nrsg351 respiratory agents in asthma, copd, cough, cold and allergy

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Trigger Mechanism

Respiratory infection Inflammatory response produces bronchial hyperresponsiveness; IgE induction by some viruses; eosinophil activation by some viruses

Allergens Classic allergic pathway

Environment / occupational stimuli

Epithelial damage; inflammation

Emotions Excess parasympathetic activation of bronchial tissue

Exercise Heat loss and water loss from airways;

Drugs , foods Sulfite preservatives stimulate inflammation; aspirin and NSAIDS inhibit cyclooxygenase

http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/

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Asthma COPD

Early onset; family history Mid-life onset

Variable or seasonal symptoms; symptoms worse at night or early morning

Slowly progressing symptoms

Associated with allergies / rhinitis; eczema; dermatitis

History of smoking

REVERSIBLE airway obstruction IRREVERSIBLE (or variably reversible) airway obstruction

Goals of therapy in acute asthma

• Rapid reversal of airway obstruction

• Correction of significant hypoxemia

• Restoration of normal lung function

• Reduction of asthma symptoms

• Development of a plan for future attacks

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Drugs used to treat asthma

• Bronchodilators– Beta 2 agonists– Anticholinergics

• Antiinflammatory agents– Corticosteroids– Leukotriene modifiers– Mast cell stabilizers– Monoclonal antibodies

Agents can be used systemically or via inhalation

Beta-2 agonistsAlbuterol (Ventolin® Proventil® Accuneb® )Levalbuterol (Xopenex®)

Fluticasone / salmeterol (Advair®)Mometasone furoate / formoterol fumarate (Dulera®)

Formoterol fumarate (Foradil®)

Pharmacology (Mechanism of action)

Stimulates b-2 receptors

Activates adenylate cyclase and increases cAMP

cAMP produces relaxation of smooth muscle and bronchodilation

Adverse Effects Pharmacokinetics

Short-acting

Long-acting

Beta-2 agonists

• Contraindications

– Allergy

– Uncontrolled cardiac dysrhythmias (especially tachyarrhythmias)

Beta-2 agonists

• Adverse effects – serious– Urticaria

– Arrhythmia, QT prolongation, angina, hypokalemia

– Paradoxical bronchospasm

• Adverse effects – common– Nervousness, tremor, palpitations, tachycardia

– Bad taste

– Throat irritation

MethylxanthinesTheophylline (Theo-Dur®)Aminophylline (various)


Block phosphodiesterase enzymes, which leads to increased cAMP in bronchial tissue

Increased cAMP leads to smooth muscle relaxation


Anticholinergics Ipratropium bromide (Atrovent®)Tiotropium bromide (Spiriva Handihaler®)


Blocks post ganglionic vagal pathways

Decreased vagal tone produces bronchodilation


N3HCCH

CH3

CH3

O C

O

CH

OH

Br-

Ipratropium bromide

Anticholinergics

• Contraindicated in– Allergy to atropine or components of the

preparation

– Myasthenia gravis, narrow angle glaucoma

– Tiotropium should not be used with ipratropium

• Adverse effects – common– Nausea, vomiting, diarrhea

– Nasal congestion, dyspnea

Corticosteroids Beclomethasone (Beclovent® Vanceril® QVAR80® )Budesonide (Pulmicort®)

Fluticasone / salmeterol (Advair®)

Triamcinolone acetonide (Azmacort®)


Inhibits neutrophil and eosinophil invasion

Inhibits synthesis of prostaglandins, histamines and leukotrienes


http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213836.htm

http://www.fda.gov/Drugs/DrugSafety/ucm251512.htm

http://www.fda.gov/Drugs/DrugSafety/ucm251512.htm

Corticosteroids

• Adverse effects – serious (most are rare when inhaled)– Adrenal suppression– Osteoporosis / growth suppression in children– Bronchospasm– Peptic ulcers

• Adverse effects – common – Sinusitis, rhinitis, hoarseness– Headache, nausea, diarrhea– Oral candidiasis

Leukotriene receptor antagonistsMontelukast (Singulair®)Zileuton (Zyflo®)Zafirlukast (Accolate®)Pharmacology (Mechanism of action)

blocks leukotriene receptors

Prevents leukotrienes from participating in inflammatory responses


Arachidonic acid

Lipoxygenase products

lipoxygenase

LTC4 and LTD4

TXA2COX

Bronchoconstrictionand inflammation

Montelukast, zafirlukast(receptor antagonists) act here

Zileuton act here

Leukotriene modifiers

• Adverse effects – serious– Angioedema– Anaphylaxis – Churg-Strauss syndrome (coincidental?)

• Adverse effects – common– Flu like symptoms (cough, fatigue, headache,

abdominal pain)

– Adverse effects have not been well documented and these agents are believed to be very safe

Mast Cell StabilizersCromolyn sodium (Nasalcrom® , Intal®)


Prevent the release of histamine and inflammatory mediators by mast cells by stabilizing their membranes;

Reduced release of inflammatory and bronchoconstrictive substances reduces bronchoconstriction


Monoclonal antibody preparationsOmalizumab (Xolair®)


inhibits IgE binding to receptors on mast cells and basophils, preventing degranulation

Reduces release of allergic response mediators


Upper Respiratory Medications

• Antihistamines, decongestants and other nasal agents

• Common, available OTC and Rx

• Alone and in combination

• Use in children is discouraged

Antihistamines1st generation OTC 2nd generation OTCDimenhydrinate (Dramamine ®) Cetirizine (Zyrtec ®)Diphenhydramine HCl (Benadryl®) loratidine (Claritin®, Chlorpheniramine (Chlor-Trimeton®) des-loratidine (Clarinex®) fexofenadine (Allegra®, Allegra-D®) Pharmacology (Mechanism of action)

Blocks H1 receptors

Histamine cannot bind, produce responses associated with allergic responses

(No effect to decrease histamine release)


DecongestantsTopical (intranasal) OTC Systemic OTCOxymetazoline (Afrin®, Allerest®) Pseudoephedrine (Sudafed®)Phenylephrine (Neo-synephrine®)Xylometazoline (Otrivin ®)


a1 stimulation produces vasoconstriction

Vasoconstriction leads to decreased swelling, edema and stuffy nasal passages


Decongestants

• Contraindicated in patients with – Hypertension or CAD– Do not use concurrently with TCAs, beta

blockers, MAOIs

• Adverse effects include– Tachycardia, increased BP, arrhythmias– Restlessness, insomnia, anxiety, tremor– Rebound phenomenon

Intranasal antiinflammatory agentsCorticosteroids - RxTriamcinolone acetonide (Nasacort ®) Budesonide (Rhinocort®) Fluticasone (Flonase®) Pharmacology (Mechanism of action)

Decreases the release of inflammatory mediators


Agents used to treat cough

• Antitussives – prevent coughing

• Expectorants – thin mucus secretions, making it easier to cough

ExpectorantsGuaifenesin (Robitussin, Mucinex) Pharmacology (Mechanism of action)

Decreases the viscosity of mucus to aid in its elimination


AntitussivesDextromethorphan (Robitussin-DM, Mucinex-DM, Delsym) Pharmacology (Mechanism of action)

Depresses medullary cough center


dextromethorphan

Levophoranol (Levo-Dromoran)

Antitussives – Rx codeine containing and derivatives(Tussionex, Tussi-organidin) Pharmacology (Mechanism of action)

Depresses medullary cough center


Antitussives – RxNon-codeine derivatives

Benzonatate (Tessalon Perles) Pharmacology (Mechanism of action)

Local anesthetic action on the respiratory passageways and stretch receptors of the lung; decreases cough reflex


nrsg351 respiratory agents in asthma, copd, cough, cold and allergy

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