By Linda Self

Key Terms1.Ventilation2.Perfusion3.Diffusion4.Pulmonary Circulation5.Surfactant6.pneumocytes

Asthma—inflammation, hyperreactivity,

and bronchoconstriction GERD may cause

microaspiration/resultant nighttime cough

Antiasthma medications can also exacerbate GERD

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

Bronchoconstriction Inflammation Mucosal edema Excessive mucous

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

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

Bronchodilators and anti-inflammatories

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 <1x/day or >2 nights/month. In those >5 years old, use inhaled corticosteroid, leukotriene modifier, Intal (cromolyn), or sustained release theophylline

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

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

Step 4— Children less than 5 yo—same as for

adults and older children

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

Cautious use in hypertension and cardiac disease

Selective beta 2 agonists by inhalation are drugs of choice

Epinephrine sc in acute bronchoconstriction

Proventil (albuterol) Xopenex (levalbuterol)

Treatment of first choice to relieve acute asthma

Aerosol or nebulization May be given by MDI Overuse will diminish their

bronchodilating effects>>>>tolerance

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.

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

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)

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

Contraindicated in acute gastritis and PUD

Second line Narrow therapeutic window—

therapeutic range is 5-15 mcg/mLh Multiple drug interactions

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

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

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

For inhalation: Beclovent—beclomethasone Pulmicor—budesonide Aerobid—flunisolide Flovent—fluticasone Azmacort—triamcinolone Most inhaled steroids are being

reformulated with HFA

Systemic use: prednisone, methylprednisolone, and hydrocortisone

In acute, severe asthma—a systemic corticosteroid may be indicated when inhaled beta 2 agonists are ineffective

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

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

Injured cell

Arachidonic acid XXXX Lipooxygenase

Leukotrienes XXXX Bronchi, WBCs

Bronchoconstriction

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

exposure

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

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

Allergic rhinitis Anaphylaxis Allergic conjunctivitis Drug allergies Transfusions of blood products Dermatologic conditions Nonallergic such as motion sickness,

nausea and vomiting, sleep

Caution in pregnancy BPH Bladder neck obstruction Narrow angle glaucoma

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

Selective or nonsedating Do not cross blood brain barrierExamples: Astelin (azelastine) Allegra (fexofenadine) Claritin (loratadine) Clarinex (desloratadine) Zyrtec Xyzal

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

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

Liquefy respiratory secretions Guiafenesin

By inhalation to liquefy mucous Mucomyst (acetylcysteine) May be used in treating

acetaminophen overdose

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

1. Name two beta adrenergic bronchodilators

2. Name an inhaled steroid3. Give an example of a leukotriene modifier4. Name a mast cell stabilizer5. Name a common infection after frequent

use of an inhaled steroid6. Name a first generation H1 receptor

antagonist

7. Name a second generation H1 receptor antagonist.

8. Name an H2 receptor antagonist.