Module 6 - Respiratory
N609

Nasal congestion and discharge
Sneezing; postnasal drip
Fullness and tenderness over the sinuses
Fever, headache
Malaise, myalgia
Sore throat, coughing
Full feeling around the eyes and ears

Human rhinovirus (most common)
Coronavirus
Respiratory syncytial virus
Influenza virus
Human parainfluenza virus
Human metapneumovirus
Adenovirus

What is the most common cause of upper respiratory infections?
A. Rhinovirus
B. Coronavirus
C. Respiratory syncytial virus
D. Influenza virus

A. Rhinovirus
Rationale: Acute infectious rhinitis, also known as the common cold, nasopharyngitis, rhinopharyngitis, or acute coryza, is caused by one of more than 200 viral types and most commonly involves rhinovirus. It is one of the most common infections and is usually minor and self-limiting.

Airborne transmission by small particles (droplets)
Airborne transmission by large particles
Direct contact

The most common method of diagnosis involves symptom evaluation.
Onset of common cold signs and symptoms occurs 1 to 2 days after viral infection and peaks in approximately 2 to 4 days.
A cough may persist following the resolution of other symptoms.
Symptoms consist primarily of clear nasal discharge, sneezing, nasal congestion, cough, low-grade fever (below 102 degF [38.9 degC]), scratchy or sore throat, mild aches, chills, headache, watery eyes, tenderness around the eyes, fullness in the ears, and fatigue.

Relief of symptoms
Reduction of the risk for complications
Prevention of spread to others

Brands
Oxymetazoline hydrochloride (Afrin, Mucinex Sinus, Neo-Synephrine, Vicks Sinex)
Phenylephrine hydrochloride (Neo-Synephrine, Sudafed PE, Afrin Childrens)
Pseudoephedrine (Sudafed)
Side effects
Palpitations, headaches, increased blood pressure, dizziness, gastrointestinal (GI) upset, tremor, insomnia

The most commonly available expectorant is guaifenesin (Antitussin, Mucinex, Robitussin). Some studies have shown this product to have limited advantage over increased fluid intake, and evidence regarding benefit is generally controversial (Fashner et al., 2012). Use of guaifenesin should generally not last beyond 1 week.
Side effects: drowsiness, headache, dizziness, GI upset.

Cough suppressants, such as dextromethorphan (Delsym) and benzonatate (Tessalon Perles), are available in oral preparations, including liquids, gels, capsules, lozenges, and sublingual strips, but studies have shown minimal benefit with the common cold (Fashner et al., 2012).
For some patients, these agents may reduce cough frequency and help achieve sleep; however, consistent benefit has not been demonstrated.
There is little evidence to favor the use of narcotic antitussives, such as codeine and hydrocodone, over other agents to relieve cough.

A practitioner is prescribing an antitussive for a patient with acute infectious rhinitis. What drug acts as an antitussive?
A. Oxymetazoline hydrochloride
B. Pseudoephedrine
C. Guaifenesin
D. Dextromethorphan

D. Dextromethorphan
Rationale: Cough suppressants (antitussives), such as dextromethorphan (Delsym) and benzonatate (Tessalon Perles), are available in oral preparations including liquids, gels, capsules, lozenges, and sublingual strips. Oxymetazoline hydrochloride and pseudoephedrine are decongestants. Guaifenesin is an expectorant.

Cyclooxygenase inhibitors, such as nonsteroidal antiinflammatory drugs (NSAIDs), inhibit prostaglandin secretions, which can reduce headache, malaise, myalgias, cough, and even sneezing.
Naproxen (Naprosyn, Aleve) is available as an oral tablet or suspension and is the NSAID of choice in the American College of Clinical Pharmacy guidelines because it does not impact viral shedding (Jacobs et al., 2013).

Local application of anticholinergic agents to the nasal mucosa inhibits vagally mediated reflexes by antagonizing the action of acetylcholine at the cholinergic receptor, thereby inhibiting secretions from the serous and seromucous glands lining the nasal mucosa.
The result is a decrease in nasal discharge and rhinorrhea.

Antihistamines should not be recommended as monotherapy for the treatment of cough and other cold symptoms, as they are ineffective. OK though if combining with decongestant.
Antihistamine-induced dryness may even exacerbate symptoms of congestion and cause upper airway obstruction by impairing the flow of mucus.
For symptoms of rhinorrhea and a feeling of fullness in the ears, first-generation antihistamines, such as diphenhydramine and chlorpheniramine, may be effective when combined with decongestants.

A practitioner is prescribing oral Benadryl for a 14-year-old patient who is diagnosed with chronic rhinosinusitis. What is the appropriate dosage?
A. 100 mg q6-12h
B. 25-50 mg q4-6h
C. 220 mg q8-12h
D. 20 mg/kg/d q8h or 25 mg

B. 25-50 mg q4-6h
Rationale: The recommended dosage for oral diphenhydramine (Benadryl) for patients 12 y is 25-50 mg q4-6h.

A limitless selection of combination products is available for the alleviation of cough and cold symptoms.
These products can often be difficult to recommend, as they contain multiple active ingredients, each associated with unique adverse drug events.
If recommending one of these products, it is important to ensure that there is an indication for each active ingredient, to avoid overmedicating the patient.

Rhinosinusitis is an upper respiratory tract infection (URI) characterized by inflammation of the mucous membranes that line the sinuses and nasal cavity causing nasal blockage, purulent discharge, and facial pain or pressure.
Sinusitis and rhinitis are unlikely to occur without inflammation of the nasal cavity membranes, so the term rhinosinusitis provides a better description of the inflammatory disease involving the URI.

Most cases of AVRS can be attributed to respiratory viruses including rhinovirus, influenza, and parainfluenza virus.
The most common pathogens involved in acute bacterial rhinosinusitis (ABRS) include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with the latter being the most common pathogen in pediatric cases.

Adequate rest and hydration
Elevating the head of the bed while sleeping
Use of a humidifier
Avoidance of environmental factors such as allergens, cigarette smoke, and pollution

The diagnosis of acute rhinosinusitis in adults at primary health care levels is based on the presence of two or more of the following hallmark symptoms: nasal congestion, nasal discharge, facial pain or headache, and anosmia (loss of smell).
For pediatric patients, cough replaces decreased sense of smell as one of the four hallmark symptoms.

The primary treatment goal is to restore sinuses to health.
Other goals include decreasing the duration and severity of symptoms, promoting appropriate use of antibiotic treatment, preventing complications and the progression from acute illness to chronic disease, and preventing the transmission of illness to other people.

Obtaining cultures is only recommended for patients who do not respond to first- or second-line treatment; therefore, management strategies will focus on the empiric treatment of ABRS.
Guidelines no longer recommend the regular use of macrolides, third-generation cephalosporins, or trimethoprim-sulfamethoxazole (Bactrim) for empiric treatment due to their high resistance rates with S. pneumoniae.

Amoxicillin, a beta-lactam antibiotic, inhibits synthesis of the bacterial cell wall by binding to one or more of the penicillin-binding proteins causing the bacteria to lyse.
Adding clavulanate to amoxicillin expands its spectrum of activity by inhibiting bacterial beta-lactamases that inactivate amoxicillin.

Doxycycline (Oracea, Vibramycin), a tetracycline antibiotic, binds with the 30S and possibly the 50S ribosomal subunit(s) of the bacteria, which inhibits protein synthesis resulting in bacteriostatic effects.

Fluoroquinolone antibiotics such as levofloxacin (Levaquin) and moxifloxacin (Avelox) inhibit topoisomerase IV and deoxyribonucleic acid (DNA) gyrase, which are essential enzymes that maintain the superhelical structure of DNA and are required for DNA replication and transcription, repair, recombination, and transposition.

Clindamycin (Cleocin), a lincosamide antibiotic, reversibly binds to 50S ribosomal subunits, preventing the formation of a peptide bond, which in turn inhibits bacterial protein synthesis.
Clindamycin is predominantly a bacteriostatic agent; however, depending upon drug concentration, infection site, and organism, it can also have bactericidal effects.

Cefpodoxime (Vantin) and cefixime (Suprax), third-generation cephalosporin antibiotics, inhibit synthesis of the bacterial cell wall by binding to one or more of the penicillin-binding proteins, causing the bacteria to lyse.

If symptoms decrease without onset of complications, therapy was successful.
If the common cold does not improve in 8 to 10 days, a bacterial cause is suspected, and antibiotic therapy is considered.

Drug information
Patient-oriented information sources
Lifestyle changes
Alternative therapies

Improving care of patients with lower respiratory tract infections-usually some form of pneumonia-has been the focus of multiple guidelines and organizations.
While upper respiratory infections are usually self-limiting and viral in nature, the pathogens responsible for causing pneumonia as well as the host response can be variable, leading to mixed outcomes.

Acute bronchitis is defined as a self-limiting inflammation of the bronchi (large airways) that leads to mild symptoms with or without cough.
Coughs may or may not be productive but may last up to six weeks.
Bronchitis may actually be a signal for other respiratory tract infections-such as flu, common cold, or pneumonia.
Because symptoms coincide with these other syndromes, it is often difficult to narrow the cause and correctly diagnose.
Most cases are viral.

The main goals of treatment are mostly targeted to symptom relief.
If treating for a specific bacterial or viral organism, treatment will also prevent transmission to others.

Both bacterial and viral pathogens can cause community-acquired pneumonia (CAP), either alone or in combination.
The most common bacterial pathogens are: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, Legionella species, and Chlamydia pneumoniae.

Diagnosis of CAP requires correlation with clinical symptoms with objective data, such as a chest x-ray.
Common clinical features include: cough with sputum production, fever, chest pain, and dyspnea.

The primary treatment goal is to decrease the duration of illness, prevent complications and progression of disease severity, and prevent transmission of disease.

Patients should have symptomatic improvement and achieve clinical stability within 48-72 hours of starting therapy.
If symptoms persist after 7 days or worsen, alternative antibiotic regimen can be trialed. However, repeated exposure to multiple antibiotics increases risk for developing bacterial resistance.

Amoxicillin 1 g TID
Augmentin 875/125 mg bid
Azithromycin 500mg day 1, then 250 mg days 2-5
Doxycycline 100 mg bid

URIs, including the common cold and rhinosinusitis, are some of the most common problems seen in primary care. URIs are usually self-limiting, minor illnesses that account for half or more of all acute illnesses.
URIs commonly involve rhinitis, which refers to irritation and inflammation of the intranasal mucous membrane and is characterized by nasal congestion, nasal discharge, sneezing, and postnasal drip.
URIs can progress to involve acute or chronic complications.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are the two most prevalent chronic respiratory diseases in the world (WHO, 2020). In comparison, asthma is more prevalent in children while COPD is more prevalent in adults.

Asthma has variable respiratory symptoms (e.g., intermittent cough, wheeze, dyspnea, etc.) with airflow limitation caused by an environmental exposure (e.g., allergic versus non-allergic) triggering an intermittent inflammatory response.
COPD has persistent respiratory symptoms (dyspnea, chronic cough, sputum, etc.) with airflow limitation caused by noxious particles or gases triggering a chronic inflammatory response.

Asthma's hallmark is the variable and intermittent nature of the symptoms (e.g., wheeze, dyspnea, chest tightness and cough) (GINA, 2020). Symptoms usually do not occur in isolation, vary over time and intensity, worsen overnight or upon waking, and can be triggered by exercise, allergens, extreme temperature, and viral infections.
COPD has a constellation of symptoms that hallmark the disease and include dyspnea, chronic cough or sputum production, and the presence of risk factor(s) (GOLD, 2020). A history of recurrent lower respiratory tract infections increases the index of suspicion for COPD.

Goals of drug therapy for asthma and COPD are similar and yet slightly different. The Global Initiative for Asthma (GINA) guideline goals of asthma management focus on good symptom control and the minimization of future asthma related morbidity and mortality, in collaboration with the patient's preferences.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline goals of COPD management are to reduce symptoms, to reduce exacerbation frequency and severity, and to improve exercise tolerance and overall health status.

Beta2-adrenergic agonists
Corticosteroids
Leukotriene modifiers
Mast cell stabilizers
Methylxanthines
Monoclonal antibodies

Ex. Albuterol (short acting SABA), Salmeterol (long acting LABA)
Beta2-adrenergic agonists stimulate beta2-adrenergic receptors, increasing the production of cyclic 3'5' adenosine monophosphate (cAMP).
Increased cAMP relaxes airway smooth muscle and increases bronchial ciliary activity.
Adverse effects of beta2-adrenergic receptor stimulation include increased skeletal muscle activity, central nervous system stimulation, hyperglycemia, and hypokalemia.

Ex. Ipratroprium (short acting SAMA, Aclidinium Bromide (long acting LAMA)
Muscarinic antagonists, previously referred to as anticholinergic drugs, competitively block acetylcholine at muscarinic receptors, decreasing cGMP.
The decreased cGMP results in a relatively higher proportion of cAMP. Increased cAMP relaxes airway smooth muscle and increases bronchial ciliary activity.

Ex. Montelukast
Two types of leukotriene modifiers: the 5-lipoxygenase (5-LO) inhibitors and the leukotriene receptor antagonists.
Zileuton inhibits 5-lipoxygenase (5-LO), preventing the first and second steps in the conversion of arachidonic acid to the bronchoconstrictor and proinflammatory cysteinyl leukotrienes (LTC4, LTD4, and LTE4).
Montelukast and zafirlukast bind to cysteinyl leukotriene receptors on eosinophils and other proinflammatory cells, preventing LTC4, LTD4, and LTE4 from binding to the receptors and the subsequent bronchoconstrictor and proinflammatory responses.

Ex. inhaled corticosteroids (Budesonide, Fluticasone, Mometasone Furoate) - low, medium or high dose, oral corticosteroids (more common with exacerbations)
Corticosteroids reduce airway inflammation by inhibiting or inducing the production of end-effector proteins.
End-effector proteins alter vascular tone, vascular permeability, and body water distribution; stimulate lipolysis, gluconeogenesis, and glycogen secretion; increase responsiveness of beta-adrenergic receptors; mobilize amino acids from muscles; impair leukocyte migration; and inhibit nuclear factor-kappa, which regulates production of proinflammatory proteins such as cytokines, interleukins, interferons, and chemokines.

Drug: Roflumilast inhibits phosphodiesterase 4, an enzyme commonly found in respiratory inflammatory cells (e.g., neutrophils, monocytes, macrophages, CD4+ and CD8+ T lymphocytes) and structural cells (e.g., endothelial cells, epithelial cells, smooth muscle cells, and fibroblasts).
Phosphodiesterase 4 inhibition increases intracellular cAMP, modifying the inflammatory response in these respiratory cells and structures.
Mainly used for reducing severe COPD flare-ups but NOT for acute relief.

Methylxanthine bronchodilators (ex. theophylline, aminophylline) relax bronchial smooth muscle, enhance diaphragmatic contractility, and have a slight antiinflammatory effect; the exact mechanisms of action are not known.
Theophylline and aminophylline, the ethylenediamine salt of theophylline, are dosed to a target plasma drug concentration. Therapeutic theophylline serum drug concentration range is generally accepted to be 10-20 mg/L.
Usually, second line because of narrow therapeutic index as maintenance treatment - serious adverse effects.

Mucolytics (acetylcysteine) break down the disulfide bonds and thereby decrease mucus viscosity, making it ideal for COPD sputum management.

All anti-IL-5/5R (inflammatory cytokines) agents are indicated for the maintenance therapy in persons with severe asthma with eosinophilic phenotype.
Dupilumab (>=12 years) is indicated for moderate to severe asthma with eosinophilic phenotype.
Omalizumab is indicated for therapy of persons >=6 years with moderate to severe allergic asthma with total serum immunoglobulin E levels from 30 to 700 IU/mL.

GINA and GOLD guidelines recommend that all persons with asthma or COPD receive an annual influenza vaccine.
Influenza vaccination can reduce exacerbation risk due to lower respiratory tract infection. The GINA guideline does not recommend pneumococcal vaccination in persons with asthma.

Mast cell stabilizers prevent the release and synthesis of proinflammatory mediators by inhibiting the influx of calcium into activated mast cells.
Cromolyn is marketed as a solution for nebulization (20 mg/2 mL). The initial dose is 20 mg four times daily. Once asthma symptoms are controlled, the dose may be tapered to the lowest effective dose (e.g., 20 mg three to four times daily).

A practitioner prescribes theophylline for a patient diagnosed with asthma. What classification of medication is theophylline?
A. Corticosteroid
B. Leukotriene modifier drug
C. Mast cell stabilizer
D. Methylxanthine

D. Methylxanthine
Rationale: Methylxanthine bronchodilators include theophylline and aminophylline. The therapeutic theophylline serum drug concentration range is generally accepted to be 10-20 mg/L; persons with asthma may do well with lower serum drug concentrations or experience unacceptable adverse effects with plasma drug concentrations within the therapeutic range.

A practitioner is treating a patient who has Step 2 mild persistent asthma. What is the recommended therapy?
A. Low-dose corticosteroid
B. Cromolyn, a leukotriene modifier, or theophylline
C. Combination of low-dose inhaled corticosteroid plus a leukotriene modifier or theophylline
D. Combination of medium-dose inhaled corticosteroid plus a leukotriene modifier or theophylline

A. Low-dose corticosteroid or
B. Cromolyn, a leukotriene modifier, or theophylline or
Rationale: Recommended therapy would be low dose corticosteroid. Alternative therapies to low-dose inhaled corticosteroids for persons with Step 2 mild persistent asthma include cromolyn, a leukotriene modifier, or theophylline. Alternative therapies to the combination of a low-dose inhaled corticosteroid and a long-acting beta2-adrenergic agonist bronchodilator for persons with Step 3 moderate persistent asthma include a combination of low-dose inhaled corticosteroid plus a leukotriene modifier or theophylline. For Step 4 moderate persistent asthma, combination of medium-dose inhaled corticosteroid plus a leukotriene modifier or theophylline is recommended.

Supplemental oxygen is not indicated in the routine management of asthma. However, the exchange of oxygen and carbon dioxide worsens as COPD progresses.
If peripheral oxygen saturation level via pulse oximetry is less than 92%, an arterial or capillary blood gas should be obtained.
Supplemental oxygen may have symptom benefit even if the patient is not hypoxemic. In COPD patients with severe resting chronic hypoxemia, long-term oxygen therapy (>15 hours per day) improves survival.

Antibiotics are not indicated in the routine management of asthma.
However, recent studies have demonstrated that regular use of azithromycin (250 mg per day or 500 mg three times per week) decreased exacerbation risk over 1 year.
Azithromycin used in such a manner can increase bacterial resistance, cause QTc interval prolongation, and impaired hearing.
Smoking negates any benefit with azithromycin.

Pediatric
Geriatric
Women
Ethnic
Genomics

Self-monitoring
Respiratory drug delivery systems
Drug information
Nutrition and lifestyle changes
Complementary and alternative drugs

Arcangelo, V. (2022). Pharmacotherapeutics for Advanced Practice: A Practical Approach. 5th ed.
Wolters Kluwer. Philadelphia, PA