Drugs Acting on the Lower Respiratory Tract PDF

Chapter 55 Drugs Acting on the Lower Respiratory Tract Copyright Copyright © 2012 © 2017 Wolters Wolters Kluwer Kluwer...

Chapter 55 Drugs Acting on the Lower Respiratory Tract Copyright Copyright © 2012 © 2017 Wolters Wolters Kluwer Kluwer Health All | Lippincott Rights Reserved Williams & Wilkins Pulmonary Obstructive Diseases #1  Asthma o Associated with development of IgE antibodies to specific antigens that, when activated, cause the immediate release of inflammatory chemicals from mast cells  Causes rapid swelling of the inner lining of the airways and a narrowing of the conducting tubes  COPD o Most often caused by chronic exposure to irritants that cause a chronic inflammation and swelling in the airway o Muscular and cilial action is lost; complications related to the loss of these protective processes can occur Copyright © 2023 Wolters Kluwer All Rights Reserved Pulmonary Obstructive Diseases #2 Respiratory distress syndrome o Causes obstruction at the alveolar level o Seen in neonates o Obstruction related to lack of the lipoprotein surfactant Adult respiratory distress syndrome o Characterized by progressive loss of lung compliance and increasing hypoxia o Occurs as a result of a severe insult to the body Copyright © 2023 Wolters Kluwer All Rights Reserved Use of Lower Respiratory Tract Agents Across the Lifespan Copyright © 2023 Wolters Kluwer All Rights Reserved Bronchodilators Used to facilitate respiration by dilating the airways Helpful in symptomatic relief or prevention of bronchial asthma and for bronchospasm associated with COPD Xanthines Sympathomimetics Anticholinergics Copyright © 2023 Wolters Kluwer All Rights Reserved Xanthines #1 Come from a variety of natural sources Were once main treatments for asthma and bronchospasm Relatively narrow margin of safety; no longer first choice Drugs o Caffeine (Cafcit, Caffedrine, others) o Aminophylline (generic) o Theophylline (Elixophyllin, Theo-24, Theochron) Copyright © 2023 Wolters Kluwer All Rights Reserved Xanthines #2  Therapeutic actions o Direct effect on the smooth muscles of the respiratory tract, both in the bronchi and in the blood vessels o Exact mechanisms not known with certainty o May affect mobilization of calcium  Indications o Treatment of COPD and bronchospasm; asthma  Pharmacokinetics o Rapidly absorbed from GI tract o Metabolized in the liver; excreted in the urine o Cross placenta and enter human milk Copyright © 2023 Wolters Kluwer All Rights Reserved Xanthines #3  Contraindications o GI problems, coronary disease, respiratory dysfunction, renal or hepatic disease, alcoholism, or hyperthyroidism  Cautions o Pregnancy and lactation  Adverse effects o Theophylline: related to levels in the blood  Risk increases with levels higher than 20 mcg/mL  Drug–drug interactions o Many drugs interact with xanthines o Substances in cigarettes Copyright © 2023 Wolters Kluwer All Rights Reserved Xanthine Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Sympathomimetics #1  Mimic effects of the o Formoterol (Foradil and sympathetic nervous system others)  Dilate bronchi; increase rate o Isoproterenol (Isuprel and depth of respiration and others) o Albuterol (Proventil HFA o Levalbuterol (Xopenex and others) HFA) o Arformoterol (Brovana) o Metaproterenol (generic) o Ephedrine (generic) o Olodaterol (Striverdi) o Epinephrine (EpiPen and o Salmeterol (Serevent) others) o Terbutaline (generic) Copyright © 2023 Wolters Kluwer All Rights Reserved Sympathomimetics #2  Therapeutic actions o Most are beta2-selective adrenergic agonists  Indications o Some: short-term/emergency use to reverse bronchospasm in allergic reaction or asthma attack o Others: longer acting, taken on scheduled basis to decrease symptoms of COPD or asthma  Pharmacokinetics o Rapidly distributed o Transformed in the liver to metabolites that are excreted in the urine Copyright © 2023 Wolters Kluwer All Rights Reserved Sympathomimetics #3  Contraindications and cautions o Underlying conditions that would be aggravated by sympathetic stimulation: contraindication or caution depends on severity o Pregnancy and lactation  Adverse effects o Attributed to sympathomimetic stimulation o Rare: life-threatening paradoxical bronchospasm  Drug–drug interactions o General anesthetics cyclopropane and halogenated hydrocarbons o Other medications that increase heart rate, blood pressure Copyright © 2023 Wolters Kluwer All Rights Reserved Sympathomimetic Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #1 Please answer the following question as true or false. The adverse effects of theophylline are related to levels in the blood and include seizures and life- threatening arrhythmias. Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #1 True Rationale: Adverse effects associated with theophylline are related to levels in the blood. There are increased chances of side effects including nausea, vomiting, irritability, tremors, nervousness, insomnia, and tachyarrhythmias when levels are higher than 20 mcg/mL. Symptoms of severe toxicity include seizures, life-threatening arrhythmias, hypotension, and coma. Copyright © 2023 Wolters Kluwer All Rights Reserved Anticholinergics #1  Not as fast acting as sympathomimetics  Can provide maintenance treatment with fewer side effects  Drugs o Ipratropium (Atrovent) o Tiotropium (Spiriva) o Aclidinium (Tudorza Pressair) o Glycopyrrolate (Lonhala Magnair) o Revefenacin (Yupelri) o Umeclidinium (Incruse Ellipta) Copyright © 2023 Wolters Kluwer All Rights Reserved Anticholinergics #2  Therapeutic actions o Block or antagonize action of acetylcholine at vagal- mediated receptor sites  Relaxation of smooth muscle in bronchi  Indications o Treatment of bronchospasm in patients with COPD  Pharmacokinetics o When inhaled, most is not absorbed o Metabolism, excretion, and half-lives vary o Most are partially excreted unchanged in urine Copyright © 2023 Wolters Kluwer All Rights Reserved Anticholinergics #3  Contraindications o Known allergy  Cautions o Any condition that would be aggravated by the anticholinergic or atropinelike effects of the drug o Pregnancy and lactation  Adverse effects o Local effects o Anticholinergic effects if absorbed systematically  Drug–drug interactions o Other anticholinergics Copyright © 2023 Wolters Kluwer All Rights Reserved Anticholinergic Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Drugs Affecting Inflammation Alter inflammatory process that leads to swelling, excessive mucous, and more airway narrowing Inhaled steroids Mast cell stabilizer Copyright © 2023 Wolters Kluwer All Rights Reserved Inhaled Steroids #1 Effective treatment for prevention and treatment of inflammation Drug of choice depends on patient response Drugs o Beclomethasone (QVAR Redihaler) o Budesonide (Pulmicort Respules, Pulmicort Flexhaler) o Ciclesonide (Alvesco) o Fluticasone (Flovent Diskus, Flovent HFA) o Triamcinolone (generic) Copyright © 2023 Wolters Kluwer All Rights Reserved Inhaled Steroids #2  Therapeutic actions o Decrease effectiveness of inflammatory cells  Decreases swelling  Promotes beta-adrenergic receptor activity o Indications o Prevention and treatment of asthma o Other indications vary by drug  Pharmacokinetics o Rapidly absorbed from the respiratory tract o Metabolized mostly within the liver; excreted in the urine o Glucocorticoids cross placenta and enter human milk Copyright © 2023 Wolters Kluwer All Rights Reserved Inhaled Steroids #3  Contraindications o Not for emergency use o Pregnancy or lactation  Cautions o Active infection of respiratory system  Adverse effects o Usually fewer adverse effects when inhaled o Sore throat, hoarseness, coughing, dry mouth o Pharyngeal and laryngeal fungal infections o Long-term use: glaucoma, cataracts, decreased bone mineral density  Drug–drug interactions o None known Copyright © 2023 Wolters Kluwer All Rights Reserved Inhaled Steroid Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Leukotriene Receptor Antagonists #1 Developed to act more specifically at the site of the problem associated with asthma Drugs o Zafirlukast (Accolate) o Montelukast (Singulair) o Zileuton (Zyflo) Copyright © 2023 Wolters Kluwer All Rights Reserved Leukotriene Receptor Antagonists #2  Therapeutic actions o Selectively and competitively block or antagonize receptors for the production of leukotrienes  Indications o Prophylaxis and treatment of asthma  Pharmacokinetics o Rapidly absorbed from GI tract o Metabolized in the liver; excretion varies o Cross placenta and enter human milk Copyright © 2023 Wolters Kluwer All Rights Reserved Leukotriene Receptor Antagonists #3 Contraindications o Not indicated for treatment of acute asthma attacks Cautions o Zeleuton and zafirlukast: hepatic or renal impairment o Pregnancy and lactation Copyright © 2023 Wolters Kluwer All Rights Reserved Leukotriene Receptor Antagonists #4  Adverse effects o Upper respiratory infection, pharyngitis, cough, headache, dizziness, nausea, diarrhea, abdominal pain, elevated liver enzyme concentrations, vomiting, generalized pain, fever, myalgia. o Serious neuropsychiatric events have been reported.  Drug–drug interactions o Warfarin, theophylline, phenytoin, aspirin, others. o Check for interactions before administering the drug. Copyright © 2023 Wolters Kluwer All Rights Reserved Leukotriene Receptor Antagonist Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Immune Modulators #1 Indicated for add-on maintenance therapy for patients with moderate to severe asthma Drugs o Benralizumab (Fasenra) o Dupilumab (Dupixent) o Mepolizumab (Nucala) o Omalizumab (Xolair) o Reslizumab (Cinqair) Copyright © 2023 Wolters Kluwer All Rights Reserved Immune Modulators #2 Therapeutic actions o Bind to specific receptors to decrease inflammation Indications o Add-on maintenance therapy for asthma Pharmacokinetics o Most are administered subcutaneously and are absorbed slowly over several days o Most have pregnancy registries to gather information on outcomes Copyright © 2023 Wolters Kluwer All Rights Reserved Immune Modulators #3 Contraindications o Not indicated for treatment of acute asthmatic attacks o Hypersensitivity reactions to components Adverse effects o Variety of effects; vary by specific drug Drug–drug interactions o Corticosteroids Copyright © 2023 Wolters Kluwer All Rights Reserved Immune Modulator Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Mast Cell Stabilizer Prevents release of inflammatory and bronchoconstricting substances Cromolyn (generic) only drug available No longer part of treatment standards; more specific and safer drugs are available Copyright © 2023 Wolters Kluwer All Rights Reserved Lung Surfactants #1 Naturally occurring compounds or lipoproteins Contain lipids and apoproteins that reduce surface tension within the alveoli o Allows expansion for gas exchange Drugs o Beractant (Survanta) o Calfactant (Infasurf) o Poractant (Curosurf) Copyright © 2023 Wolters Kluwer All Rights Reserved Lung Surfactants #2  Therapeutic actions o Replace the surfactant missing in the lungs of neonates with RDS  Indications o Rescue treatment of infants who have RDS  Pharmacokinetics o Begin to act immediately on instillation into the trachea o Metabolized in the lungs by normal surfactant metabolic pathways  Contraindications o Emergency drug; no contraindications Copyright © 2023 Wolters Kluwer All Rights Reserved Lung Surfactants #3  Adverse effects o Patent ductus arteriosus o Bradycardia o Hypotension o Intraventricular hemorrhage o Pneumothorax o Pulmonary air leak o Hyperbilrubinemia o Sepsis  Drug–drug interactions not expected because of instillation into trachea Copyright © 2023 Wolters Kluwer All Rights Reserved Lung Surfactant Prototype Copyright © 2023 Wolters Kluwer All Rights Reserved Question #2 Which of the following is a contraindication to using lung surfactants? A. Prematurity B. Renal insufficiency C. No contraindications D. COPD Copyright © 2023 Wolters Kluwer All Rights Reserved Answer to Question #2 C. No contraindications Rationale: Because lung surfactants are used as emergency drugs in the newborn, there are no contraindications. Copyright © 2023 Wolters Kluwer All Rights Reserved Other Drugs Used to Treat Lower Respiratory Tract Disorders Other major pathophysiology that can affect lower respiratory tract is infection Drugs to treat: o Bacterial infection: Chapter 9 o Viral infection: Chapter 10 o Fungal infection: Chapter 11 o Protozoal infection: Chapter 12 Copyright © 2023 Wolters Kluwer All Rights Reserved