieve
therapeutic effects when this occurs
With prolonged or excessive use, inhaled adrenergic agonists may actually increase bronchial
responses to allergens and other irritants
Adrenergic agonists that also stimulate beta-1 receptors may cause cardiac irregularities if they
reach the myocardium through the systemic circulation.
Similarly, stimulation of CNS adrenergic receptors may produce symptoms of nervousness,
restlessness, and tremor.
24. Xanthine Derivatives
These drugs may enhance bronchodilation by inhibiting the phosphodiesterase (PDE)
enzyme located in bronchial smooth-muscle cells.
PDE breaks down cAMP; inhibiting this enzyme results in higher intracellular cAMP
cAMP is the second messenger that brings about respiratory smooth-muscle relaxation and
By inhibiting PDE, theophylline can prolong the effects of this second messenger and
25. Xanthine Derivatives
Theophylline may likewise help produce bronchodilation by other mechanisms, such as inhibition of intracellular calcium
release and stimulation of catecholamine release.
Adverse Side Effects
irritability, and restlessness
To prevent toxicity, the dosage should be individualized for each patient, using the lowest possible dose
27. Anticholinergic Drugs
The lungs receive extensive parasympathetic innervation via the vagus nerve.
The efferent fibers of the vagus nerve release acetylcholine onto respiratory smooth-muscle
cells, which contain muscarinic cholinergic receptors.
When stimulated, these receptors mediate bronchoconstriction.
Consequently, drugs that block muscarinic cholinergic receptors prevent acetylcholine-
induced bronchoconstriction, thus improving airflow in certain types of bronchospastic
28. Anticholinergic Drugs
Adverse Side Effects
Systemic side effects associated with atropine include dry mouth, constipation, urinary
retention, tachycardia, blurred vision, and confusion
Glucocorticoids (also known as corticosteroids) inhibit the inflammatory response in several
These drugs directly affect the genes and transcription factors that produce inflammatory
As a result, the drugs inhibit the production of proinflammatory products (cytokines
prostaglandins, leukotrienes, and so forth) while increasing the production of anti-inflammatory
Glucocorticoids also reverse the increase in vascular permeability and inhibit the migration of
neutrophils and monocytes typically occurring during the inflammatory response
Adverse Side Effects
and muscle wasting
retardation of growth in children,
aggravation of diabetes mellitus, and hypertension