1. By Linda Self

2.  Key Terms 1. Ventilation 2. Perfusion 3. Diffusion 4. Pulmonary Circulation 5. Surfactant 6. pneumocytes

3.  Asthma—inflammation, hyperreactivity,  and bronchoconstriction  GERD may cause microaspiration/resultant nighttime cough  Antiasthma medications can also exacerbate GERD

4.  May be triggered by viruses  Irritants  Allergens  Can develop at any age  Seen more often in children who are exposed to airway irritants during infancy

5.  Bronchoconstriction  Inflammation  Mucosal edema  Excessive mucous

6.  Mast cells  Chemical mediators such as histamine, prostaglandins, acetylcholine, cGMP, interleukins, leukotrienes are released when triggered. Mobilization of eosinophils. All cause movement of fluid and proteins into tissues.  Bronchoconstrictive substances antagonized by cAMP

7.  Combination of chronic bronchitis and emphysema  Bronchoconstriction and inflammation are more constant, less reversibility  Anatomic and physiologic changes occur over years  Leads to increasing dyspnea and activity intolerance

8.  Bronchodilators and anti-inflammatories

9.  Step 1-Mild Intermittent—symptoms 2 days/week or less or 2 nights/month or less. No daily medication needed; treat with inhaled beta2 agonist  Step 2-Mild persistent—symptoms >2/week but 2 nights/month. In those >5 years old, use inhaled corticosteroid, leukotriene modifier, Intal (cromolyn), or sustained release theophylline

10.  Step 2—Mild persistent  Children 5 years and younger—inhaled corticosteroid by nebulizer of MDI with a holding chamber. Can also use leukotriene modifier or Intal by nebulizer  Step 3—Moderate persistent. Symptoms daily and > one night per week.  Older than 5yo—low to med. Dose corticosteroid and long acting beta 2 agonist. Alternatives p. 714

11.  Step 3—  Children < 5 yo: low dose inhaled corticosteroid and a long acting beta 2 agonist or medium dose inhaled corticosteroid  Step 4—Severe persistent—symptoms continual during daytime and frequently at night.  >5yo—high dose inhaled corticosteroid, long acting beta 2 agonist; intermittent admin. of oral corticosteroids

12.  Step 4—  Children less than 5 yo—same as for adults and older children

13.  Adrenergics—stimulate beta 2 receptors in smooth muscle of bronchi and bronchioles  Receptors stimulate cAMP =bronchodilation  Cardiac stimulation is an adverse effect of these medications

14.  Cautious use in hypertension and cardiac disease  Selective beta 2 agonists by inhalation are drugs of choice  Epinephrine sc in acute bronchoconstriction

15.  Proventil (albuterol)  Xopenex (levalbuterol)

16.  Treatment of first choice to relieve acute asthma  Aerosol or nebulization  May be given by MDI  Overuse will diminish their bronchodilating effects>>>>tolerance

17.  Foradil (formoterol) and Serevent (salmeterol) are long acting beta 2 adrenergic agonists used only for prophylaxis. Black box warning on Serevent—use in deteriorating asthma can be life-threatening  Alupent (metaproterenol)—intermediate acting. Useful in exercise induced asthma, tx acute bronchospasm.

18.  Brethine (terbutaline)—selective beta 2 adrenergic agonist that is a long-acting bronchodilator  When given subq, loses selectivity  Also used to decrease premature uterine contractions during pregnancy

19.  Block the action of acetylcholine in bronchial smooth muscle when given by inhalation  Action reduces intracellular guanosine monophosphate (GMP) which is a bronchoconstrictive substance  Atrovent (ipratropium)—caution in BPH, narrow-angle glaucoma  Spiriva (tiotropium)

20.  Theophylline  Mechanism of action unclear  Bronchodilate, inhibit pulmonary edema, increase action of cilia, strengthen diaphragmatic contractions, over-all anti- inflammatory action  Increases CO, causes peripheral vasodilation, mild diuresis, stimulates CNS

21.  Contraindicated in acute gastritis and PUD  Second line  Narrow therapeutic window—therapeutic range is 5-15 mcg/mLh  Multiple drug interactions

22.  Suppress inflammation by inhibiting movement of fluid and protein into tissues; migration and function of neutrophils and eosinophils, synthesis of histamine in mast cells, and production of proinflammatory substances  Benefits: decreased mucous secretion, decreased edema and reduced reactivity

23.  Second action is to increase the number and sensitivity of beta 2 adrenergic receptors  Can be given PO or IV  Pulmonary function usually improves within 6-8 hours  Continue drugs for 7-10 days

24.  Fewer long term side effects if inhaled  End-stage COPD may become steroid dependent  In asthma, systemic steroids generally are used only temporarily  Taper high dose oral steroids to avoid hypothalamic-pituitary axis suppression

25.  For inhalation:  Beclovent—beclomethasone  Pulmicor—budesonide  Aerobid—flunisolide  Flovent—fluticasone  Azmacort—triamcinolone  Most inhaled steroids are being reformulated with HFA

26.  Systemic use: prednisone, methylprednisolone, and hydrocortisone  In acute, severe asthma—a systemic corticosteroid may be indicated when inhaled beta 2 agonists are ineffective

27.  Leukotrienes are strong chemical mediators of bronchoconstriction and inflammation  Increase mucous secretion and mucosal edema  Formed by the lipoxygenase pathway of arachidonic acid metabolism in response to cellular injury  Are release more slowly than histamine

28.  Developed to counteract the effects of leukotrienes  Indicated for long term treatment of asthma in adults and children  Prevent attacks induced by some allergens, exercise, cold air, hyperventilation, irritants and ASA/NSAIDs  Not useful in acute attacks

29.  Injured cell  Arachidonic acid  XXXX  Lipooxygenase  Leukotrienes  XXXX  Bronchi, WBCs  Bronchoconstriction

30.  Singulair (montelukast) and Accolate (zafirlukast) are leukotriene receptor antagonists  Can be used in combination with bronchodilators and corticosteroids  Less effective than low doses of inhaled steroids  Should not be used during lactation  Can cause HA, nausea, diarrhea, other

31.  Intal (cromolyn)  Tilade (nedocromil)  Prevent release of bronchoconstrictive and inflammatory substances when mast cells are confronted with allergens and other stimuli  Prophylaxis only  Inhalation, nebulizer or MDI, nasal spray as well

32.  Xolair (omalizumab) works by binding to IgE, blocking receptors on surfaces of mast cells and basophils  Prevents release of chemical mediators of allergic reactions  Adjunctive therapy  Can cause life-threatening anaphylaxis

33.  Histamine is the first chemical mediator released in immune and inflammatory responses  Concentrated in skin, mucosal surfaces of eyes, nose, lungs, CNS and GI tract  Located in mast cells and basophils  Interacts with histamine receptors on target organs called H1 and H2

34.  H1 receptors are located mainly on smooth muscle cells in blood vessels and the respiratory and GI tracts  H1 binding causes: pruritus, flushing, increased mucous production, increased permeability of veins—edema, contraction of smooth muscle in bronchi>>bronchoconstriction and cough

35.  With H2 receptor stimulation, main effects are increased secretion of gastric acid and pepsin, decreased immunologic and proinflammatory reactions, increased rate and force of myocardial contraction

36.  Are exaggerated responses by the immune sysem that produce tissue injury and possible serious disease  Allergic reactions may result from specific antibodies, sensitized T lymphocytes, or both, formed durng exposure to an antigen.

37.  Type I—immediate hypersensitivity, IgE induced response triggered by the interaction of antigen with antigen- specific IgE bound on mast cells  Anaphylaxis is an example  Does not occur on first exposure to an antigen  Can develop profound vasodilation resulting in hypotension, laryngeal edema, bronchoconstriction

38.  Type II—IgG or IgM mediated which generate direct damage to cell surfaces. Examples include: blood transfusion reactions, hemolytic disease of newborns, hypersensitivity reactions to drugs such as heparin or penicillin

39.  Type III is an IgG or IgM mediated reaction characterized by formation of antigen-antibody complexes that induce inflammatory reaction in tissues. Prototype is Serum Sickness.  Immune response can occur following antitoxin administration, pcn or sulfa drugs

40.  Delayed hypersensitivity  Cell mediated response where sensitized T lymphocytes react with an antigen to cause inflammation, release of lymphokines, direct cytotoxicity or both  Classic examples are tuberculin test, contact dermatitis and some graft rejections

41.  IgE mediated  Inflammation of nasal mucosa caused by a hypersensitivity reaction to inhaled allergens  Presents with itching of throat, eyes and ears  Seasonal and perennial  Can lead to chronic fatigue, difficulty sleeping, sinus infections, postnasal drip, cough and headache

42.  Atrovent nasal spray  Beconase (beclomethasone)  Rhinocort (budesonide)  Flonase (fluticasone)  Nasonex (mometasone)  Nasalcrom (a mast cell stabilizer)

43.  Type IV hypersensitivity reaction  Poison ivy an example  Usually occurs >24h after re-exposure

44.  Allergic food reactions—result from ingestion of a protein  Most common food allergy is shellfish, others include milk, eggs, peanuts  Allergic drug reactions—unpredictable, may occur 7-10 days after initial exposure  Pseudoallergic drug reactions— resemble immune responses but do not produce antibodies, i.e. anaphylactoid

45.  Inhibit smooth muscle constriction in blood vessels and the respiratory and GI tracts  Decrease capillary permeability  Decrease salivation and tear formation  Act by binding with the histamine receptor

46.  Allergic rhinitis  Anaphylaxis  Allergic conjunctivitis  Drug allergies  Transfusions of blood products  Dermatologic conditions  Nonallergic such as motion sickness, nausea and vomiting, sleep

47.  Caution in pregnancy  BPH  Bladder neck obstruction  Narrow angle glaucoma

48.  Bind to central and peripheral receptors  Can cause CNS depression or stimulation  Have substantial anticholinergic effects Examples:  Chlor-Trimeton (chlorpheniramine)  Benadryl (diphenhydramine)  Vistaril (hydroxyzine)  Phenergan (promethazine)

49.  Selective or nonsedating  Do not cross blood brain barrier Examples:  Astelin (azelastine)  Allegra (fexofenadine)  Claritin (loratadine)  Clarinex (desloratadine)  Zyrtec  Xyzal

50.  Relieve nasal obstruction and discharge  Adrenergic  Rebound nasal swelling called “rhinitis medicamentosa”  Afrin  Sudafed (pseudoephedrine)  Contraindicated in severe hypertension, CAD, narrow angle glaucoma, TCAs or MAOIs

51.  Suppress cough by depressing cough center in medulla or by increasing flow of saliva  For dry, hacking, non-productive cough  Not recommended in children and adolescents  Codeine, hydrocodone  dextromethorphan

52.  Liquefy respiratory secretions  Guiafenesin

53.  By inhalation to liquefy mucous  Mucomyst (acetylcysteine)  May be used in treating acetaminophen overdose

54.  Contain antihistamine, decongestant and an analgesic  Chlorpheniramine, pseudoephedrine, acetaminophen, dextromethorphan and guiafenesin  Decongestants can cause stasis of secretions  PM contains antihistamine  Tamiflu can be used to limit spread of virus in respiratory tract

55. 1. Name two beta adrenergic bronchodilators 2. Name an inhaled steroid 3. Give an example of a leukotriene modifier 4. Name a mast cell stabilizer 5. Name a common infection after frequent use of an inhaled steroid 6. Name a first generation H1 receptor antagonist 7. Name a second generation H1 receptor antagonist. 8. Name an H2 receptor antagonist.