Chapter 32 Airway Pharmacology

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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). Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

Adrenergic Bronchodilators (cont.) Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

Mucus-Controlling Agents (cont.) Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

Inhaled Corticosteroids (cont.) Adverse effects Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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) Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.

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. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc.