Pharmacology of Drugs Used to Treat Asthma by Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Integrated Scientific and Clinical Pharmacology

Pharmacology of Drugs Used to Treat Asthma Marc Imhotep Cray, M.D. BMS / CK-CS Teacher

http://www.imhotepvirtualmedsch.com/

Principles of Drug Therapy

OBJECTIVES 1. Understand the medications used in the treatment of asthma, their mechanisms of action, and adverse effects. 2. Know the difference between short-acting symptomatic treatments and long acting preventive therapies.

3. List the mediators of airway inflammation involved in asthma. Companion learning strings: o MedPharm Guidebook UNIT 7: Drugs used in disorders of the respiratory system. eNotes: o Respiratory Pharmacology o Autocoids, Ergots, Anti-inflammatory Agents, and Immunosuppressive Agents Marc Imhotep Cray, M.D.

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Clinical Case An 8-year-old boy is brought to your office because of a chronic cough. His mother says that he coughs frequently throughout the day and will have symptoms 2 or 3 nights a month as well. This has been a problem on and off for approximately a year, but seems to be worse in the spring and fall. He also coughs more when he is riding his bike or playing soccer. He has been treated twice in the past year for “bronchitis” with antibiotics and cough suppressants but he never seems to clear up completely. His examination is normal except for his lungs, which reveal expiratory wheezing. You diagnose him with asthma and prescribe an albuterol inhaler.  What is the mechanism of action of albuterol?  What are the most common side effects of albuterol?  What medications can be used to provide long-term control of the asthma  symptoms? Marc Imhotep Cray, M.D.

Principles of Drug Therapy

What is Asthma and How is it Treated?  Asthma, involves constriction of pulmonary passages and secretion of  excess mucus, and is characterized by  dyspnea  Coughing  wheezing  chest tightness  Can be precipitated by triggers such as  allergens  cold air  viral infections  bacterial infections Marc Cray, M.D.  Imhotep exercise

Major drug classes used for asthma:  anti-IgE antibodies  mast cell degranulation blockers  smooth muscle relaxants  anti-inflammatory agents

Principles of Drug Therapy

What is Asthma (2) ď&#x201A;§ Asthma is a disease process characterized by episodic reversible bronchoconstriction of hyperreactive airways in response to various exogenous and endogenous stimuli ď&#x201A;§ Asthma is also associated with chronic inflammation

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Types of Asthma  Older classification: Extrinsic and intrinsic  Newer preferred classification  Atopic: A type I hypersensitivity reaction with strong familial tendencies  Nonatopic: Asthma associated with viral infection (e.g. rhinovirus, parainfluenza virus) in patients with no family history of allergies and who have normal levels of IgE  Drug-induced asthma  Occupational asthma  Cardiac asthma Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Types of Asthma (2) Alternative classification: Allergic asthma versus nonallergic asthma  Allergic asthma    

Epidemiology: Occurs more frequently in children Associated conditions: Patients may have hay fever or eczema Mechanism of allergic asthma: Type I hypersensitivity reaction Causes: Pollens, dust, drugs

 Nonallergic asthma  Epidemiology: Occurs more frequently in adults  Mechanism of nonallergic asthma: Not type I hypersensitivity reaction; IgE levels are normal  Causes: Exercise, cold air, drugs, gastroesophageal reflux, viral infections Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Clinical presentation of asthma Symptoms:  Classic triad is persistent wheezing, chronic episodic dyspnea, and chronic nonproductive cough  Symptoms may be worse, or only present at night, due to the physiologic drop in cortisol secretion  Night-time cough, which may be the only symptom, is a classic symptom of asthma.  Dark rings under the eyes (“allergic shiners”) and a dark transverse crease on the nose (“allergic salute”) are often seen, especially in children

 Status asthmaticus is a prolonged asthmatic attack, which can be fatal Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Clinical presentation of asthma (2) Laboratory studies:  Low peak expiratory flow (PEF)  FEV1/FVC is often decreased as in other obstructive lung diseases, and residual volume is increased  Carbon dioxide is usually low in an acute asthma exacerbation secondary to hyperventilation  a rising carbon dioxide concentration in this setting often precedes respiratory failure

 Eosinophilia may be present Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Pathogenesis of Asthma Extrinsic and Intrinsic Asthma (See NIP 7-7) Pharmacotherapy of asthma depends on understanding the disease pathogenesis ď&#x201A;§ In the immunologic, or antigen challenge model, IgE antibodies produced by airway mucosa mast cells mediate asthma

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Pathogenesis of Asthma (2) ď&#x201A;§ B lymphocytes synthesize IgE antibodies after exposure to an antigen>>> IgE antibodies attach to mast cells and, with re-exposure to antigen, form antigen-antibody complexes ď&#x201A;§ complexes trigger synthesis and release of mediators, such as histamine, leukotrienes (LTC4 and LTD4), and prostaglandins, from mast cells>>> bronchoconstriction and vascular leakage result Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Asthma Pharmacotherapy  When exposure to allergens cannot be avoided, drug therapy is needed  Major goals is to reverse asthmatic symptoms and prevent recurrent episodes by disrupting actions of endogenous agents that worsen bronchospasm and inflammation

 Major classes of drugs* for asthma are (1) anti-IgE antibodies (2) blockers of mast cell degranulation (3) smooth muscle relaxants (4) antiinflammatory agents * Six classes of drugs used to treat asthma: 1) β-adrenoreceptor agonists 2) acetylcholine antagonists 3) glucocorticoids 4) leukotriene modifiers 5) chromones and 6) anti-IgE monoclonal antibodies Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Asthma Pharmacotherapy (2)  Bronchodilators were first and most effective treatment, but  a better approach is prophylactic use of antiinflammatory agents to control bronchial inflammation  With these agents, patients with asthma are rarely hospitalized, seriously ill, or in need of emergency treatment

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Asthma Pharmacotherapy (3)  With prophylactic use of antiinflammatory agents pts can control their disease, and therapy is much less expensive than previous emergency management  Now, antiinflammatory agents are the first-line therapy for patients who have more than occasional symptoms  Bronchodilators are still used but only when antiinflammatory therapy is inadequate, and then in smaller amounts Marc Imhotep Cray, M.D.

Principles of Drug Therapy

(1) Anti-lgE Antibodies  One of the more novel therapies is use of anti-IgE antibodies  In theory, drugs acting as anti-IgE antibodies would prevent IgE binding to mast cell surfaces

 This action reduces formation of activated antigen-IgE complexes and suppress release of mediators that induce immediate bronchoconstriction in the early phase  Mediators such as histamine, prostaglandins, and leukotrienes are unable to cause sneezing, wheezing, itching, and coughing

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Anti-lgE Antibodies (2) 

The most notable anti-IgE antibody, Rhumab-E25 (Omalizumab), is a recombinant humanized monoclonal antibody to IgE  By binding to circulating IgE in the blood, Rhumab-E25 blocks release of inflammatory mediators by keeping IgE from binding to mast cells 

This antibody, administered by parenteral injection, is currently in phase III clinical trials for seasonal allergic rhinitis and allergic asthma

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Immunologic basis of anti-IgE antibodies MOA

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-9

Principles of Drug Therapy

Rhumab-E25 Omalizumab ď&#x201A;§ Omalizumab blocks release of inflammatory mediators by keeping IgE from binding to mast cells

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

(2) Mast Cell Degranulation Blockers (Chromones)

 Cromolyn block mast cell degranulation by suppressing release of mediators of immediate bronchoconstriction (early response) and reduce eosinophil recruitment that causes airway inflammation  Does not directly alters smooth muscle tone or reverses bronchospasm

 Both banded in U.S.  inhaled as aerosols, can be used for intrinsic (antigen-induced) or extrinsic (non–antigen-induced) asthma Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Mast Cell Degranulation Blockers (2)  Poorly absorbed, so adverse effects are restricted to deposition site  Cromolyn (nasal spray) is preferred for young patients  Cromolyn alter Cl− channel function, which 1) on airway neurons underlies cough inhibition, 2) on mast cells delays antigen-evoked bronchoconstriction, and 3) on eosinophils prevents inflammatory responses to antigens

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Mast Cell Degranulation Blockers MOA Illustrated

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-10

Principles of Drug Therapy

(3) Bronchodilators (smooth muscle relaxants)

 Drugs that expand pulmonary airways (bronchi)-bronchodilators-block the early response by inhibiting immediate bronchoconstriction  smooth muscle relaxation  Some agents, especially theophylline and β2-adrenergic agonists, inhibit late response inflammation

 Used when a persistent cough and bronchial constriction are present  In addition to relaxing smooth muscles and reducing airway reactivity, bronchodilators reduce coughing, wheezing, and shortness of breath  Agents are usually given via inhalation, but some can be given orally or parenterally Marc Imhotep Cray, M.D. (intravenous, intramuscular, or subcutaneous route)

Principles of Drug Therapy

Bronchodilators (2)  Most drugs have a rapid onset of action (within minutes), but the effect usually wanes in 5 to 7 hours  Some agents, especially theophylline, inhibit the delayed response to antigen  Most common bronchodilators are 1) methylxanthines (eg, theophylline, caffeine) 2) β-adrenergic agonists (eg, isoproterenol, albuterol, epinephrine) 3) cholinergic antagonists (eg, atropine, tiotropium) Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-11

Principles of Drug Therapy

Methylxanthines ď&#x201A;§ methylxanthines theophylline, caffeine, and theobromine, found in cola, tea, and coffee ď&#x201A;§ are bronchodilators that reduce bronchial smooth muscle activity by causing increase intracellular cAMP levels

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Methylxanthines (2) Mechanism of Action MOA:  Signal molecules (eg, transmitters, drugs) activate GPCRs on airway smooth muscle cells and increase the conversion rate of ATP to cAMP >>> increased cAMP levels>>> relax bronchial muscle and reduce airway reactivity  Phosphodiesterase stops cAMP effects and reduces cAMP levels by catalyzing hydrolysis of cAMP to AMP  Methylxanthines prevent cAMP hydrolysis  Or, theophylline may block cell surface receptor effects of adenosine, which may induce bronchoconstriction and inflammation Marc Imhotep Cray, M.D. 26

Principles of Drug Therapy

Methylxanthines (3)  These drugs may also be antiinflammatory  Theophylline, most widely prescribed and of low cost, comes as:  short-acting tablets and syrups,  sustained-release capsules and tablets, and  intravenous doses  The synthetic dyphylline may help patients who are unable to use theophylline Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 12

Methylxanthines

Principles of Drug Therapy

Methylxanthine: Adverse Effects Methylxanthine doses must be closely watched  Low doses have little effect, if any, whereas high doses can affect central nervous, cardiovascular, skeletal muscle, GI, and renal systems  Theophylline is most selective at sm. mm.; caffeine induces most marked CNS effects  Even at low to moderate doses, they enhance cortical arousal & alertness & defer fatigue  In hypersensitive patients, insomnia and nervousness may occur Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Methylxanthine: Adverse Effects (2)  Methylxanthines reduce blood viscosity, increase blood flow, increase cardiac output, & induce tachycardia in healthy subjects  In sensitive persons, cardiac arrhythmias are common  These drugs strengthen contractions of isolated skeletal muscles in vitro and improve contractility & reverse fatigue of diaphragm in pts with COPD>>accounts for their usefulness in COPD  Although methylxanthines enhance gastric acid and digestive enzyme secretion in GI tract and induce a slight diuresis, these effects are minor Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 13

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

β-Adrenergic Agonists  β-adrenergic agonists enhance sympathetic discharge  Used to relieve a sudden asthma attack or block exercise-induced asthma EFFECTS:  Relax bronchial smooth muscle, inhibit mediator release, increase transport of mucus, and alter composition of mucus by stimulating β adrenoceptors

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

β-Adrenergic Agonists (2)  Bronchodilation is mediated by β2 adrenoceptors located on smooth muscle cells in airways  Nonselective β-adrenoceptor agonists (eg, epinephrine, ephedrine, isoproterenol) stimulate all β adrenoceptors (β1 and β2 classes)  These nonselective actions often produce adverse effects, particularly in CNS and cardiovascular system

 Selective drugs that activate only β2 receptors (eg, albuterol, terbutaline, salmeterol) are most commonly prescribed sympathomimetic agents Marc Imhotep Cray, M.D.

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Î˛-Adrenergic Agonists MOA Illustrated

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-14

Principles of Drug Therapy

Nonselective β-Adrenergic Agonists  Agents that activate both β1 and β2 adrenoceptors have long been used to treat asthma  These drugs are potent, rapidly acting bronchodilators, but their stimulation of the cardiac system is a serious drawback

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Nonselective β-Adrenergic Agonists (2) Major agents are epinephrine, ephedrine, and isoproterenol:  Epinephrine is either inhaled or given SQ and is the active agent in many OTC preparations  Maximal bronchodilation is achieved 15 minutes after injection and lasts approximately 90 minutes  B/c this drug stimulates cardiac output, increases heart rate, and exacerbates angina, physicians rarely prescribe it

 Ephedrine, used in China more than 2000 years ago, has longest history of use of any antiasthmatic  longer duration of action, lower potency, and greater oral activity than epinephrine  marked adverse effects, particularly in the CNS, and is rarely administered

 Isoproterenol has rapid onset of action, with peak bronchodilation occurring within 15 minutes of injection Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Selective β-Adrenergic Agonists  Selective β2-adrenoceptor activators are most widely prescribed sympathomimetic drugs  because of their β2 selectivity, oral activity, and rapid onset and long duration of action (4 hours)

 Major drugs- metaproterenol, terbutaline, albuterol, salmeterol, and formoterol -have minimal β1-mediated effects on nervous and cardiac systems  Inhalation route allows greatest local effects with fewest adverse effects  Inhaled agents cause bronchodilation equal to isoproterenol and persists for 4 hours Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Selective β-Adrenergic Agonists (2)  Terbutaline, metaproterenol, and albuterol can be given orally as tablets  Terbutaline, the only drug that can be used subcutaneously, is given for severe asthma attacks or if insensitivity to inhaled agents exists  Two new drugs, salmeterol and formoterol, have a long duration of action and high lipid solubility  Both drugs at high concentrations move slowly into airway smooth muscle, so effects can last up to 12 hours  Both also enhance antiasthmatic actions of corticosteroids Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Catecholamine Action on Îą and Î˛ Receptors of Heart and Bronchial Tree Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-14

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Antimuscarinic Agents (Muscarinic Antagonists)  Acetylcholine mediates its physiologic effects via 2 types of receptors:  muscarinic and nicotinic  Muscarinic receptors are GPCRs that are densely expressed in the airways  When stimulated, muscarinic receptors cause muscle contraction>>> leads to narrowing of airways and bronchoconstriction

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Antimuscarinic Agents (2)  Muscarinic antagonists, or anticholinergics, prevent acetylcholine from producing smooth muscle contractions & excess mucus in bronchi  Ipratropium bromide and atropine are most commonly used  Anticholinergics are less effective than β2-adrenergic activators  However, these drugs enhance bronchodilation induced by β2-adrenoceptor agonists, so patients often take both anticholinergics and β2 agonists  Major adverse effects = dry mouth, bitter taste, scratchy throat, and headache Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Antimuscarinic Agents MOA Illustrated

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-17

Principles of Drug Therapy

(4) Anti-inflammatory Agents: Corticosteroids  Corticosteroids are antiinflammatory drugs similar to natural corticosteroid hormones produced by the adrenal cortex  Tx with these agents improves symptoms of asthma, allergic rhinitis, eczema, and rheumatoid arthritis  Corticosteroids inhibit late phase allergic reactions (including late asthmatic response to antigen challenge) by various mechanisms, eg., reduced 1) number of mast cells lining surfaces of airway mucosal cells; 2) chemotaxis and activation of eosinophils; and 3) cytokine production by eosinophils, monocytes, mast cells, and lymphocytes Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids (2)  Corticosteroids taken regularly reduce bronchial reactivity, enhance airway quality, & decrease severity & frequency of asthma attacks  However, corticosteroids do not directly relax smooth muscle  Would be only ones needed to treat asthma if their adverse effects were not so pronounced Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids (3) Commonly used agents  prednisone,  methylprednisone,  beclomethasone,  flunisolide,  budesonide, and  mometasone Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids: Clinical Uses ď&#x201A;§ Corticosteroids have marked adverse effects on nonrespiratory systems, so inhalation (maintenance therapy in asthma, via inhaler) or intranasal (in allergy, as nasal spray) route is preferred ď&#x201A;§ Intranasal corticosteroids relieve stuffy nose, nasal irritation, and other discomforts

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids: Clinical Uses (2)  Corticosteroids inhaled by mouth effectively prevent asthma attacks  Regular doses of aerosol agents are smaller than doses used in pill form  Smaller, regular doses reduce side effect risk and may eliminate a need for oral steroids  Oral prednisone or IV methylprednisone is used only when pts are insensitive to inhaled drugs or need urgent treatment for severe asthma attacks Marc Imhotep Cray, M.D.

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ď&#x201A;§ Spacers (chambers) can be attached to metered-dose inhalers to reduce velocity & particle size of drug; amount of drug reaching lungs is maximized, and quantity of drug deposited in mouth is minimized ď&#x201A;§ Spacers are crucial for Tx with corticosteroids, which have many adverse effects

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-19

Corticosteroids: Clinical Uses (3)

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-18

Corticosteroid Actions in Bronchial Asthma Illustrated

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Corticosteroids: Adverse Effects  Taking corticosteroids orally (prednisone) and intravenously (methylprednisone) can cause unwanted side effects  Short-term use (days) of prednisone can lead to increased appetite, wt. gain, diarrhea, headache, mood changes & insomnia, and possibly hyperglycemia & hypertension  Cessation of short term corticosteroid use or taking smaller doses of these agents usually minimizes or eliminates effects      

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids: Adverse Effects (2)  Adverse effects that accompany long-term (months to years) oral and IV therapy are    

suppressed immune system, increased cholesterol levels, and rapid wt. gain Long-term use may also promote osteoporosis, cataracts, and thinning of the skin

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Corticosteroids: Adverse Effects (3) ď&#x201A;§ Efforts to develop safer corticosteroids with antiinflammatory properties but lacking adverse effects are ongoing ď&#x201A;§ Lipophilic steroids, such as beclomethasone, flunisolide, budesonide, and mometasone, have a strong safety profile and are almost devoid of orally precipitated systemic effects

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-20

Corticosteroids: Adverse Effects Illustrated

Principles of Drug Therapy

(4) Anti-inflammatory Agents: Leukotriene Antagonists  Leukotrienes are arachidonic acid derivatives involved in inflammatory processes including asthma and anaphylaxis  The enzyme 5-lipoxygenase catalyzes synthesis of arachidonic acid into unstable intermediates>>> which are converted into leukotrienes  A number of airway cells (including mast cells, macrophages, eosinophils, and basophils) synthesize, store, & secrete several subtypes of proinflammatory leukotrienes  Leukotriene B4 (LTB4) attracts additional leukocytes, and LTC4 and LTD4 increase bronchial reactivity, bronchoconstriction, and secretion of mucus Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Leukotriene Antagonists (2)  Evidence that inhaled leukotrienes increase bronchial reactivity and that antigen challenge in sensitized airways augments leukotriene synthesis…  …supports a role for these mediators in asthma and a rationale for development of drugs that block leukotriene or 5-lipoxygenase action

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-21

Leukotrienes Synthesis Illustrated

Principles of Drug Therapy

Leukotriene Antagonists (4) Efforts to develop drugs that disrupt proinflammatory actions of leukotrienes produced 2 types of drugs: 1) 5-lipoxygenase inhibitors and 2) leukotriene antagonists

 Zileuton reduces leukotriene synthesis rate by blocking 5-lipoxygenase  Zafirlukast and montelukast, LTD4 antagonists, block leukotriene receptors and prevent these mediators from causing an asthmatic response  When taken regularly, these drugs work as well as inhaled corticosteroids in reducing frequency of asthma attacks  However, leukotriene antagonists are less successful for relieving symptoms, reducing bronchial reactivity, and improving airway quality Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Leukotriene Antagonists (5) ď&#x201A;§ These drugs are effective and safe when taken orally, an advantage compared with inhaled corticosteroids ď&#x201A;§ Strong safety profile and excellent oral activity account for popularity of leukotriene antagonists for children ď&#x201A;§ Leukotriene antagonists also reduce responses in aspirininduced asthma, a disorder affecting nearly 10% of patients with asthma Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-22

Leukotriene Antagonists MOA Illustrated

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Management of Acute Asthmatic Attack

Marc Imhotep Cray, M.D.

Raffa RB etal. Netter's Illustrated Pharmacology, Updated Ed. Figure 7-15

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The National Asthma Education and Prevention Program 1997 Guidelines (Updated) RECOMMENDATIONS FOR PHARMACOLOGIC MANAGEMENT OF ASTHMA IN ADULTS AND CHILDREN OLDER THAN 5 Asthma Severity

Symptom Frequency

Medications

Mild intermittent

<2 days/week, <2 nights/month

No regular therapy; short-acting β2 –agonists as needed for symptom relief

Mild persistent

>2 per week but <once per day >2 nights/month

Low-dose inhaled glucocorticoids. Alternate: cromolyn, nedocromil, leukotriene modifier, or sustained release theophylline

Moderate persistent

Daily, >1 night/week

Low- to medium-dose glucocorticoids and long-acting inhaled β2 agonists. Alternate: leukotriene modifier or theophylline

Severe persistent

Continual during day, frequent at night

High-dose glucocorticoids and long-acting inhaled β2 -agonist and (if needed) systemic glucocorticoids. Consider omalizumab for allergy sufferers

Ressel GW, Centers for Disease Control and Prevention, National Asthma Education and Prevention Program. NAEPP updates guidelines for the diagnosis and management of asthma. Am Fam Physician . 2003;68:169–70. Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Case Summary Summary: An 8-year-old boy with asthma is prescribed an albuterol inhaler.



Mechanism of action of albuterol: β2 -Adrenoceptor agonist in bronchial smooth muscle causes smooth muscle relaxation, inhibits the release of mediators from mast cells, and stimulates mucociliary clearance



Most common side effects of albuterol: Skeletal muscle tremor, tachycardia, and cough

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Medications for long-term control of asthma: Inhaled corticosteroids, long acting β2 -adrenoceptor agonist, cromolyn, or nedocromil; secondline agents include oral theophylline, leukotriene inhibitors, or systemic corticosteroids

Marc Imhotep Cray, M.D.

Principles of Drug Therapy

Further study: Pharmacology Course Website References: Drazen JM, O’Byrne PM. Risks of long-acting beta-agonists in achieving asthma control. N Engl J Med .2009;360:1671. Lim KG. Management of persistent symptoms in patients with asthma. Mayo Clin Proc . 2002;77:1333–8. Panettieri RA, In the Clinic. Asthma. Ann Internal Med . 2007;146:ITC6–16. Ressel GW, Centers for Disease Control and Prevention, National Asthma Education and Prevention Program. NAEPP updates guidelines for the diagnosis and management of asthma. Am Fam Physician . 2003;68:169–70. Salpeter SR, Wall AJ, Buckley NS. Long-acting beta-agonists with and without inhaled corticosteroids and catastrophic asthma events. Am J Med . 2010; 123:322. Marc Imhotep Cray, M.D.