Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 20 Drugs Affecting the Respiratory System

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Asthma and Chronic Obstructive Pulmonary Disease (COPD) Asthma—chronic disease with abnormal reactivity of the bronchioles to triggers such as pollen, exercise, dust mites, and cigarette smoke COPD—chronic bronchitis and emphysema result in loss of elasticity of lungs and airway constriction

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Bronchodilators Selective β 2 -agonists –Provide symptomatic relief of wheezing and chest tightness –Do no prevent asthma attacks

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications Selective β 2 -agonists selectively relax smooth muscle surrounding bronchioles. Albuterol is fast-acting treatment of choice for symptoms of asthma occurring once or twice a week. For persistent asthma, maintenance treatment with long-acting β 2 -agonists, such as formoterol and salmeterol, can sometimes be beneficial.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications (cont’d) COPD treatment includes bronchodilators with beta-agonists and anticholinergic bronchodilators (ipratropium and tiotropium). Actions include bronchodilation, relief of symptoms, and improved quality of life on a temporary basis.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Systemic circulation via mouth or injection Direct local administration via inhalation, when possible, is preferred route due to direct delivery to airways, less systemic absorption, and fewer systemic side effects.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration (cont’d) Metered dose inhaler (MDI)—small pressurized canister containing drug and mouthpiece for administration of set dose of drug at each activation Nebulizer—device uses small compression pump to convert drug solution into a mist inhaled through a mouthpiece

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Side Effects Selective β 2 in repeated use or high doses can have deleterious cardiac effects such as fatal arrhythmias; jitteriness and increased heart rates are fairly common. Beta-agonists can produce adverse CNS effects including anxiety, fear, tension headache, and tremor.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects (cont’d) Dry mouth is common with ipratropium and tiotropium. Tiotropium occasionally causes urinary retention and constipation. Dry powder inhaler use is associated with throat irritation and coughing. Use of a spacer with MDI can reduce associated bad taste and irritation.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Become familiar with respiratory drug delivery systems and equipment to provide customers with sound information. Encourage inexperienced patients to look over inhaler instructions while still in the pharmacy.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Review The device that uses a small compressor pump for aid in the inhalation process is known as a: A) MDI B) Nebulizer C) Mister D) Spacer

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer B) Nebulizer A nebulizer uses a small compressor pump to convert the drug solution into a mist that the patient inhales through a mouthpiece.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Respiratory Corticosteroids Glucocorticoids are endogenous hormones synthesized from cholesterol by the adrenal glands. In humans, the most important of these hormones is cortisol. Synthetic derivatives of cortisol are used for their anti-inflammatory effects in a variety of diseases.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Inhaled Corticosteroid Actions and Indications Indicated for prevention of acute exacerbation of asthma Inhibit many of the cells involved with inflammation in the bronchi and bronchioles and reduce airway edema Peak effects take several weeks; therefore, not effective for acute asthma attacks

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications (cont’d) As nasal spray, corticosteroids are also effective for allergic rhinitis, reducing congestion and itching within a few hours to days.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Intravenous Oral Inhalation Nasal spray

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects Serious side effects are much less likely and less severe when medications are inhaled. Long-term use of inhaled corticosteroids at maximal doses can cause minor suppression of cortisol production in the body. Oral candidiasis

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Use special caution when dispensing inhalers available in different strengths. Apply “shake well” label to MDIs. Dry powder inhaler devices are not shaken before use. Apply auxiliary labels to include MDI use, rinse mouth after using, and cleaning mouthpiece after every use.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Review Dry powder inhalers should be shaken well to activate before administering. A) True B) False

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer B) False Dry powder inhaler devices are not shaken before use.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Alternative Pulmonary Anti-Inflammatory Drugs The mast cell stabilizers cromolyn and nedocromil are first-line drugs for long- term prevention of asthma in place of steroids or in addition to the regimen. The leukotriene modifiers montelukast, zafirlukast, and zileuton allow reduction of doses of inhaled corticosteroids in some patients with chronic asthma.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications Cromolyn and nedocromil inhibit release of histamine, leukotrienes, and other inflammatory chemicals by mast cells and other granulocytes. Mast cell stabilizers are indicated for long-term management of asthma. Cromolyn is indicated for treatment of allergic rhinitis and has been used off- label for chronic urticaria (hives).

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Cromolyn and nedocromil are administered via inhalation for asthma. Cromolyn is available in MDI and nebulizer as well as nasal spray for allergic rhinitis. Nedocromil is available as MDI only. Leukotriene inhibitors are administered orally.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects Mast cell stabilizer side effects –Throat irritation, cough, dry mouth, and unpleasant taste in the mouth –Not absorbed from the respiratory tract; there are no systemic side effects attributable

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects (cont’d) Leukotriene inhibitor side effects –Headache –GI upset –Hepatotoxicity, eosinophilia, and pain in rare instances

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Label MDIs with auxiliary “shake well” label. Label zafirlukast to be taken on empty stomach. Instruct patients to take medication as ordered, even when symptom free.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Methylxanthine Derivatives Coffee, tea, and chocolate all contain methylxanthine derivates known to possess bronchodilatory effects. Theophylline and the related drug aminophylline are the methylxanthine derivatives most often used for COPD and sometimes asthma.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications Bronchodilator and minimal anti- inflammatory effects in airways Indicated for treatment of COPD, after use of anticholinergic and beta-agonist drugs Indicated for asthma treatment; generally reserved for difficult-to- control asthma and when alternatives have failed

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Theophylline and its derivatives are available in extended-release tablets and capsules and rectal and injectable forms. For IV administration, aminophylline is preferred. Elimination is extremely variable from patient to patient, and serum levels are monitored to avoid toxicity.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects Due to narrow therapeutic index, difficulty in dosing, individual response to drugs, and side effects, use of theophylline and related drugs is waning. Side effects can include headache, irritability, nausea, vomiting, CNS stimulation leading to seizures, hypotension, and cardiac arrhythmias.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Be aware of dosing differences between theophylline products. Be aware that many drugs and additives are incompatible with aminophylline intravenous solutions.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Allergic Rhinitis, Coughs, and Colds Rhinitis—inflammation of mucous membranes of the nose –Treatment includes antihistamines, decongestants, and intranasal application of corticosteroids. –Preventative measures, such as environmental air filters, can be useful.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Allergic Rhinitis, Coughs, and Colds (cont’d) Cough—a natural response to airway irritation and aids process of clearing foreign material Coughs can be symptomatic of asthma, bronchitis, or simple viral infections.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Antihistamines Reversible antagonists of the H 1 receptor Prevent typical effect of histamine stimulation at this receptor First-generation antihistamines are nonselective and can activate H 1 receptors in the CNS, which accounts for their sedating effects.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Antihistamines (cont’d) Second-generation, “nonsedating” antihistamines are selective for peripheral H 1 receptors. Indicated for allergic reactions, including hives and itching of eczema Diphenhydramine remains the standard antihistamine to which other drugs are compared.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Because of the variety of indications for use, antihistamines are available in the following formulations: –Oral –Injectable –Rectal –Topical

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects Most common side effect of nonspecific antihistamines is sedation. The second-generation antihistamine cetirizine is most likely to cause minimal drowsiness. Lower antihistamine doses are recommended for elderly patients. Children may exhibit paradoxical response.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Patients should be urged to read package labeling for warnings and contraindications of OTC antihistamines. Auxiliary labels should be affixed to prescription warning of potential sedation and discouraging alcohol consumption. Promethazine suppositories are stored in refrigerator and labeled accordingly.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Cough Suppressants, Decongestants, and Expectorants Colds are the most common form of infection. Patients can be aided with drugs indicated for short-term treatment of symptoms accompanying colds and other upper respiratory infections.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions and Indications Pseudoephedrine, phenylephrine, oxymetazoline, and others are alpha- agonists useful as nasal decongestants. Opiate cough suppressants, including codeine, decrease the sensitivity of the cough centers in the CNS. Expectorants such as guaifenesin promote the removal of sputum from the lungs.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Review A natural way for the body to clear foreign material is through coughing. A) True B) False

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer A)True Coughing is a natural response to airway irritation and aids the process of clearing foreign material.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Administration Nasal decongestants are available as nasal sprays or drops. Pseudoephedrine is most universally used and is available in tablets, capsules, chewable tablets, extended- release tablets, pediatric liquid, and infant drops. Dextromethorphan is available in tablets, capsules, and liquids.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects Rebound congestion can occur with nasal decongestants. Elevation of blood pressure can occur with oral decongestant; people with glaucoma and cardiac disease and patients taking MAO inhibitors should avoid systemic decongestants. Nausea and vomiting may occur with dextromethorphan or guaifenesin.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Side Effects (cont’d) Both dextromethorphan and pseudoephedrine carry some risks of abuse and, by federal law, are stored behind the prescription counter. –Dextromethorphan can cause hallucinations when taken in extremely high doses. –Pseudoephedrine can be converted to the stimulant methamphetamine.

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Tips for the Technician Any narcotic antitussive should be properly labeled with auxiliary warning instructions regarding drowsiness, avoidance of operation of complex machinery, and avoidance of alcohol consumption. Any consumer questions regarding OTC preparations should be referred to the pharmacist.