Pharmacology

Respiratory Drugs
CICCONE CHAPTER 26
Respiratory tract review
- Purpose – mediate gas exchange between environment and bloodstream
◦ Humidifies and conditions inspired air
◦ Protects lungs from harmful substances
◦ Gas exchange between alveoli and pulmonary circulation

- Two primary groups of drugs discussed in this presentation;

◦ Drugs that treat acute and relatively minor problems – nasal congestion, coughing, seasonal
allergies, etc.
◦ Drugs that treat more chronic and serious airway obstructions – bronchial asthma, chronic
bronchitis, emphysema
Drugs that treat respiratory tract irritation
and control respiratory secretions
1. Antitussives Table 26-1 – Suppress coughing associated with cold, flu, and other minor throat
irritations.
◦ Often combined with aspirin or acetaminophen and/or other respiratory drugs.
◦ Short term use – preferably with dry cough, not productive (may prevent clearing secretions)
◦ Many OTC meds are not really strong enough to be effective.
◦ Toxic effects can occur with infants and young children because of inappropriate dosing and
overdose (in part because they are not effective at non-toxic doses)
◦ Codeine and similar opioid derivatives are the “classic” drugs in this class – suppress the
cough reflex.
◦ Nonopioid antitussives inhibit the irritant effects of histamine on the resp. mucosa, or by a
local anesthetic action on the respiratory epithelium.
◦ Adverse effects – sedation primary. Dizziness and GI upset possible. Chronic use of opioid
versions can lead to tolerance and dependence.
Drugs that treat respiratory tract irritation and control
respiratory secretions, cont.

2. Decongestants table 26-2– treat upper respiratory tract congestion and mucous
discharge from allergies, cold, infections, etc.
◦ Mostly alpha-1-adrenergic agonists (see chapter 20): bind to alpha-1 receptors on the
blood vessels of the nasal mucosa and stimulate vasoconstriction > dries up the
mucosal vasculature and decreases local congestion in nasal passages.
◦ Can be systemic use or local application via aerosol sprays
◦ Problematic use of ephedrine and pseudoephedrine in production of
methamphetamine
◦ Adverse effects – mimic effects of increased SNS activity, including cardiovascular and
CNS excitation, esp. with excessive use or abuse.
◦ Headache, dizziness, nervousness, nausea, cardiovascular irregularities (increased
BP, palpitations)
Drugs that treat respiratory tract irritation and control
respiratory secretions, cont.
3. Antihistamines table 26-3– Treatment of respiratory symptoms caused by viral
infections like cold and seasonal allergies. Can also be used for sedation, treating PD, etc.
◦ Histamine is an endogenous chemical that regulates certain physiological functions and
various hypersensitivity (allergic) reactions.
◦ Affects 4 primary receptor subtypes = H1 – H4 . Allergies mediated through H1 receptors on
vascular, respiratory, and other tissues. H4 may be important in mediating inflammation is
conditions like asthma, allergic rhinitis, and other inflammation.
◦ Antihistamines block H1 receptors > decrease nasal congestion, mucosal irritation and
discharge, allergy-related conjunctivitis (rhinitis and sinusitis)
◦ Used as an adjunct with asthma
◦ Adverse effects – First generation drugs cross BBB resulting in sedation, fatigue, dizziness,
blurred vision, and incoordination. Some risk of serious cardiovascular side effects. GI distress
is also common. New “nonsedating antihistamines” (e.g. Zyrtec, Claritin, Clarinex, Allegra) are
more selective and have fewer side effects.
 Drugs that treat respiratory tract irritation and control
respiratory secretions, cont.
4. Mucolytics and expectorants – decrease viscosity of respiratory secretions, facilitate the
production and ejection of mucus – with goal of preventing clogged respiratory passages.
◦ Treat cold, pneumonia, chronic disorders like emphysema and chronic bronchitis.
◦ Often taken in combination with previously mentioned drugs
◦ Actual benefit is questionable, and varies with patient and problem
◦ Mucolytic – acetylcysteine (Mucomyst, Mucosil) – probably works by splitting bonds of respiratory
proteins > less viscosity. Also has antioxidant effects; may help prevent free radical damage.
◦ Is also used to prevent liver damage in acetaminophen overdose
◦ Administration – inhalation or through tracheostomy
◦ Adverse effects – nausea, vomiting, inflammation of oral mucosa
◦ Expectorant – Guaifenesin – Increases the production of respiratory secretions > encourages
ejection of phlegm and sputum.
◦ Mechanism of action uncertain
◦ Administration orally – usually as syrup/elixir; often in combination with other drugs
◦ Adverse effect – GI upset – worse with excessive dose or on empty stomach
Drugs used to maintain airway patency
in obstructive pulmonary disease
These drugs are used to treat bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD)
(chronic bronchitis and emphysema). Symptoms of these disorders include bronchospasm, airway
inflammation, mucus plugging of airways. Treatment goal is to generally to prevent the constriction
and obstruction with bronchodilators and anti-inflammatories.
1. Beta-adrenergic Agonists table 26-4– Stimulation of Beta-2 receptors on respiratory smooth
muscle cells> relaxation of bronchiole smooth muscle (Fig. 26-1 and next slide)
◦ Some drugs are more or less selective for alpha and certain beta receptors. Less side effects if beta-2
receptor specific, or if administered by inhaler to target respiratory tissues.
◦ Administration can be BID or daily, depending on drug. Can be used orally, sub-Q, or by inhalation.
◦ Oral or sub-Q may reach distal branches of airway better, esp. in a constricted airway situation
◦ Inhalation can use metered-does inhalers (MDIs) – requires coordination of inhalation with administration
◦ Inhalation can be through a mask with mist nebulizer
◦ Inhalation with dry powder inhaler (DPI)
 Beta-adrenergic agonists, cont.

Adverse effects –
o With prolonged or excessive use, may
increase bronchial responses to allergens
and irritants.
o Prolonged use can cause tolerance.
o Combining with other drugs may help
prevent over use.
o Other effects depend on selectivity and
route of administration and are
infrequent; cardiac irregularities,
nervousness, restlessness, tremor

Fig. 26-1 Probable method of beta-adrenergic action

Drugs used to maintain airway patency in
obstructive pulmonary disease, cont.
2. Xanthine Derivatives fig. 26-2 – group of chemically similar compounds, including theophylline,
caffeine, and theobromine.
◦ Found in various foods and beverages
◦ Theophylline and other theophylline derivatives used for bronchodilation in asthma and other airway
obstructions
◦ Theophylline and caffeine are also potent CNS stimulators
◦ Actions for Theophylline–
◦ ? May inhibit phosphodiesterase (PDE) enzyme in bronchial smooth muscle cells > higher intracellular
cAMP > prolongs cAMP’s muscle relaxation and bronchodilating properties.
◦ ? May decrease function of inflammatory cells and inhibit the production of inflammatory mediators> anti-
inflammatory effect. (May be the more significant effect)
◦ ? May be an adenosine antagonist > blocks its ability to stimulate airway contraction
◦ ? Possible other mechanisms – inhibition of intracellular calcium release, stimulation of catecholamine
release, activation of enzymes that promote the anti-inflammatory effects of glucocorticoids
Xanthine derivatives, cont.
Theophylline, cont.
◦ Administration – oral primarily. If not tolerated can to rectal or injection. Sustained release
tablets available that allow 1 to 2x daily use.
◦ Adverse effects –
◦ Possible toxicity – early signs include nausea, confusion, irritability, restlessness. Progress to
serious – cardiac arrhythmias, seizures; life threatening, esp. with long term use
◦ Increased risk with liver disease, CHF, age over 55, infections (e.g. pneumonia), interactions
with some other drugs
◦ Always use lowest possible dose

3. Anticholinergic Drugs
◦ Action – block muscarinic cholinergic receptors > prevents acetylcholine-induced
bronchoconstriction that occurs from vagus nerve innervation and other non-neural cell release
◦ Drug of choice in COPD because increased vagal tone and subsequent increased acetylcholine
are factors in these diseases, causing constriction, inflammation, increased mucus production,
chronic cough, airway cell proliferation. Mechanism of asthma is different, so not used as much,
but can help in acute moderate to severe asthma attacks.
Anticholinergics, cont.
◦ Administration-
◦ Ipratropium (Atrovent) – administered by inhaler 3-4 x/day; better local absorption
and fewer side effects
◦ Tiotropium (Spiriva) – longer lasting, inhaled once daily, and may be better at
improving pulmonary function
◦ Adverse effects – dry mouth, constipation, urinary retention, tachycardia,
blurred vision, and confusion with atropine. Less with the inhaled drugs above
because they are not as readily absorbed into the bloodstream
 Drugs used to maintain airway patency in obstructive
pulmonary disease, cont.
4. Glucocorticoids (corticosteroids) table 26-6– used to reduce inflammation-mediated
bronchospasm. Most effective agents for controlling asthma
◦ Actions –
◦ affect genes and transcription factors that produce inflammatory components> inhibit production of
proinflammatory products and increase production of anti-inflammatory proteins
◦ Affect cell membrane receptors that regulate activity of inflammatory cells
◦ Administration – IV in acute episodes. Oral or inhalation for prolonged use; inhaled preferred because
of fewer side effects and direct administration to respiratory mucosa. Rinse mouth after oral drug to
prevent oral mucosa irritation
◦ Adverse effects -
◦ Osteoporosis, skin breakdown, muscle wasting with prolonged systemic use.
◦ Retardation of growth with children, cataracts, glaucoma, hyperglycemia, aggravation of DM, and
hypertension
◦ Can develop resistance (esp. with COPD), and develop adrenal suppression
◦ Effects are minimal when inhaled versions are used and doses kept as low as possible
Drugs used to maintain airway patency in obstructive
pulmonary disease, cont.
5. Cromones (e.g. cromolyn sodium [Intal, Nasalcrom])- used for bronchospasm is
asthma. NOT bronchodilators and will not reverse bronchoconstriction. Have to be
taken prior to onset of bronchoconstriction, so use prophylactically to prevent
asthma attacks that are initiated by specific activities (exercise, pet, pollen, etc.).
Nonprescription form helps with seasonal allergies.
◦ Regular use may decrease airway hypersensitivity so attack incidence decreases
◦ Action – inhibit release of inflammatory mediators (e.g. histamine, leukotrienes)
from pulmonary mast cells
◦ Administration – inhaled with MDI or nebulizer
◦ Adverse effects – Irritation of upper respiratory passages. With very few side
effects may be used with children or others who don’t tolerate other drugs well.
 Drugs used to maintain airway patency in obstructive
pulmonary disease, cont.

6. Leukotriene Inhibitors - e.g. zileuton (Zyflo) -

decrease the effects or the synthesis of the
leukotriene inflammatory mediators that cause
bronchoconstriction.
◦ Are therefor rather selective.
◦ May be combined with other drugs like
steroids or beta agonists to treat asthma
and COPD. Enhance anti-inflammatory
effects of glucocorticoids
◦ Adverse effects – rare cases of toxicity;
hepatic impairment https://commons.wikimedia.org/wiki/File:Blaus
en_0620_Lungs_NormalvsInflamedAirway.png
Treatment of Bronchial Asthma
Pathophysiology
◦ Bronchial smooth-muscle spasm, airway inflammation, mucous plugging of airways
◦ Exaggerated bronchoconstrictor response to certain stimuli. Can be triggered by; allergens, pollen,
drugs, chemicals, cold, exercise, stress, viral infections, etc.
◦ Structural changes in the airway > increased bronchoconstriction
◦ Initiated by airway inflammation > release of chemical mediators (prostaglandins, leukotrienes,
bradykinin, histamine, platelet activating factor > irritation of respiratory epithelium and stimulation
of contraction of bronchiole smooth muscle
Long term management (table 26-7)
◦ Glucocorticoids (preferably inhaled) to address the inflammation
◦ May be combined with a long-acting beta-2 agonist for bronchodilation and to keep the steroid
dose needed minimized
◦ For asthma attacks, can use short-acting beta-2 agonist – “rescue” therapy/MDI. Should not be used
excessively
Treatment of asthma, cont.
Long term management, cont.
◦ May use leukotriene inhibitors/blockers. Esp. with exercise-induced asthma, or when patient
doesn’t respond to steroids, or combined with steroids to lower steroid dose
◦ Theophylline used sparingly for bronchodilation because of toxic side effects. Can be
combined with steroids to minimize dose of each.
◦ Can add- cromolyn sodium and antihistamines if needed.
◦ Avoiding triggers once identified
◦ Aerobic conditioning

Bottom line – combinations of drugs specific to patient needs and with effort to minimize side
effects. Takes ongoing management/adjustment.
Treatment of Reversible bronchospasm in COPD
COPD – Chronic Bronchitis (CB) and Emphysema (“blue bloaters vs. pink puffers”)
◦ CB = long-standing inflammation and remodeling of the bronchial tree
◦ Emphysema = pathologic destruction of alveolar walls and enlargement of terminal air spaces
◦ Drug therapy goal – maintaining airway patency and preventing airflow restriction
◦ Anticholinergics often first drug, and/or beta-2 agonists, or a combination of these two
◦ Theophylline can be used if there is a lack of response to other drugs, and to add its anti-
inflammatory effects
◦ Controversial use of steroids – maybe combined with Beta-2 agonists in severe cases
Treatment of Respiratory Problems in Cystic Fibrosis
- CF is one of the most common hereditary disease in Caucasian population (1 in 2000-4000 births). Life span
now into 30’s-40’s. No cure at this time.
◦ Affects all exocrine glands> thick, viscous secretions and mucous plugs (e.g. bile duct, bronchioles)
◦ Bronchiole plugging leads to things like pneumonia, bronchiectasis, pulmonary fibrosis, and pulmonary
infections (e.g. straph. And pseudomonas).
◦ * Is often the primary health threat for these individuals
- Drug management – maintenance of open airways
◦ Bronchodilators, mucolytic/expectorant drugs to limit formation of plugs
◦ Glucocorticoids to limit inflammation, but limited because of side effects (can’t use inhaled because of
thick mucous lining)
◦ Use of NSAIDs to control inflammation
◦ Use of antibiotics as needed for infections
◦ Use or aerosol deoxyribonucleases to break down excessive DNA in airway lumen from break down of
inflammatory cells> decrease in these causing changes in viscosity of secretions> less atelectasis and
infection
◦ ? Eventually gene therapy to replace defective gene causing the problem
-Respiratory Hygiene is key
◦ Postural drainage, breathing exercises, general exercise, good nutrition, maintenance of good body weight.
Rehab. implications
1. Helping with respiratory hygiene – postural drainage, breathing exercise,
encourage cough/expectoration, in some places suctioning. Chest PT 10 – 60
minutes after nebulizer treatment?
◦ Coordination with respiratory therapy and team.

2. Awareness of patients susceptible to bronchospastic attacks.

◦ Always have portable meds with during therapy

3. Awareness of drug side effects – esp. cardiac side effects. Early recognition of
toxicity
4. Monitor for side effects for those on steroids – skin breakdown, bones and
muscle/tendons susceptible to overstress