1. Chapter 32 Airway Pharmacology

2. Objectives
• Analyze three phases that constitute the course of drug action from dose to effect. • Describe classes of drugs that are delivered via the aerosol route. • Compare mode of action, indications, and adverse effects that characterize each major class of aerosolized drug. • Compare available aerosol formulations, brand names, and dosages for each specific drug class. • Select the appropriate drug class for a given patient or clinical situation. • Assess the outcomes for each class of aerosol drug therapy.
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3. Principles of Pharmacology
The drug administration phase
The method by which a drug is made available to the body
Aerosol therapy is the most common route for drug administration to the pulmonary patient.
The most common devices used to administer inhaled aerosols are the MDI, small-volume nebulizer, and dry-powder inhaler.
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4. Principles of Pharmacology (cont.)
The drug administration phase (cont.)
The advantages of inhaled aerosols are
Can use smaller doses as compared to the systemic route
Onset of drug is rapid
Delivery is to the specific organ needing treatment
Less systemic side effects
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5. Principles of Pharmacology (cont.)
The pharmacokinetic phase
Describe the time course and disposition of a drug in the body based on its absorption, distribution, metabolism, and elimination.
Aerosols made up of medications that are fully ionized have little or no systemic side effects (e.g., ipratropium).
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6. Principles of Pharmacology (cont.)
The pharmacodynamic phase
Describe the mechanisms of drug action by which a drug molecule causes its effects in the body
Drug effects are caused by combination of a drug with a matching receptor.
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7. Principles of Pharmacology (cont.)
Airway receptors and neural control of the lung
Sympathetic (adrenergic) and parasympathetic (cholinergic) receptors are in the lung.
The neurotransmitter in the sympathetic system is norepinephrine (epinephrine).
The neurotransmitter in the parasympathetic system is acetylcholine.
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8. Principles of Pharmacology (cont.)
Airway receptors and neural control of the lung
(cont.)
Adrenergic: drug that stimulates a receptor responding to norepinephrine or epinephrine
Antiadrenergic: drug that blocks a receptor for norepinephrine or epinephrine
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9. Principles of Pharmacology (cont.)
Airway receptors and neural control of the lung (cont.)
Cholinergic: drug that stimulates a receptor for acetylcholine
Anticholinergic: drug that blocks a receptor for acetylcholine
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10. Adrenergic Bronchodilators
Indications for use
Indication for short-acting agents
For relief of acute reversible airflow obstruction
Indication for long-acting agents
For maintenance bronchodilation in patients with obstructive lung disease
Indication for racemic epinephrine
To reduce airway swelling after extubation or with acute upper airway inflammation from croup
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11. Adrenergic Bronchodilators (cont.)
Mode of action and effects
-Receptor stimulation: causes vasoconstriction and a vasopressor effect
1-Receptor stimulation: causes increased heart rate and heart contractility
2-Receptor stimulation: relaxes bronchial smooth muscle, stimulates mucociliary activity
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12. Adrenergic Bronchodilators (cont.)
Adverse effects
Older adrenergic agents such as isoproterenol commonly caused tachycardia, palpitations, and nervousness.
Newer 2-selective agents are safe, with tremor as the primary side effect.
Tolerance to the drug may occur.
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13. Adrenergic Bronchodilators (cont.)
Assessment of bronchodilator therapy
Based on the indication(s) for the aerosol agent
Vital signs, breath sounds, and breathing pattern should be evaluated before and after treatment.
The patient’s subjective response is important to evaluate.
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14. Adrenergic Bronchodilators (cont.)
Indications for use
Indication for anticholinergic bronchodilator
Indicated for maintenance bronchodilator therapy for COPD patients
Indication for combined anticholinergic and -agonist
COPD patients
Asthma patients
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15. Adrenergic Bronchodilators (cont.)
Mode of action
These agents act as competitive antagonists for acetylcholine on airway smooth muscle.
Adverse effects
Ipratropium bromide and tiotropium bromide have few systemic side effects since they are fully ionized and are not absorbed.
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16. Adrenergic Bronchodilators (cont.)
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17. Mucus-Controlling Agents
N-Acetyl-L-cysteine (NAC)
Given by aerosol or direct tracheal instillation
Given to reduce accumulation of airway mucus
May cause bronchospasm due to its irritating side effects
Dornase alfa
Indicated for the management of cystic fibrosis
May cause voice alteration, pharyngitis, rash, or chest pain
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18. Mucus-Controlling Agents (cont.)
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19. Inhaled Corticosteroids
Indications and purposes
Orally inhaled preparations are used for antiinflammatory maintenance therapy of persistent asthma and severe COPD.
The use of nasal steroids is for control of allergic and nonallergic rhinitis.
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20. Inhaled Corticosteroids (cont.)
Mode of action
Lipid-soluble drugs that act on intracellular receptors
Full antiinflammatory effects require hours to days.
Will not provide immediate relief of dyspnea from airways obstruction
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21. Inhaled Corticosteroids (cont.)
Adverse effects
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22. Inhaled Corticosteroids (cont.)
Assessment of drug therapy
Use strategies for assessment similar to those used for evaluation of bronchodilators.
In addition
Make sure patient understands the importance of consistent use and not to use it as a rescue drug.
Instruct patient in the use of a peak flowmeter.
Assess patient for side effects.
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23. Nonsteroidal Antiasthma Drugs
A growing class of drugs for the treatment of asthma
Three types exist
Comolyn-like agents (cromolyn, nedocromil sodium)
Antileukotrienes (zafirlukast, zileuton)
Monoclonal antibodies or anti-IgE agents (omalizumab)
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24. Nonsteroidal Antiasthma Drugs (cont.)
Indications for use
Used for prophylactic management (control) of mild to moderate persistent asthma
May be used as an alternative to steroids in patients with persistent asthma symptoms
Offer no benefit for acute airways obstruction in asthma
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25. Nonsteroidal Antiasthma Drugs (cont.)
Adverse effects
Cromolyn-like agents
- Considered extremely safe
Antileukotriene agents
- Headache, dyspepsia, liver enzyme elevation
Omalizumab
- Injection site reaction, viral infections
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26. Nonsteroidal Antiasthma Drugs (cont.)
Assessment of drug therapy
Strategies similar to those used to assess initial bronchodilator therapy
Clinician should verify that the patient understands that these medications are controller drugs and not rescue agents.
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27. Aerosolized Antiinfective Agents
Pentamindine isethionate
Has been used in the past for the treatment of Pneumocystis carinii pneumonia (PCP)
Due to limited efficacy, pentamindine is no longer recommended for PCP treatment
Common side effects include cough, bronchospasm and wheezing, dyspnea, etc.
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28. Aerosolized Antiinfective Agents (cont.)
Ribavirin
An antiviral agent used in the treatment of severe lower respiratory tract infections caused by respiratory syncytial virus (RSV)
Administration of the aerosol requires the use of a small particle aerosol generator (SPAG).
Cost-effectiveness continues to be debated.
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29. Aerosolized Antiinfective Agents (cont.)
Ribavirin (cont.)
Adverse effects
Skin rash
Eyelid erythema
Conjunctivitis
Patients and practitioners who are pregnant should not be exposed to ribavirin.
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30. Aerosolized Antiinfective Agents (cont.)
Inhaled tobramycin
Intended to manage chronic infection with P. aeruginosa in
patients with cystic fibrosis
Side effects with the inhaled route are usually minimal and include voice alteration and tinnitus.
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31. Aerosolized Antiinfective Agents (cont.)
Colistimethate sodium
An antibiotic used to treat sensitive strains of gram-negative bacilli, particularly P. aeruginosa
The most common side effect seen with the aerosol route is bronchospasm.
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32. Aerosolized Antiinfective Agents (cont.)
Inhaled zanamivir
An inhaled powder
Indicated for the treatment of uncomplicated acute illness due to influenza virus in adults and children at least 7 years of age
Can cause bronchospasm and allergic reactions
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33. Aerosolized Antiinfective Agents (cont.)
Use of aerosolized amphotericin B
May be used in lung transplantation patients to prevent or treat atypical infection
The aerosolized route reduces the risk of renal damage.
Can cause nausea, vomiting, and bronchospasm
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34. Inhaled Pulmonary Vasodilators
Nitric oxide (INOmax)
Indicated for the treatment of neonates (<34 weeks) with hypoxic respiratory failure and pulmonary hypertension
It relaxes vascular smooth muscle in the pulmonary vasculature.
The most common side effect is hypotension.
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35. Inhaled Pulmonary Vasodilators (cont.)
Iloprost
Used in the treatment of pulmonary hypertension
Administered with the I-neb or Prodose nebulizer
Acts by dilating the pulmonary vasculature
Side effects include headache and increased cough
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36. Antidiabetic Agents Exubera is an inhaled insulin.
Used to control hyperglycemia in diabetics
Should not be used by patients who smoke
Potential side effects include cough, dyspnea, pharyngitis, increased sputum, and epistaxis.
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