Drugs affecting the respiratory system
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Drugs affecting the Respiratory System. By Linda Self. Respiratory System. Key Terms Ventilation Perfusion Diffusion Pulmonary Circulation Surfactant pneumocytes. Drugs for Asthma and Other Bronchoconstrictive Disorders. Asthma—inflammation, hyperreactivity, and bronchoconstriction

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Drugs affecting the respiratory system

Drugs affecting the Respiratory System

By Linda Self


Respiratory system

Respiratory System

  • Key Terms

  • Ventilation

  • Perfusion

  • Diffusion

  • Pulmonary Circulation

  • Surfactant

  • pneumocytes


Drugs for asthma and other bronchoconstrictive disorders

Drugs for Asthma and Other Bronchoconstrictive Disorders

Asthma—inflammation, hyperreactivity,

and bronchoconstriction

GERD may cause microaspiration/resultant nighttime cough

Antiasthma medications can also exacerbate GERD


Asthma

Asthma

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


Asthma1

Asthma

Bronchoconstriction

Inflammation

Mucosal edema

Excessive mucous


Pathophysiology of asthma

Pathophysiology of Asthma

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


Chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease

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


Drug therapy

Drug Therapy

Bronchodilators and anti-inflammatories


Categories of asthma

Categories of Asthma

  • 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


Categories of asthma cont

Categories of Asthma cont.

  • 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


Asthma2

Asthma

  • 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


Asthma3

Asthma

Step 4—

Children less than 5 yo—same as for adults and older children


Bronchodilators

Bronchodilators

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


Bronchodilators adrenergics

Bronchodilators--adrenergics

Cautious use in hypertension and cardiac disease

Selective beta 2 agonists by inhalation are drugs of choice

Epinephrine sc in acute bronchoconstriction


Short acting bronchodilators

Short acting bronchodilators

Proventil (albuterol)

Xopenex (levalbuterol)


Short acting bronchodilators1

Short Acting Bronchodilators

Treatment of first choice to relieve acute asthma

Aerosol or nebulization

May be given by MDI

Overuse will diminish their bronchodilating effects>>>>tolerance


Other bronchodilators

Other bronchodilators

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.


Other bronchodilators1

Other bronchodilators

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


Anticholinergics

Anticholinergics

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)


Xanthines

Xanthines

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


Xanthines1

Xanthines

Contraindicated in acute gastritis and PUD

Second line

Narrow therapeutic window—therapeutic range is 5-15 mcg/mLh

Multiple drug interactions


Anti inflammatory agents

Anti-Inflammatory Agents

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


Corticosteroids

Corticosteroids

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


Steroids

Steroids

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


Steroids1

Steroids

For inhalation:

Beclovent—beclomethasone

Pulmicor—budesonide

Aerobid—flunisolide

Flovent—fluticasone

Azmacort—triamcinolone

Most inhaled steroids are being reformulated with HFA


Steroids2

Steroids

Systemic use: prednisone, methylprednisolone, and hydrocortisone

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


Leukotriene modifiers

Leukotriene Modifiers

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


Leukotriene modifier drugs

Leukotriene Modifier Drugs

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


Leukotriene modifiers1

Leukotriene Modifiers

  • Injured cell

  • Arachidonic acid

  • XXXX

  • Lipooxygenase

  • Leukotrienes

  • XXXX

  • Bronchi, WBCs

  • Bronchoconstriction


Leukotriene modifier drugs1

Leukotriene Modifier Drugs

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


Mast cell stabilizers

Mast Cell Stabilizers

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


Immunosuppressant monoclonal antibody

Immunosuppressant Monoclonal Antibody

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


Antihistamines and allergic disorders

Antihistamines and Allergic Disorders

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


Antihistamines

Antihistamines

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


Antihistamines1

Antihistamines

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


Allergic reactions

Allergic Reactions

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.


Types of responses to cell mediated invasion

Types of Responses to Cell-Mediated Invasion

  • 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


Allergic reactions1

Allergic Reactions

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


Allergic reactions2

Allergic Reactions

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


Type iv hypersensitivity

Type IV Hypersensitivity

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


Allergic rhinitis

Allergic Rhinitis

  • 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


Intranasal drugs for allergic rhinitis

Intranasal Drugs for Allergic Rhinitis

Atrovent nasal spray

Beconase (beclomethasone)

Rhinocort (budesonide)

Flonase (fluticasone)

Nasonex (mometasone)

Nasalcrom (a mast cell stabilizer)


Allergic contact dermatitis

Allergic Contact Dermatitis

Type IV hypersensitivity reaction

Poison ivy an example

Usually occurs >24h after re-exposure


Other reactions

Other reactions

  • 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


Antihistamines2

Antihistamines

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


Indications for use

Indications for Use

Allergic rhinitis

Anaphylaxis

Allergic conjunctivitis

Drug allergies

Transfusions of blood products

Dermatologic conditions

Nonallergic such as motion sickness, nausea and vomiting, sleep


Precautions

Precautions

Caution in pregnancy

BPH

Bladder neck obstruction

Narrow angle glaucoma


First generation h1 receptor antagonists

First Generation H1 Receptor Antagonists

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)


Second generation h1 receptor antagonists

Second Generation H1 Receptor Antagonists

Selective or nonsedating

Do not cross blood brain barrier

Examples:

Astelin (azelastine)

Allegra (fexofenadine)

Claritin (loratadine)

Clarinex (desloratadine)

Zyrtec

Xyzal


Nasal decongestants

Nasal Decongestants

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


Antitussives

Antitussives

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


Expectorants

Expectorants

Liquefy respiratory secretions

Guiafenesin


Mucolytics

Mucolytics

By inhalation to liquefy mucous

Mucomyst (acetylcysteine)

May be used in treating acetaminophen overdose


Cold remedies

Cold Remedies

  • 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


Review

Review

Name two beta adrenergic bronchodilators

Name an inhaled steroid

Give an example of a leukotriene modifier

Name a mast cell stabilizer

Name a common infection after frequent use of an inhaled steroid

Name a first generation H1 receptor antagonist

Name a second generation H1 receptor antagonist.

Name an H2 receptor antagonist.


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