Chapter 7 Respiratory System PDF

§ The respiratory system is composed of the upper respiratory tract, which includes the nose, pharynx, larynx, and trachea, and the lower respiratory tract, which includes the bronchial tree and the alveoli. § Inflammation of the upper respiratory tract is seen in many disorders, including the c...

§ The respiratory system is composed of the upper respiratory tract, which includes the nose, pharynx, larynx, and trachea, and the lower respiratory tract, which includes the bronchial tree and the alveoli. § Inflammation of the upper respiratory tract is seen in many disorders, including the common cold, seasonal rhinitis, sinusitis, pharyngitis, and laryngitis. § Inflammation of the lower respiratory tract can result in serious disorders that interfere with gas exchange, including bronchitis and pneumonia. § Obstructive disorders interfere with the ability to deliver gases to the alveoli because of obstructions in the conducting airways and eventually in the respiratory airways. These disorders include asthma and COPD. § Drugs that affect the respiratory system work to keep the airways open and gases moving efficiently. Cough Remedies § Antitussives are drugs that suppress the cough reflex, which act directly on the medullary cough center of the brain to depress the cough reflex. § Many disorders of the respiratory tract, including the common cold, sinusitis, pharyngitis, and pneumonia, are accompanied by an uncomfortable, unproductive cough. § Persistent coughing can be exhausting and can cause muscle strain and further irritation of the respiratory tract. § All of these drugs are indicated for the treatment of nonproductive cough. Pharmacokinetics § Codeine, hydrocodone, and dextromethorphan are rapidly absorbed, metabolized in the liver, and excreted in urine. § They cross the placenta and enter breast milk. § Benzonatate is metabolized in the liver and excreted in urine. Contraindications and Cautions § Antitussives are contraindicated in patients who need to cough to maintain the airways (e.g., postoperative patients and those who have undergone abdominal or thoracic surgery) to avoid respiratory distress. § Careful use is recommended for patients with asthma and emphysema because cough suppression in these patients could lead to an accumulation of secretions and a loss of respiratory reserve. § Caution should also be used in patients who are hypersensitive to or have a history of addiction to narcotics (codeine, hydrocodone). § These drugs should not be used during pregnancy and lactation. Adverse Effects § Traditional antitussives have a drying effect on the mucous membranes and can increase the viscosity of respiratory tract secretions. § Because they affect centers in the brain, these antitussives are associated with CNS adverse effects, including drowsiness and sedation. § Their drying effect can lead to nausea, constipation, and complaints of dry mouth. § The locally acting antitussives are associated with GI upset, headache, feelings of congestion, and sometimes dizziness. § Guaifenesin enhances the output of respiratory tract fluids by reducing the adhesiveness and surface tension of these fluids, allowing easier movement of the less viscous secretions. The result of this thinning of secretions is a more productive cough and thus decreased frequency of coughing. § Indicated for symptomatic relief of respiratory conditions characterized by a dry, nonproductive cough, including the common cold, acute bronchitis, and influenza Pharmacokinetics § Guaifenesin is rapidly absorbed, with an onset of 30 minutes and a duration of 4 to 6 hours. § Sites of metabolism and excretion have not been reported. Adverse Effects § The most common adverse effects associated with expectorant are GI symptoms (e.g., nausea, vomiting, anorexia). § Some patients experience headache, dizziness, or both; occasionally, a mild rash develops. § Mucolytics increase or liquefy respiratory secretions to aid the clearing of the airways in high-risk respiratory patients who are coughing up thick, tenacious secretions. § Acetylcysteine affects the mucoproteins in the respiratory secretions by splitting apart disulfide bonds that are responsible for holding the mucus material together. The result is a decrease in the tenacity and viscosity of the secretions. § Dornase alfa is a mucolytic prepared by recombinant DNA techniques that selectively break down respiratory tract mucus by separating extracellular DNA from proteins. It is used in cystic fibrosis, which is characterized by thick, tenacious mucous production. Pharmacokinetics § The medication may be administered by nebulization or by direct instillation into the trachea via an endotracheal tube or tracheostomy. § Acetylcysteine is metabolized in the liver and excreted somewhat in urine. Contraindications and Cautions § Caution should be used in cases of acute bronchospasm, peptic ulcer, and esophageal varices because the increased secretions could aggravate the problem. § Adverse Effects § Adverse effects most commonly associated with mucolytic drugs include GI upset, stomatitis, rhinorrhea, bronchospasm, and occasionally a rash.  Drugs used in Bronchial Asthma § They are medications used to facilitate respirations by dilating the airways. They are helpful in symptomatic relief or prevention of bronchial asthma and for bronchospasm associated with COPD. § Several of the bronchodilators are administered orally and absorbed systemically, giving them the potential for many systemic adverse effects. § Other medications are administered directly into the airways by nebulizers. These medications have the advantage of fewer systemic adverse reactions. § Bronchodilators include xanthines, sympathomimetics, and anticholinergics. § These drugs were once the main treatment choices for asthma and bronchospasm. However, because they have a relatively narrow margin of safety and interact with many other drugs, they are no longer considered the first-choice bronchodilators. § They have a direct effect on the smooth muscles of the respiratory tract, both in the bronchi and in the blood vessels. § Xanthines also inhibit the release of slow reacting substance of anaphylaxis (SRSA) and histamine, decreasing the bronchial swelling and narrowing that occurs as a result of these two chemicals. § Xanthines used to treat respiratory disease include aminophylline, caffeine, dyphylline, and theophylline. Pharmacokinetics § The xanthines are rapidly absorbed from the GI tract when given orally. § They are also given IV, reaching peak effects within minutes. § They are widely distributed and metabolized in the liver and excreted in urine. § Xanthines cross the placenta and enter breast milk. Contraindications and Cautions § Caution should be taken with any patient with GI problems, coronary disease, respiratory dysfunction, renal or hepatic disease, alcoholism, or hyperthyroidism because these conditions can be exacerbated by the systemic effects of xanthines. Adverse Effects § Adverse effects associated with xanthines are related to theophylline levels in the blood. § Therapeutic theophylline levels are from 10 to 20 mcg/mL. § With increasing levels, predictable adverse effects are seen, ranging from GI upset, nausea, irritability, and tachycardia to seizures, brain damage, and even death. § Nicotine increases the metabolism of xanthines in the liver; xanthine dose must be increased in patients who continue to smoke while using xanthines. § In addition, extreme caution must be used if the patient decides to decrease or discontinue smoking, because severe xanthine toxicity can occur. § One of the actions of the sympathetic nervous system is dilation of the bronchi with increased rate and depth of respiration. This is the desired effect when selecting a sympathomimetic as a bronchodilator. § Most of the sympathomimetics used as bronchodilators are beta2-selective adrenergic agonists. That means that at therapeutic levels their actions are specific to the beta2- receptors found in the bronchi. This specificity is lost at higher levels. § Other systemic effects of sympathomimetics include increased blood pressure, increased heart rate, vasoconstriction, and decreased renal and GI blood flow—all actions of the sympathetic nervous system. These overall effects limit the systemic usefulness of these drugs in certain patients. § Epinephrine, the prototype drug, is the drug of choice in adults and children for the treatment of acute bronchospasm, including that caused by anaphylaxis; it is also available for inhalation. Pharmacokinetics § Sympathomimetics available only as an inhalant include the arformoterol, formoterol, indacaterol, isoetharine, levalbuterol, pirbuterol, and salmeterol. They vary in their duration of action. § Other sympathomimetics are available in various forms. Albuterol and metaproterenol are available in inhaled and oral forms. Terbutaline can be used as an inhalant and as an oral and parenteral agent. Isoproterenol is available for intravenous use. Ephedrine is used orally and in parenteral form. § These drugs are rapidly distributed after injection; they are transformed in the liver to metabolites that are excreted in the urine. Contraindications and Cautions § These drugs are contraindicated or should be used with caution, depending on the severity of the underlying condition, including cardiac disease, vascular disease, arrhythmias, diabetes, and hyperthyroidism. Adverse Effects § Adverse effects of these drugs, which can be attributed to sympathomimetic stimulation, include central nervous system stimulation, GI upset, cardiac arrhythmias, hypertension, bronchospasm, sweating, pallor, and flushing. § Isoproterenol is associated with more cardiac side effects than some other drugs. § Patients who cannot tolerate the sympathetic effects of the sympathomimetics might respond to the anticholinergic drugs ipratropium and tiotropium. § Anticholinergics are used as bronchodilators because of their effect on the vagus nerve, which is to block or antagonize the action of the neurotransmitter acetylcholine at vagal-mediated receptor sites. § Normally, vagal stimulation results in a stimulating effect on smooth muscle, causing contraction. Pharmacokinetics § These drugs are available for inhalation, using an inhaler device. Ipratropium is also available as a nasal spray for seasonal rhinitis. § Ipratropium has an onset of action of 15 minutes when inhaled. It is generally not absorbed systemically. § Tiotropium has a rapid onset of action and a long duration. It is excreted unchanged in urine. Contraindications and Cautions § Caution should be used in any condition that would be aggravated by these drugs such as narrow-angle glaucoma, bladder neck obstruction or prostatic hypertrophy, and conditions aggravated by dry mouth and throat. § The use of ipratropium or tiotropium is contraindicated in the presence of known allergy to the drug or to soy products or peanuts (the vehicle used to make ipratropium an aerosol contains a protein associated with peanut allergies). § These drugs are not usually absorbed systemically, but as with all drugs, caution should be used in pregnancy and lactation. Adverse Effects § Adverse effects are related to the anticholinergic effects of the drug if it is absorbed systemically. These effects include dizziness, headache, fatigue, nervousness, dry mouth, sore throat, palpitations, and urinary retention. § The second component of treating obstructive pulmonary disorders that is to alter the inflammatory process that leads to swelling and further airway narrowing. § The drugs used to affect inflammation are the inhaled steroids, the leukotriene receptors, and a mast cell stabilizer, which can affect both bronchodilation and inflammation § Inhaled steroids have been found to be a very effective treatment for bronchospasm. § In an airway that is swollen and narrowed by inflammation and swelling, steroid action will increase air flow and facilitate respiration. § Inhaling the steroid tends to decrease the numerous systemic effects that are associated with steroid use. § When administered into the lungs by inhalation, steroids decrease the effectiveness of the inflammatory cells. Pharmacokinetics § These drugs are rapidly absorbed from the respiratory tract, but they take from 2 to 3 weeks to reach effective levels, and so patients must be encouraged to take them to reach and then maintain the effective levels. § They are metabolized by natural systems, mostly within the liver, and are excreted in urine. § The glucocorticoids are known to cross the placenta and to enter breast milk. Contraindications and Cautions § Inhaled steroids are not for emergency use and not for use during an acute asthma attack or status asthmaticus. § They should not be used during pregnancy or lactation unless benefit outweigh the risk. § These preparations should be used with caution in any patient who has an active infection of the respiratory system because the depression of the inflammatory response could result in serious illness. Adverse Effects § Adverse effects are limited because of the route of administration. § Sore throat, hoarseness, coughing, dry mouth, and pharyngeal and laryngeal fungal infections are the most common side effects encountered. § Leukotriene receptor antagonists selectively and competitively block (zafirlukast, montelukast) or antagonize (zileuton) receptors for the production of leukotrienes D4 and E4, components of SRSA. § As a result, these drugs block many of the signs and symptoms of asthma, such as neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. § These factors contribute to the inflammation, edema, mucus secretion, and bronchoconstriction seen in patients with asthma. § They do not have immediate effects on the airways and are not indicated for treating acute asthma attacks. Pharmacokinetics § These drugs are given orally. They are rapidly absorbed from the GI tract. § Zafirlukast and montelukast are extensively metabolized in the liver by the cytochrome P450 system and are primarily excreted in feces. § Zileuton is metabolized and cleared through the liver. § These drugs cross the placenta and enter breast milk. Contraindications and Cautions § These drugs should be used cautiously in patients with hepatic or renal impairment § These drugs should be used during pregnancy only if the benefit to the mother clearly outweighs the potential risks to the fetus. Adverse Effects § Adverse effects associated with leukotriene receptor antagonists include headache, dizziness, nausea, diarrhea, abdominal pain, elevated liver enzyme concentrations, vomiting, generalized pain, fever, and myalgia. § A mast cell stabilizer prevents the release of inflammatory and broncho- constricting substances when the mast cells are stimulated to release these substances because of irritation or the presence of an antigen. § Cromolyn is the only drug still available in this class, only available in an over-the- counter form, and it is no longer considered part of the treatment standards because of the availability of more specific and safer drugs like first generation antihistamine like chloropheneramine and second-generation antihistamine like desloratidtine and loratadine that are histamine receptor blockers