This document discusses several classes of respiratory drugs including antitussives, decongestants, antihistamines, mucolytics and expectorants, bronchodilators, and anti-inflammatory drugs. It describes the mechanisms of action, indications for use, routes of administration, and potential adverse effects of drugs from each class. The classes covered include cough suppressants, nasal decongestants, antihistamines, mucus-thinning and cough-loosening drugs, beta-agonists, xanthines, anticholinergics, glucocorticoids, and cromones.

1. D R . M A R I A I D R E E S P T
M S ( R I U )
D P T ( T U F )
Respiratory Drugs

3. Antitussives
 suppress coughing associated with the common cold
and other minor throat irritations.
 When used to treat cold and flu symptoms, these
drugs are often combined with aspirin or
acetaminophen.
 Recommended for short-term use in relieving
symptomatic coughing.
 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.

4.  codeine and similar opiate derivatives suppress the
cough reflex by a central inhibitory effect.
Adverse effects:
 Sedation.
 Dizziness
 Gastrointestinal upset

6. Decongestants
 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

8.  May be taken systemically or applied locally to the
nasal mucosa via aerosol sprays
 Can mimic the effects of increased sympathetic
nervous system activity, and can cause serious
cardiovascular and central nervous system (CNS)
excitation.
 Excessive use or abuse should therefore be
avoided.

9. Adverse effects
 Headache
 Dizziness
 Nervousness
 Nausea
 Cardiovascular irregularities (increased blood
pressure, palpitations)
 These effects become more apparent at higher doses
and during prolonged or excessive drug use

10. Antihistamines
 Used for reasons ranging from sedation to the
treatment of parkinsonism.
 One of the most common applications of
antihistamines, however, is the treatment of the
respiratory allergic response to seasonal allergies
(hay fever, and so forth) and other allergens.

11.  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 reactions.
 Histamine exerts its effects on various cells
through four primary receptor subtypes: the H1,
H2, H3, and H4 receptors.

12.  Antihistamines are drugs that specifically block the
H1 subtype of histamine receptors; that is, the
effects of histamine during allergic reactions,
respiratory infections 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.

13.  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

15. Adverse Effects
 Sedation
 Fatigue
 Dizziness
 Blurred vision
 Incoordination
 Gastrointestinal distress (nausea, vomiting)
 “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.

16.  “second-generation” antihistamines, however, do not
easily cross the bloodbrain barrier, and the risk of
sedation and other CNS side effects is reduced
substantially.
 These newer agents, also known as nonsedating
antihistamines, include cetirizine (Zyrtec),
loratadine (Claritin), desloratidine (Clarinex), and
fexofenadine (Allegra)

17. 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.

18.  The primary mucolytic drug currently in use is
acetylcysteine (Mucomyst, Mucosil)
MOA:
 This drug is thought to work by splitting the
disulfide bonds of respiratory mucoproteins, thus
forming a less viscous secretion.
 Decrease free-radical damage in the respiratory
tissues.

19. Adverse Effects
 Nausea,
 Vomiting,
 Inflammation of the oral mucosa (stomatitis),
 and rhinorrhea.
 Serious adverse effects are relatively rare.

20.  Guaifenesin is the only drug currently
acknowledged by the FDA
 The primary adverse effect associated with
guaifenesin is gastrointestinal upset
 Exacerbated if excessive doses are taken or if this
drug is taken on an empty stomach.

21. Drugs Used to Maintain
Airway Patency in Obstructive
Pulmonary Disease
 Primary goals is to prevent or reverse the bronchial
constriction and subsequent obstruction of the
airways
 By using bronchodilators (beta-adrenergic
agonists, xanthine derivatives, anticholinergics)
 and anti-inflammatory agents (glucocorticoids,
others).

22. 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., beta adrenergic agonists)
produce bronchodilation and can be used to
prevent or inhibit airway obstruction in
bronchospastic diseases.

23. Mechanism of action of beta agonists on respiratory smooth muscle.
Beta agonists facilitate bronchodilation by stimulating adenyl cyclase
activity, which in turn increases intracellular cyclic AMP production.
Cyclic AMP activates protein kinase, which appears to add an inhibitory
phosphate group to contractile proteins, thus causing muscle relaxation
and bronchodilation.

24.  Beta-2–selective agonists offer an advantage when
administered systemically because there is less
chance of side effects caused by stimulation of
other adrenergic receptors located on other tissues.
 Formoterol, Salmeterol are considered to be long-
acting beta-adrenergic agonists.

25.  Beta-adrenergic drugs can be administered orally,
subcutaneously, or by inhalation.
 Inhalation of these drugs is often the preferred method
of administration in treating respiratory disorders.
 Oral or subcutaneous administration is usually
associated with more side effects (reach the more distal
branches of the airway) .
 Several beta agonists are available in metered dose
inhalers (MDIs) for inhalation administration.
 Another method of inhaling beta agonists is through a
nebulizer
 Dry powder inhaler (DPI)
Method of Administration

27. Adverse Side Effects
 Airway irritation
 Prolonged used cause tolerance
 Cardiac irregularities
 Stimulation of CNS adrenergic receptors may
produce symptoms of
 nervousness,
 restlessness,
 and tremor.

28. Xanthine Derivatives
 Common xanthine derivatives include theophylline,
caffeine, and theobromine
 Found in various foods and beverages (tea, coffee,
soft drinks).
 Theophylline administered therapeutically to
produce bronchodilation in asthma and other forms
of reversible airway obstruction (bronchitis,
emphysema)
 Theophylline and caffeine are also potent CNS
stimulants

29. MOA
 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
concentrations.
 cAMP is the second messenger that brings about
respiratory smooth-muscle relaxation and
subsequent bronchodilation.
 By inhibiting PDE, theophylline can prolong the
effects of this second messenger and increase
bronchodilation

31. Method of Administration
 Administered Orally
Adverse Side Effects:
 Use of xanthine bronchodilators is the possibility of
toxicity.
 Theophylline-induced seizures

32. 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.

33.  Consequently, drugs that block muscarinic
cholinergic receptors prevent acetylcholine-
induced bronchoconstriction, thus improving
airflow in certain types of bronchospastic disease.
 In particular, anticholinergics are often the drugs
of choice in treating COPD.
 The primary factors that mediate
bronchoconstriction in emphysema and chronic
bronchitis appear to be increased vagal tone and
acetylcholine release.

34. Route of Administration
 The anticholinergic bronchodilators include
ipratropium and tiotropium, which are muscarinic
receptor blockers that are similar in structure and
function to atropine.
 Atropine use in respiratory conditions is usually
limited because it is readily absorbed into the
systemic circulation and tends to produce many side
effects.
 Tiotropium (Spiriva), ipratropium (Atrovent) by
aerosol inhaler

35. Adverse Side Effects
 Systemic side effects associated with atropine
include
 dry mouth,
 constipation,
 urinary retention,
 tachycardia,
 blurred vision,
 and confusion.

36. Glucocorticoids
 Inflammation appears to be a key underlying factor
in the exaggerated responsiveness of the respiratory
passages in asthma and other obstructive pulmonary
disorders.
 Glucocorticoids are used to control inflammation-
mediated bronchospasm and are undoubtedly the
most effective agents for controlling asthma

37. Routes of Administration
 administered intravenously
 For prolonged use, glucocorticoids are given orally
or by inhalation
Adverse Side Effects
 osteoporosis,
 skin breakdown,
 and muscle wasting
 retardation of growth in children,
 cataracts, glaucoma, hyperglycemia, aggravation of
diabetes mellitus, and hypertension.
 loss of adrenal function

39. Cromones
 Cromones such as cromolyn sodium (Intal,
Nasalcrom) and nedocromil sodium (Tilade) can
help prevent bronchospasm in people with asthma.
 Cromolyn and nedocromil are believed to prevent
bronchoconstriction by inhibiting the release of
inflammatory mediators such as histamine and
leukotrienes from pulmonary mast cells.

40. Adverse Side Effects
 Some irritation of the nasal and upper respiratory
passages
 Free of serious adverse reaction
 Treat mild persistent asthma

41. Leukotriene Inhibitors
 Leukotrienes are inflammatory compounds that are
especially important in mediating the airway
inflammation that underlies bronchoconstrictive
disease.
 leukotrienes are synthesized by the lipoxygenase
enzyme rather than by the cyclooxygenase enzyme
(Prostaglandin).

42.  Zileuton (Zyflo) inhibits the lipoxygenase enzyme,
thereby reducing the production of leukotrienes.
 Other drugs such as montelukast (Singulair) and
zafirlukast (Accolate) block the receptor for
leukotrienes on respiratory tissues

43. Adverse Side Effects
 Leukotriene inhibitors are safer
 Some hepatic impairment

44. Treatment of
Bronchial Asthma
 Bronchial smooth-muscle spasm
 Airway inflammation
 and mucous plugging of the airways

45. Long-Term Management of Asthma
 The use of glucocorticoids drugs are now used as
first-line agents in most patients
 these drugs directly reduce the inflammation that
underlies asthmatic disease
 Drugs that block leukotriene receptors (montelukast,
zafirlukast), or inhibit the formation of leukotrienes
(zileuton) can be extremely helpful in the long term
control of asthma.
 Beta-2 agonists are still used frequently as the
primary method of symptomatically treating
asthma attacks.

46.  Prolonged and excessive use of beta-2 agonists may
actually increase airway hyperresponsiveness, thus
increasing the risk of bronchoconstrictive attacks.

47. Treatment of Reversible
Bronchospasm in COPD
 Bronchospasm is often present in COPD—that is, in
chronic bronchitis and emphysema.
 Chronic bronchitis is a clinical diagnosis applied to a
long-standing inflammation of the bronchial tree.
 Emphysema is a pathologic condition marked by the
destruction of alveolar walls and enlargement of the
terminal air spaces.
 Anticholinergics (ipratropium, tiotropium) are typically
the first drugs used
 Theophylline can also be used as a bronchodilator in
COPD

48. Treatment of Respiratory
Problems in Cystic Fibrosis
 Cystic fibrosis essentially affects all the major
exocrine glands, resulting in very thick, viscous
secretions.
 These thickened secretions often form mucous plugs,
which obstruct major ducts in various glands and
organs

49. Treatment
 Bronchodilators
 Mucolytic and/or expectorant drugs
 NSAIDs
 Antibiotic
 Aerosol preparations that contain enzymes known as
deoxyribonucleases reduce the chance of atelectasis